Showing posts with label Pharmaceuticals. Show all posts
Showing posts with label Pharmaceuticals. Show all posts

Tuesday, December 31, 2013

Grading Pharma In 2013: Gilead's hepatitis C collaboration with Bristol had ethical issues

Grading Pharma In 2013: 16 Drug Companies Ranked

I gave one A+, to Bristol-Myers Squibb, based on its overall performance and its pioneering development of cancer drugs that work by priming the immune system. Gilead Sciences would have gotten one two were it not for the ethical issues surrounding its stopped collaboration with Bristol in hepatitis C, which I think hurt some patients. I am giving no Ds or Fs. There were no big drug disasters on a par with the recall of Merck’s Vioxx or Pfizer’s Bextra this year. Not even close. 
Companies are sorted by the letter grade I gave them, and, where there was a tie, by stock performance. Let me know what I got right – and what I got wrong. 
The Best Drug Companies 
1. Bristol-Myers Squibb CompanyMarket capitalization: $87 billionStock appreciation: +61.4%Grade: A+ 
Sure, the big-cap biotechs delivered better stock performance. But Big Pharmas don’t trade like this, and Bristol’s transformation, started under James Cornelius and continuing under current chief Lamberto Andreotti, has simply been amazing. (Former R&D head Elliot Sigal deserves credit, too.) Bristol is leading the way when it comes to cancer immunotherapy, which Science Magazine named as the breakthrough of the year. It’s smartly jettisoning its diabetes business to focus on what is working. And it is a player in hepatitis C............

Continue Reading @ Forbes

Tuesday, December 17, 2013

Investment Commentary - Can Abbvie Trump Gilead's HCV Lead?

Investment Commentary

Analysis: Fight for cheap drugs shifts from AIDS to new hepatitis pills
LONDON (Reuters) - A new battle is looming over access to antiviral medicines in developing countries - this time for treating hepatitis C - more than a decade after a global showdown over the price of AIDS drugs in Africa.

Modern pills being launched in western markets could cure the liver-destroying infection in tens of millions of people from China to Congo, or even eradicate the disease entirely. But that will only happen if the cost falls dramatically.

Express Scripts Pushes Price Competition for Gilead Drug
Express Scripts Holding Co. (ESRX) will pit Gilead Sciences Inc. against AbbVie Inc. and other drugmakers when the new treatments come to market next year or early in 2015. The new hepatitis C pills are projected to be among the biggest pharmaceutical sellers ever. While Gilead’s once-a-day drug may be the easiest to use, Express Scripts might block the pill from reimbursement if the competitors accept lower pricing.

AbbVie Demonstrates 96 percent SVR(12) Phase III Treatment-Experienced Patients with Geno 1 Hepatitis C
AbbVie (NYSE: ABBV) released phase III results for the investigational three direct-acting-antiviral (3D) regimen plus ribavirin in patients with chronic, genotype 1 (GT1) hepatitis C virus (HCV) infection. In the 394-patient SAPPHIRE-II study, 96 percent of patients who previously failed pegylated interferon and ribavirin treatment, including approximately 49 percent of who were prior null responders, achieved sustained virologic response at 12 weeks (SVR12) with the regimen. The majority of patients were GT1a, considered a difficult-to-treat subtype, and the SVR12 rates of GT1a and GT1b were 96 percent and 97 percent, respectively. 

Hep C Price War? Abbvie Vs. Gilead 
An interview given by an executive of Express Scripts (ESRX) created a stir in the industry.
Express Scripts' chief medical officer, Steve Miller, told Bloomberg that the convenience of Sovaldi's one-pill-a-day regimen won't necessarily justify the $84,000 price tag for a 12-week regimen, meaning his company may approve Abbvie's (ABBV) regimen instead of Sovaldi if Abbvie's drug is priced lower.

Can Abbvie Inc (NYSE:ABBV) Trump Gilead Sciences, Inc.'S (NASDAQ:GILD) HCV Lead?
By: Mani
December 17, 2013 11:15 AM

Gilead and Johnson & Johnson (NYSE:JNJ) have established an extraordinarily high cost ceiling with Sovaldi and Olysio ($84,000 and $66,360, respectively, for 12 weeks of treatment).

BMO Capital Markets analyst Alex Arfaei says he does not believe convenience is as important for an 8-12 week treatment regimen that produce a cure compared with, for example, chronic HIV treatment.

AbbVie could price its oral regimen at roughly $60,000 for 12-weeks of treatment, including rebates and discounts (e.g. wholesale acquisition cost, or WAC, of about $80,000 with 25 percent discounts). This should provide a significant discount relative to Gilead's Sovaldi-ledipasvir fixed dose combo (WAC of $84,000 for Sovaldi alone, maybe about $100,000 for the fully distributed cost).

Arfaei noted that these next generation costly regimens will likely be rationed for more advanced HCV patients (with fibrosis or cirrhosis). Moreover, there is a meaningful opportunity for AbbVie's relatively less convenient, but highly effective regimen as a more economic option.

Gilead estimates there are about 4.1 million U.S. patients and another 2.8 million people living with the disease in the European Union. The company says less than half of those patients have been diagnosed, and less than 10 percent has been treated.

The comments from Miller mean that Express Scripts may approve Abbvie's regimen instead of Sovaldi if Abbvie's drug is priced lower. This assumes significance given Express Scripts' is the biggest U.S. drug benefits manager, whose decisions affect about 100 million patients. The company filled 1.5 billion drug prescriptions in 2013, or 38 percent of the total prescriptions in the U.S.

Recently, AbbVie released top-line phase III results for the investigational three direct-acting-antiviral (3-DAA) regimen plus ribavirin (RBV) in patients with chronic, genotype 1 (GT1) hepatitis C virus (HCV).

In the 394-patient study, 96 percent of patients who previously failed pegylated interferon (INF) and RBV treatment, including approximately 49 percent prior null responders, achieved sustained virologic response at 12 weeks (SVR12) with the 12-week regimen.

The majority of patients were GT1a, considered the more difficult-to-treat sub-type, but the regimen were equally effective in both GT1a and GT1b. Virologic relapse or breakthrough was seen in 2 percent of patients receiving the regimen. In addition, the discontinuation rate due to adverse events was 1 percent.

This is the second of six phase-3 trials studying AbbVie's 3-DAA regimen, and the results again confirmed earlier phase-2 studies. Although, this trial did not include patients with cirrhosis, one should see data in those patients from the TURQUOISE-II study expected by January 2014 and that study includes Rx naïve and experienced patients with compensated cirrhosis.

Arfaei said these are the more advanced patients, many of whom are being "warehoused" until the newer regimens are available. This is the greatest unmet need in HCV because many of these patients will need costly liver transplants.

Abbvie's goal is to cure patients as completely as possible and to lift their sustained viral response as high as possible. Notably, AbbVie's regimen is proving to be more or less equal to Gilead' Sovaldi, achieving near-universal cure rates in important trials of patients with the virus' difficult-to-treat genotype 1.

But, as of now, Gilead is years ahead of competitors in treating genotype 2 and 3 patients who constitute more than 15 percent of hepatitis C patients in the U.S. Sovaldi is the only new HCV antiviral to show effectiveness in genotypes 2 and 3.

Nevertheless, the results from the recent studies potentially position AbbVie to be a stiff competitor against Gilead over an effective HCV regimen.

Arfaei forecasts a strong launch for AbbVie's HCV regimen in late 2014/early 2015, with global sales of $950 million in 2015, peaking at about $3 billion in 2018.

Who Is Express Scripts?

Express Scripts Holding Company is a Fortune 100 company as of 2013, the 24th-largest in the United States[2] and is the largest pharmacy benefit management (PBM) organization in the United States, with 2012 revenues of 93.8 billion.[4]

Headquartered in Cool Valley, Missouri in Greater St. Louis, Express Scripts provides integrated pharmacy benefit management services including network-pharmacy claims processing; home delivery pharmacy services; specialty pharmacy benefit management, through its subsidiary Accredo; benefit-design consultation; drug-utilization review; formulary management; and medical and drug data analysis services to manage drug plans for health plans, self-insured employers and government agencies (both as administrator of employee benefits and public assistance programs). One of their largest clients is the United States Department of Defense's Tricare program.[5]

Express Scripts also offers pharmacy benefit management services for workers' compensation insurance programs. The program is accredited by URAC, the nation's largest accrediting body for healthcare.

The company processes pharmaceutical claims annually for members through a network of retail pharmacies. Its own automated pharmacies dispense long-term, chronic medications-like those for diabetes or heart disease-directly to members via home delivery.

Photo Credit

Wednesday, December 11, 2013

Transcript HCV Drugs - Achillion and Idenix presents at Oppenheimer 24th Annual Healthcare Conference

Hello folks,
Both, Achillion and Idenix  presented at Oppenheimer 24th Annual Healthcare Conference, transcripts are available over at Seeking Alpha , below is an excerpt from each presentation.

*Free registration may be required

Achillion Pharmaceuticals, Inc. (ACHN) Oppenheimer 24th Annual Healthcare Conference

Transcript December 11, 2013 1:35 PM ET

View full transcript @ Seeking Alpha
So digging a little deeper into the individual characteristics of the compound in the portfolio, I will start out with ACH-3422 which is the NS5B polymerase inhibitor. For the overall characteristics of ACH-3422, this compound is a novel nucleotide prodrug of a uridine analog and there are certain advantages for selecting a uridine analog over say [Indiscernible] analog. These are advantages come not only in terms of safety but also the high efficacy that is associated with uridine analog.
3422 is highly specific for inhibition of HCV polymerase. It does not inhibit any of the human DNA or RNA polymerase. It is potent and specific for hepatitis C and has demonstrated pan-genotypic activity and a high barrier to resistance as one would anticipate with a nucleotide prodrug. In terms of the pharmacokinetic and metabolism of 3422, we see rapid conversion of prodrug to the monophosphate in microsomes as well as in hepatocytes. The half life of the triphosphate that is generated is/are greater than 24 hours indicating that the drug has potentials for once daily dosing for the preclinical studies that we have done so far. We have completed 14 days safety studies. We have obtained high exposures of the triphosphate in the liver in these studies and so far all the non-clinical data that we have supports our continued development into the clinic. 
If we compare the potency of ACH-3422 to Sofosbuvir across different genotypes, what we see is that the potency of 3422 is at least comparable to or better than the potency of Sofosbuvir. We have compared the potency in genotypes 1a, genotype 2, genotype 3 and genotype 4 and especially in genotype 3, we see a significant improvement in the potency of 3422 as compared to Sofosbuvir.

Continue reading...

Idenix Pharmaceuticals, Inc. at Oppenheimer 24th Annual Healthcare Conference (Transcript)

So, going directly to our lead nucleotide prodrug candidate – this is IDX21437. This is a next generation uridine nucleotide prodrug currently in phase one to clinical testing. This trail has started in Canada. We announced this I think a little over a month ago. And this is a compound that in vitro has demonstrated potent Pangenous [ph] activity. And that we seen very impressive – liver triphosphate levels generated in dibo.  
So, this gives us some confidence that in the human, in the clinical trial – we’ll see nice anti-viral activity. We’ll need to see the data before we can draw any hard conclusions on that but at least we like what we see pre-clinically at this point. 
And, really, that was the basic for discussions around the collaboration with Johnson pharmaceutical around our Helix One and Helix Two combination drug acting in our viral trials. 
So, a little bit about those trials. This is the collaboration with J&J, it’s a non-exclusive HCV collaboration. Helix One is about putting two drugs together. So, our NS5A, inhibitor, Samatasvir and their pro-agent inhibitor’s recently been approved but the generic name for this, simeprevir, and then Helix Two is about putting three drugs together – which is Samatasvir, simprevir and then they have a ritonavir boosted non-nucleotide inhibitor which I’ll just call O55, it’s got a long name, but we’ll just call it O55 for now.

Continue reading..

Source -

Friday, December 6, 2013

What Everybody Ought to Know About Gilead and Johnson's New Hepatitis C Drugs

 Investment Commentary

What Everybody Ought to Know About Gilead and Johnson's New Hepatitis C Drugs

By Todd Campbell
December 6, 2013

A new class of oral drugs for curing hepatits C is hitting the markets this winter, displacing injectible predecessors and ushering in treatments that are shorter and in some cases avoid side-affect riddled interferon.

1. They work better, but not for everyone

This new class of drugs is more effective than the prior-generation injectibles, which include Incivek, now fully controlled by Johnson following Vertex's exit, and Victrelis, made by Merck. Both Gilead and Johnson's new drugs are approved for 12-week treatment courses, far shorter than the 24- to 48-week courses for those predecessors. But both Gilead's and Johnson's drugs don't cure everyone.

In studies, Gilead's sofosbuvir, which will likely be approved as a combination therapy alongside ribavirin, cured roughly 89% of patients with genotype 1, the most common genotype in America. Based on Phase 3 results, Johnson's Olysio cures 84% of cases, but stumbles in patients with the Q80K polymorphism, curing just 58%.

"Given the high frequency of the Q80K polymorphism in the U.S. population and its significant impact on rates of SVR12, DAVP is recommending that all GT1a patients be screened for the Q80K polymorphism. Alternative treatment options should be considered for patients found to be infected with this polymorphic variant," according to the FDA's advisory panel committee recommendation.

That should significantly reduce Olysio's appeal, given that nearly 50% of those with hepatitis C, genotype 1 have Q80K.

2. They come with fewer side effects, but still rely on interferon and ribavirin

The target for all of these drugmakers remains a therapy that is free of side-effect laden interferon and ribavirin. If approved on Dec. 8, Gilead's drug will do away with interferon in treating patients with hepatitis genotypes 2 and 3, but interferon will still be dosed alongside ribavirin for the majority of Americans. Meanwhile, Johnson's Olysio still relies on both interferon and ribavirin.

One of the closest to a truly interferon- and ribavirin-free therapy appears to be Bristol. Bristol's drug daclatasvir is being considered for approval in Japan for use in combination with Bristol's asunaprevir for the tough-to-treat genotype 1b population. That population accounts for 70% of Japanese hepatitis cases. and Bristol's interferon- and ribavirin-free, two-drug combination cleared the disease nearly 85% of the time.

3. Fewer pills, easier regimen

It's not just interferon and ribavirin that make it tough for patients to stick to their drug regimen -- it's the dosing, too. The dosing of multiple drugs and injections with varying treatment schedules makes it hard for patients to adhere to protocols. That can cause them to drop out of treatment, fail to clear the disease, or worse, choose to avoid treatment altogether. As a result, drugmakers are focusing on one-pill solutions.

Unfortunately, current treatments from Gilead and Johnson are multi-pill, which is better, but not ideal. However, one pill treatments should be coming soon. In November, Gilead reported data from a Phase 2 trial showing that 95% of patients were cured by a single, once-daily pill combining sofosbuvir and another Gilead drug, ledipasvir.

4. Increasingly expensive treatment

Some doctors will embrace off-label combinations of sofosbuvir with either daclatasvir or Olysio. Those combinations have shown impressive results in Phase 2 -- so impressive that European regulators have given the nod for compassionate use of daclatasvir, despite Bristol not yet filing for EU approval.

Interim data from a Phase 2 trials combining Olysio with sofosbuvir in patients with liver disease who had failed prior treatment are also remarkable. In that study, the combination delivered a 100% cure rate four weeks following a 12-week course of treatment.

While those combinations offer hope for the most critical cases, they pose a big question for patients and insurers. Analysts peg pricing of Olysio at $67,000 for 12 weeks, and estimates for sofosbuvir are running as high as $100,000 for 12 weeks. For comparison, the cost to treat patients with an interferon and ribavirin combination runs roughly $15,000 to $20,000.

5. Hypercompetitive marketplace

Gilead, Johnson, and Bristol are looking over their shoulders at AbbVie and Merck. Both companies have promising late-stage trials ongoing for treating hepatitis C, with AbbVie guiding for a Q2, 2014 filing with the FDA. In a Phase 3 trial, AbbVie's 3 drug, non-interferon, combination cured 95% of patients with genotype 1. And Merck's MK-5172, combined with MK-8742, produced a cure rate between 96% and 100% in a small Phase 2 trial, prompting the FDA to grant the therapy breakthrough status.

That means investors, patients, and doctors have a lot to consider over the coming year as all these contenders vie for a share of a market Express Scripts thinks will quadruple by the end of 2015.

Friday, November 8, 2013

Bristol-Myers Squibb will stop research to discover new drugs for hepatitis C

Bristol to stop early research in three disease areas

Thu Nov 7, 2013 6:47pm EST

Nov 7 (Reuters) - Bristol-Myers Squibb Co said on Thursday that it would no longer conduct research to discover new drugs for hepatitis C, diabetes and neuroscience, but will increase spending on medicines that harness the immune system to fight cancer.

Company spokeswoman Laura Hortas said the shift in its research and development focus was "slight" and not geared toward cost cuts. But she said 70 to 75 R&D positions will be eliminated, or less than 1 percent of its research workforce.

The company, in an emailed statement, said it will continue with all ongoing late-stage trials of its medicines, including treatments for hepatitis C, and with trials exploring new potential uses of its drugs that are already on the market.

Hortas said early-stage trials of some neuroscience drugs might be scrapped, although Bristol-Myers will continue with one such trial involving the treatment of Alzheimer's disease.

Otherwise, she said ongoing early-stage and mid-stage trials of its many medicines will continue as planned.

The company said it will continue to conduct discovery research, meaning the earliest stages of research before drugs are tested in people, to find new treatments for HIV, hepatitis B, heart failure, oncology, immunoscience and fibrotic diseases.

"We are focusing our R&D organization on delivering the opportunities where the value is greatest to patients," Francis Cuss, Bristol-Myers' chief scientific officer said.

Bristol-Myers is considered a leader in the field of immuno-oncology, in which drugs are used to unlock the immune system to go after cancer cells. Its approved Yervoy treatment for melanoma has provided durable benefits to patients, and the company aims to eventually pair the drug with other therapies that also harness the immune system.

Rival drugmakers are also racing to develop immuno-oncology medicines, which industry analysts expect to garner eventual combined annual sales of up to $50 billion.

Wednesday, September 11, 2013

Investment Commentary; Sofosbuvir- Gilead's Lurking Hepatitis C Megablockbuster Drug

Investment Commentary

In this video, health care analysts David Williamson and Max Macaluso drill down on Gilead's strong drug development pipeline.

Source - A site for investors: Motley Fool

Tuesday, September 10, 2013

Boehringer Ingelheim broadens efforts for interferon-free hepatitis C treatments through clinical collaboration with Presidio Pharmaceuticals

Related: Boehringer Ingelheim HCV Drug Development Program

10 September 2013

Boehringer Ingelheim broadens efforts for interferon-free hepatitis C treatments through clinical collaboration with Presidio Pharmaceuticals

• First Phase IIa study includes Presidio’s PPI-668 in genotype-1a infected patients1; collaboration offers the potential to explore additional HCV genotypes in future trials
• Boehringer Ingelheim’s Phase III interferon-free HCVerso® trials in genotype-1b infected patients are fully enrolled; results are expected in Q2 20142,3

For media outside USA, UK and Canada only

INGELHEIM, 10 September 2013 – Boehringer Ingelheim today announced the completion of patient enrolment for a Phase IIa clinical trial investigating a new interferon-free, all-oral, direct-acting antiviral (DAA) combination treatment for patients with genotype-1a chronic hepatitis C virus (HCV) infection. The trial is conducted in collaboration with Presidio Pharmaceuticals, Inc. and evaluates Boehringer Ingelheim’s investigational compounds, the protease inhibitor faldaprevir+ and non-nucleoside NS5B polymerase inhibitor, deleobuvir+, in combination with Presidio’s pan-genotypic NS5A inhibitor, PPI-668, with and without ribavirin.1

The trial includes 36 treatment-naïve genotype-1a infected patients treated for 12 weeks with this all-oral DAA regimen, with 24 weeks of post-treatment follow-up. The primary endpoint of the trial is sustained virologic response 12 weeks after treatment is completed (SVR12).1 This Phase IIa trial of a novel combination therapy is part of Boehringer Ingelheim’s commitment to develop new, tailored interferon and potentially ribavirin-free HCV regimens for a broad range of HCV patients.

In March 2013, the two companies entered a non-exclusive collaboration to evaluate the three DAAs in combination regimens. Both companies will retain all rights to their respective compounds. Presidio has operational responsibility for this collaborative trial, with oversight by an intercompany project team. Final results are expected in Q2 2014.1

Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim

"We are pleased to announce that enrolment is complete in this collaborative Phase IIa trial evaluating a new 12-week interferon-free treatment regimen. This regimen complements and expands our HCV portfolio with the goal of providing interferon-free treatments to patients with HCV," said Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim. "This study is the next step in our continued commitment to deliver effective and well-tolerated treatment options that are optimised for patients with different hepatitis C genotypes. The pan-genotypic properties of PPI-668 bear the potential to explore the efficacy of this regimen in a wider range of HCV genotypes in the future."

Eliminating injectable interferon from treatment is a critical goal in hepatitis C management.4 Clinical studies have shown that up to 50 percent of patients may not be eligible for treatment with interferon due to contraindications.5 Patients may also find interferon challenging due to the long treatment duration and side-effects. These side-effects commonly include fatigue, anxiety, depression, gastrointestinal and flu-like symptoms as well as more serious side-effects such as heart failure, sepsis, leukopenia, depression and vision loss.6,7

"Clinical trials evaluating multiple DAAs are exciting because they can help bring us closer to our goal of developing more effective and tolerable interferon-free and potentially ribavirin-free therapies," said Jacob Lalezari M.D., Director of Quest Clinical Research in San Francisco, CA. "By treating patients with multiple compounds that attack the hepatitis C virus in different ways, we hope to be able to cure more patients in less time with fewer of the side-effects associated with existing treatment options."

Boehringer Ingelheim has a comprehensive interferon-free clinical trial programme which includes three pivotal Phase III studies (HCVerso®). The HCVerso® studies include approximately 1,100 treatment-naïve HCV genotype-1b patients, including those who are interferon eligible or ineligible and patients with compensated liver cirrhosis.2,3

For more information regarding the trial, please visit

1. Study of PPI-668, BI 207127 and Faldaprevir, With and Without Ribavirin, in the Treatment of Chronic Hepatitis C
2. IFN-free Combination Therapy in HCV-infected Patients Treatment-naive:HCVerso1. [Last accessed 17/04/13]
3. Phase 3 Study of BI 207127 in Combination With Faldaprevir and Ribavirin for Treatment of Patients With Hepatitis C Infection, Including Patients Who Are Not Eligible to Receive Peginterferon: HCVerso2. [Last accessed 17/04/13]
4. Jazwinski and Muir. Direct-Acting Antiviral Medications for Chronic Hepatitis C Virus Infection. October 2012.
5. Kramer JR. et al. Gaps In The Achievement Of Effectiveness Of HCV Treatment In National VA Practice. J Hepatology 2012; 56:320-5
6. National Institutes of Health; US Department of Health and Human Services. Chronic Hepatitis C: Current Disease Management. Bethesda, MD: National Institutes of Health; 2010. NIH Publication 10-4230 4
7. World Health Organization. Global Alert and Response: Hepatitis C Prevention and Treatment.
8. World Health Organisation. Hepatitis C. 2002 [Last accessed on 23/07/13]
9. Centers for Disease Control and Prevention (2012) Hepatitis C available at: HYPERLINK "" [Last accessed on 23/07/13]
10. World Health Organisation. Hepatitis C Fact Sheet. Updated July 2012 [Last accessed on 16/07/13]
11. Chen S.L., Morgan T.R. The Natural History of Hepatitis C Virus (HCV) Infection. Int J Med Sci 2006; 3:47-52. Available from [Last accessed on 16/07/13]
12. Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009
13. Efficacy and Safety of BI 201335 in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-naïve Genotype 1 Hepatitis C Infected Patients. [Last accessed 17/04/13]
14. BI 201335 Used in Treatment Naive Patients Infected With Genotype 1 Chronic Hepatitis C Infection. [Last accessed 17/04/13]
15. Pivotal Trial Treatment Experienced Patient Infected With Hepatitis C Virus (HCV) Genotype 1 (GT1). [Last accessed 17/04/13]
16. Phase III Trial of BI 201335 in Treatment Naive (TN) and Relapser Hepatitis C Virus (HCV)- Human Immunodeficiency Virus (HIV) Coinfected Patients. [Last accessed 17/04/13]
17. Lalezari, J. Et al. PPI-668, A Potent New Pan-Genotypic HCV NS5A Inhibitor: Phase 1 Efficacy and Safety. Poster Presented at 63rd Annual Mtg. of the American Association for the Study of Liver Diseases. November 2012

Friday, September 6, 2013

Sofosbuvir: Firms Spar Over Hepatitis Drug

Volume 91 Issue 36 | p. 16 | News of The Week
Issue Date: September 9, 2013 | Web Date: September 5, 2013

Source - Chemical and Engineering News

Firms Spar Over Hepatitis Drug

Patents: Merck & Co., too, claims a stake in hepatitis C drug from Gilead

By Lisa M. Jarvis

As Gilead prepares for the launch of sofosbuvir, a small-molecule hepatitis C treatment that is expected to rake in billions of dollars annually, competitors are angling for a piece of the action. The latest firm to come forward is Merck & Co., which alleges that sofosbuvir’s structure is covered by patents generated in its search for hepatitis C treatments.

According to the Centers for Disease Control & Prevention, roughly 3.2 million Americans are infected with the hepatitis C virus (HCV). Battling it traditionally required a harsh, nearly yearlong regimen involving daily doses of the antiviral medication ribavirin and weekly injections of interferon. In 2011, Merck and Vertex Pharmaceuticals both launched second-generation antivirals that, when added to the combination therapy, significantly shorten treatment time.
Sofosbuvir, which came to Gilead through its 2012 acquisition of Pharmasset, would be part of the first all-oral treatment for HCV. With the Food & Drug Administration likely to approve using the drug with ribavirin before the end of the year, analysts believe Gilead could see more than $2 billion in sales in 2014 and even more in the years ahead.
“If our projections for peak sales are accurate (over $10 billion), we are not surprised that many companies have pursued complaints against Gilead to either prevent launch or receive royalties,” Deutsche Bank stock analyst Robyn Karnauskas said in a note to investors.
In a letter dated Aug. 5, Merck notified Gilead that it would grant the firm a license to two patents related to sofosbuvir in exchange for a 10% royalty on sales of the drug. Merck asked for a reply by Aug. 31; Gilead filed a preemptive lawsuit on Aug. 30.
The Merck suit comes as litigation between Gilead and Idenix Pharmaceuticals winds through the courts. Merck and Idenix both claim that sofosbuvir is covered by their patents for families of nucleoside derivatives that block RNA viral polymerase.
Analysts think Merck and Idenix are unlikely to prevail. Sofosbuvir’s activity is due to a 2'-methyl, 2'-fluoro substitution on the sugar piece of the nucleoside, a specific feature that does not seem to be in either company’s patents, says Howard Liang of investment firm Leerink Swann. Indeed, Idenix lost the latest round of its legal fight against Gilead.
Chemical & Engineering News
ISSN 0009-2347
Copyright © 2013 American Chemical Society

Saturday, August 31, 2013

Merck demand triggers expanding patent war with Gilead over sofosbuvir

UPDATED: Merck demand triggers expanding patent war with Gilead over sofosbuvir

August 31, 2013 | By John Carroll

Gilead is rolling out its big legal guns to defend its control of the experimental hepatitis C drug sofosbuvir, one of the most valuable therapies in the industry's late-stage pipeline.

On Friday the company fired over Merck's bow, filing suit in the Northern District of California after Merck contacted the company a few weeks ago to stake a claim to 10% of the revenue generated by sofosbuvir. Merck ($MRK) wants Gilead ($GILD) to sublicense two of its hep C-related patents, according to the lawsuit. The pharma giant sells Victrelis (boceprevir), its recently approved hep C drug, which is likely to be swept away as sofosbuvir and companion therapies make it to the market, offering a treatment less likely to trigger side effects and quicker to quell the virus.

In a letter filed with the lawsuit, Merck's Pamela Demain, the executive director of corporate licensing, explained on Aug. 5 that Merck was seeking the 10% royalty based on the two patents: '499 and '712. And she set an August 31 deadline for a response, drawing a line in the legal sand.

Merck's terms: "Gilead shall pay Merck a 10% royalty on the Net Sales of Licensed Product … by Gilead, its distributors or sublicensees, including sales of Licensed Product that is co-packaged with one or more other pharmaceutical products, from the first sale of sofosbuvir until the expiration of the last to expire patent within the Licensed Patent Rights."

And that's just one of several legal fights brewing as an FDA marketing decision on sofosbuvir looms in early December.

In its first-half financial report, Gilead also notes that Roche is claiming control of sofosbuvir based on a 9-year-old, $168 million partnership it struck with Pharmasset, which Gilead bought for a whopping $11 billion in order to seize full ownership of sofosbuvir while it was still in midstage development. According to the SEC filing, Roche ($RHHBY) believes that its 2004 deal to develop a nucleoside polymerase treatment with Pharmasset gives it an exclusive license on sofosbuvir, which Roche claims is a "prodrug (or precursor) of PSI-6130."

Gilead says the arbitration demand filed by Roche is without merit, noting that the deal ended about two years after it began--long before it acquired the company.

The Roche move follows an effort by Idenix ($IDIX) in 2012 to establish that it was the first to invent sofosbuvir. "Our patent covers metabolites of sofosbuvir and RG7128. Idenix is attempting to claim a class of compounds, including these metabolites, in its pending patent application," notes Gilead.

The growing flank attack on the sofosbuvir patent highlights the increasingly complex relationships among pharma companies as they become more likely to partner with academics and biotechs to broaden their pipelines. Big Phase III programs often attract litigation, like Medivation's ($MDVN) claim on Aragon's cancer therapy, ARN-509, since acquired by J&J ($JNJ). And sometimes they win, as we saw when Onyx ($ONXX) successfully laid claim to a 20% royalty of Stivarga from Bayer after bristling over its similarities to their partnered drug Nexavar.

Gilead will spare no expense in this fight. Analysts believe that sofosbuvir is an almost certain blockbuster, with peak sales estimates hovering around $4 billion to $5 billion. It's the leader in a pack of programs which are in the process of rewriting the standard of care for hepatitis C as AbbVie ($ABBV), Bristol-Myers Squibb ($BMY), J&J and other rivals hustle to catch up. And the prospect of gaining even a slice of that action is worth a considerable sum in legal costs to any company that thinks it has an actionable claim.

A spokesperson for Merck told FierceBiotech Saturday that the company has "nothing to add at this time."

Related Articles:
Gilead's sofosbuvir cures some of the toughest hepatitis C cases
Shunned Gilead/Bristol-Myers hep C combo may be too good for docs to ignore
Gilead races to FDA after hep C blockbuster hopeful scores 4th win in PhIII

Read more: UPDATED: Merck demand triggers expanding patent war with Gilead over sofosbuvir - FierceBiotech
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Gilead Sues Merck Saying New Drug Won’t Infringe Patents

Gilead Sciences Inc. (GILD), the world’s largest maker of HIV medicines, sued Merck & Co. (MRK) seeking a court order that the experimental hepatitis C drug sofosbuvir won’t infringe patents.

Merck, which sold $502 million of its Victrelis hepatitis C drug last year, contacted Gilead this month requesting it license two patents Merck says are related to sofosbuvir, Gilead’s attorneys said a complaint filed today in federal court in San Francisco.

Merck, based in Whitehouse Station, New Jersey, asked Gilead to pay a 10 percent royalty on the net sales of the medicine until the patents expire, a request “meant to threaten Gilead” on the eve of U.S. regulatory approval of sofosbuvir, according to the complaint. Gilead seeks a judge’s declarations that the patents aren’t enforceable or infringed so it won’t have to license them to sell the medicine.

Gilead, based in Foster City California, said June 7 that sofosbuvir will receive a priority marketing review by U.S. regulators with a target review date of Dec. 8.

Hepatitis C attacks the liver and can lead to liver cancer. The virus affects about 150 million people worldwide and the market for new pills such as sofosbuvir is estimated at $20 billion.

Lainie Keller, a Merck spokeswoman, didn’t immediately respond to an e-mail after regular business hours seeking comment on the lawsuit.

The case is Gilead Sciences v. Merck, 13-04057, U.S. District Court, Northern District of California (San Francisco).

To contact the reporter on this story: Karen Gullo in San Francisco at

To contact the editor responsible for this story: Michael Hytha at

Thursday, August 8, 2013

Gilead Sciences Carving Out a Wider Moat

Investment Commentary

Gilead Sciences Carving Out a Wider Moat

Stock Investor editor Matt Coffina and senior biotech analyst Karen Andersen discuss Gilead's growing competitive advantages.

By Matthew Coffina, CFA | 08-08-13 | 06:00 AM

I recently sat down with senior biotechnology analyst Karen Andersen to discuss  Gilead Sciences (GILD). A few weeks ago, we raised our fair value estimate for Gilead to $71 per share, based on positive clinical trial results and a lower cost of equity assumption. While Gilead has only a narrow moat, the moat trend is positive. If all goes well with its drug pipeline, Gilead could cross the threshold into wide-moat territory soon

Matt Coffina, editor of Morningstar StockInvestor: Gilead’s historical strength has been in HIV drugs. How has the company's portfolio of HIV drugs evolved, and where are we now in terms of growth potential and patent protection?

Karen Andersen, senior biotechnology analyst: Gilead started out with Viread, which has become the foundation of all of its marketed combination therapies. First, Gilead introduced a combination therapy, Truvada, that can be paired with treatments from other companies. Then Gilead partnered with other firms--  Bristol-Myers Squibb (BMY) and  Johnson & Johnson (JNJ)--to create single-tablet regimens Atripla and Complera. Each new drug has improved upon its predecessors. Atripla is a combination of Truvada and Bristol's Sustiva, but Sustiva causes psychiatric symptoms (depression, nervousness), rash, and elevated cholesterol, and can't be taken by pregnant women. Complera improves upon some of the neurological side effects.

Most recently, Gilead brought Stribild to market, which contains all-Gilead ingredients. Stribild combines Truvada with Gilead's integrase inhibitor, so it's like a more convenient version of Truvada plus  Merck's  (MRK) Isentress. Stribild, in my opinion, looks like a stronger regimen than Complera--it has fewer side effects than Atripla, but it might also be slightly more effective than Atripla, particularly among healthier patients. The better Stribild does, the better for Gilead, since the company doesn't have to share as much of its profit with partners and the Stribild patents go out to 2029.

Overall, Gilead now sees almost $8 billion in annual HIV drug sales. I think Gilead should continue to see high-single-digit sales growth from its HIV portfolio through 2017. These sales should flatten with the expiration of Viread patents in 2018 and begin a slow decline in 2022 as Atripla patents expire.

Matt: Everyone is excited about a variety of hepatitis C drugs in late-stage development. What is hepatitis C and how do you size the potential opportunity?

Karen: Hepatitis C is a viral infection of the liver. Patients left untreated over a period of decades usually develop chronic liver disease, such as cirrhosis, or in the most serious cases liver failure or liver cancer. Most patients in the U.S. today are baby boomers. New infection rates are quite low due to effective blood screening, so we think the market will plateau and then begin to decline as baby boomers age. However, in the meantime, the potential is enormous--there are more than 12 million patients with chronic hepatitis C in major developed markets and more than 3 million in the U.S. alone. Even if diagnosis and treatment rates only improve incrementally over the next few years, we think the global annual market will hit $20 billion by the end of our 10-year forecast.

Matt: Recent clinical trial data for Gilead’s hepatitis C drugs has been very promising. Can you summarize the efficacy and side-effect profile?

Karen: Gilead's strategy is to bring the foundation of its hepatitis C portfolio, sofosbuvir, to market in 2014, and a combination with another drug candidate, ledipasvir, to market in 2015. This oral combination therapy is particularly promising, and efficacy in a recent Phase II trial indicated that cure rates could be as high as 100% after 12 weeks of therapy, with few side effects. For perspective, the current standard of care (with drugs like  Vertex Pharmaceuticals(VRTX) Incivek) results in cure rates of around 70% for most previously untreated patients, treatment typically lasts for six months, and side effects--including flulike symptoms, depression, and anemia--prevent many patients from finishing or even initiating therapy. In addition, current treatment involves a complex regimen of once-weekly injections and around a dozen pills a day, while Gilead's regimen will be a once-daily pill.

Matt: How do Gilead’s drugs compare to those in development at competitors like  AbbVie (ABBV), Bristol, Johnson & Johnson, and Vertex?

Karen: Given the market potential I outlined, it is no surprise that several other firms are vying to enter this market. AbbVie is likely to bring its own all-oral combination regimen to market in 2015, but we expect this regimen to require ribavirin, which is part of the current standard of care but which causes anemia. It will also require several pills per day in order to achieve efficacy on par with Gilead's combination regimen. Bristol may be able to bring a ribavirin-free regimen to market with similar efficacy to Gilead's, but Bristol is just entering Phase III trials and also requires several pills per day. I'm most concerned about competition from Vertex, which has a drug that could be similar to Gilead's sofosbuvir. However, Vertex's key trials are only at the Phase II level, which will make the product late to market. Unless Gilead's regimen sees surprisingly weak efficacy in Phase III trials or Vertex is able to significantly shorten treatment times (Gilead is already testing its regimen as an eight-week treatment), we doubt it will be able to offer any improvements relative to Gilead's product.

Matt: Gilead built out its hepatitis C portfolio through the $11 billion acquisition of Pharmasset. Do you think the price it paid was low, high, or about right, given what we know now?

Karen: Given the data we have seen for sofosbuvir and competing products over the past year, we have gone from estimating Pharmasset was purchased at a fair price to estimating it was actually a bargain. For example, last year we conducted a net present value analysis of the acquisition, which implied that Gilead had paid a fair price for Pharmasset assuming a discount rate of 10.2% and $4.5 billion in annual sofosbuvir sales by 2020, followed by flat sales through patent expiration. Today, we assume less than an 8% cost of capital and sales of sofosbuvir flattening around $8 billion by 2020, and the acquisition now looks like it was worth at least twice what Gilead paid.

Matt: Gilead seems to have special expertise in infectious diseases and single-pill formulations that carry across drug classes. Would you agree, and what might this mean for future innovations?

Karen: I think we're starting to see that play out, as the firm's ability to recognize valuable molecules in HIV and strategically create the best combination regimens is clearly carrying over to the field of hepatitis C. I think this is one of the reasons why Gilead will be able to hang on to the high market share it will undoubtedly gain after the launch of sofosbuvir, despite emerging competition. Gilead has a large pipeline of hepatitis C drug candidates that could allow it to serve a broader group of patients with an even shorter duration of therapy. Gilead is also beginning to advance in the field of oncology, which might sound like a stretch. However, Gilead is focusing initially on hematological oncology, where progress looks like it will be heavily focused on combination regimens in niche markets, which is Gilead's specialty.

Matt: We assign Gilead only a narrow economic moat, but the moat trend is positive. What would it take for the company to cross the threshold into wide-moat territory, in your view?

Karen: Assuming clinical data continue to support our thesis that Gilead's hepatitis C pipeline is clearly superior to those of its key competitors, we expect to assign the firm a wide economic moat once sofosbuvir reaches the market (by early 2014). We think patent protection on newer HIV regimens as well as Gilead's lead in producing an all-oral hepatitis C cure will be enough to ensure strong returns for the next couple of decades, and we think visibility on profits is clearer at Gilead than at many of its large-cap biotech peers.

Final thought from Matt: Biotechnology can be a risky place to invest, full of high hopes and dashed dreams, where luck is often as important as skill in the hit-or-miss game of drug development. However, a small handful of biotechs have managed to carve out wide economic moats, based on patents, scale, and the ability to leverage unique expertise across a diversified portfolio of drugs. Gilead appears to be headed in this direction.

Tuesday, July 23, 2013

Plenty Of Room For Everyone In The Race To FDA Approval For New Hepatitis C Therapies

Investment Commentary

Plenty Of Room For Everyone In The Race To FDA Approval For New Hepatitis C Therapies 

Jul 23 2013, 12:32
Seeking Alpha
By Visit Three Knights Capital, Inc.

The United States Preventive Services Task Force, or USPSTF, reversed its stance late on June 25 to conclude that all baby boomers - those people born between 1945 and 1965 - should be tested for hepatitis C. The USPSTF is an influential medical guidelines organization that advises Congress and, as its website reads, "makes recommendations about the effectiveness of specific preventive care services for patients without related signs or symptoms."

The recommendation of the USPSTF could lead to health insurance companies having to pay for screening under the revamped U.S. healthcare laws that start next year. It also could also lead to a lot more diagnoses of hepatitis C infections and a boon in sales for pharmaceutical companies. According to the Centers for Disease Control and Prevention, about 3.2 million Americans have the chronic version of the hepatitis C virus (HCV). Worldwide, it's estimated that more than 150 million people are infected with HCV, according to the World Health Organization.

HCV is a viral infection that can lead to swelling of the liver, cirrhosis, the need for transplant, and possibly even liver cancer. Today's standard of care is the injectable interferon, which is well documented to cause flu-like side effects. Because of the side effects and the method of delivery, new therapies that treat HCV more quickly are in great demand. Demand and potentially changing guidelines have planted several companies firmly on investors' radar.

A definite leader in the treatment of HCV is Gilead Sciences, Inc. (NASDAQ: GILD), with shares rising about 45 percent in 2013 as optimism for its oral HCV medication, sofosbuvir, are soaring. The drug is meant for use in combination with pegylated interferon and/or ribavirin, and represents what most consider the next generation of HPV therapies as an all-oral regime. Gilead's interferon-free ELECTRON trial of sofosbuvir demonstrated a strong response rate in patients with HCV genotypes 2 and 3 treated only with sofosbuvir and ribavirin.

Gilead, the world's biggest maker of HIV drugs, diversified into the HCV market by snagging the promising drug - and two other HCV drug candidates - in its $11.1-billion acquisition of Pharmasset, Inc. in November 2011. On June 10, the U.S. Food and Drug Administration granted Gilead priority review, following completion of Phase III clinical trials for the drug. Gilead is hoping for approval no later than early in December this year. S&P Capital IQ maintains a 5-STAR "Strong Buy" recommendation for Gilead.

Gilead may be leading the pack, but it is not alone in a race that will likely deliver billions of dollars in sales to the first to market. AbbVie (NYSE: ABBV) is nipping at Gilead's heels with its own all-oral, interferon-free treatment for HCV, with and without ribavirin. Much like sofosbuvir, AbbVie's HCV protease inhibitor ABT-450, in combination with other AbbVie drugs, produced strong response rates of greater than 90 percent in only a few months. ABT-450 was developed in a joint effort with Enanta Pharmaceuticals, Inc. (NASDAQ: ENTA).

AbbVie's drugs, ABT-450/r, ABT-267 and ABT-333, have received the vaunted "Breakthrough Therapy" designation from the FDA. A "Breakthrough Therapy" designation from the FDA, a relatively new category from the FDA (initiated in 2012), is meant to expedite the regulatory process for drug candidates that may meet great areas of unmet medical need. To date, the FDA has received over 60 applications for "Breakthrough Therapy" designation, but only 15 have been awarded, with AbbVie commanding three of them with its HCV treatments.

Shares of ABBV have also lofted higher, rising about 27 percent in 2013, on bets that they can catch Gilead in the quest for FDA approval to market a new HCV treatment. The Breakthrough designation gives AbbVie an outside shot, but Gilead appears to still be out front in a very close contest.

Even if one or both win the thumbs-up from the FDA, there are a host of other companies running the regulatory gamut with HCV drugs that can certainly still benefit in the future. It's also notable that both AbbVie's and Gilead's treatments would likely include ribavirin, a drug that many patients have difficulty tolerating. Bristol-Myers Squibb (NYSE: BMY), developing a ribavirin- and interferon-free treatment, is certainly in the hunt. BMS already has Baraclude approved for the treatment of chronic hepatitis B and several ongoing clinical trials testing its antiviral cocktails. In May, the company completed a Phase III trial of BMS-790052 and BMS-650032 in Japanese HCV patients. Japan has recently unveiled plans under Prime Minister Shinzo Abe that are meant to raise the number of clinical applications by consolidating management of research money. To that end, it will be interesting to see where BMS goes with this research moving forward.

Shares of BMY have risen about 23 percent so far in 2013.

Johnson & Johnson's (NYSE: JNJ) oral HCV drug, simeprevir, received priority review from the FDA in May and has also delivered very promising clinical data. It's noteworthy that research has been conducted combining simeprevir with Gilead's sofosbuvir with compelling results. That's another point in recognizing that there can be more than one blockbuster drug in the massive HCV industry. Several of the drugs in development could eventually receive FDA approval and potentially be used together to treat patients.

Shares of JNJ are up about 29 percent in 2013.
Read Full Article : Plenty Of Room For Everyone In The Race To FDA Approval For New Hepatitis C Therapies

Tuesday, June 25, 2013

Top Medicare Prescribers Rake In Speaking Fees From Drugmakers

Top Medicare Prescribers Rake In Speaking Fees From Drugmakers

by Charles Ornstein, Tracy Weber and Jennifer LaFleur
ProPublica, June 25, 2013, 12:02 a.m.

This story was co-published with NPR

When the blood pressure drug Bystolic hit the market in 2008, it faced a crowded field of cheap generics. 
So its maker, Forest Laboratories, launched a promotional assault on the group in the best position to determine Bystolic's success: those in control of prescription pads. It flooded the offices of health professionals with drug reps, and it hired doctors to persuade their peers to choose Bystolic — even though the drug hadn't proved more effective than competitors. 
The strategy worked. In the 2012 fiscal year, sales of Bystolic reached $348 million, almost double its total from two years earlier, the company reported. 
Now, data obtained and analyzed by ProPublica suggest another factor in Bystolic's rapid success: Many of the drug's top prescribers have financial ties to Forest. 
At least 17 of the top 20 Bystolic prescribers in Medicare's prescription drug program [2] in 2010 have been paid by Forest to deliver promotional talks. In 2012, they together received $283,450 for speeches and more than $20,000 in meals............ 

Full article available here.........

Wednesday, June 12, 2013

Inside HCV: An Interview with Janssen

Brandy is a member of The Motley Fool Blog Network -- entries represent the personal opinion of the blogger and are not formally edited.
Our job here is to examine companies through an investing perspective. But in churning out numbers and comparing potential product sales, we sometimes overlook the human element. Right now, the Food and Drug Administration is on the cusp of approving two hepatitis C drugs that could revolutionize patient cure rates.

I recently discussed simeprevir, the promising HCV candidate from Johnson & Johnson (NYSE: JNJ) subsidiary Janssen. The drug achieved impressive cure rates in mid-stage trials when paired with Gilead’s (NASDAQ: GILD) sofosbuvir. Simeprevir remains in mid-stage trials with a variety of partners including Vertex (NASDAQ: VRTX).

I spoke last Friday with Dr. Gaston Picchio, Hepatitis Disease Area Leader for Janssen, about the company’s willingness to collaborate -- and how now is the best time in history to be a hepatitis C patient.

Collaboration prospects

Brandy Betz: The priority review news was fantastic, but analysts are watching for the interferon-free results. Would you please discuss the all-oral trials involving simeprevir and Janssen’s willingness to form partnerships for the best combo therapy?

Dr. Picchio:  We are absolutely committed to partnerships.

Some people believe that there are companies that have all of the necessary ingredients to come up with these interferon-free regimens. And the companies basically say, “We have all of the components. We feel very confident with what we have and we’re going on our own.”

We have internal components -- but we’re also looking at external components. I think a reflection of that is the fact that we have four ongoing collaborations today. We have one with Gilead. We have one with Idenix. We have one with Bristol-Myers Squibb. And we have one with Vertex.

We’re at the stage where we’re exploring simeprevir’s potential. Simeprevir has so far reported data in combination with sofosbuvir, and the results are extremely promising. If I were a null responder patient -- the toughest to cure patients -- I would see that simeprevir plus sofosbuvir for 12 weeks resulted in a 93% cure rate. And I would be very excited, because this is what’s coming.

So we continue to explore with other companies, and with our internal assets, for what is the best possible combination for the safest possible regimen, the shortest possible regimen and the most efficacious one. But we’re in a stage where we’re generating data. So I cannot say what will be the best possible collaborations that we could pursue.

Commercialization prospects

GP: There’s an important part to clarify. I’m always asked about commercial agreements and I want to be very clear that, at this point in time, we don’t have any commercial agreements in the partnerships I just described. We have clinical collaborations to understand simpeprevir’s safety and efficacy in combination with all of these drugs.

BB: It's hard to answer commercialization questions when you're in mid-stage trials. 

GP: People want more definitions about commercial things, and those are equally important. I’ll give you an interesting example.

Simeprevir and sofosbuvir are the two drugs that are right now under review. They could come to approval towards the end of next year, depending on the FDA. You hear a lot at the conferences, talking to experts. They say, “Oh, simeprevir and sofosbuvir are going to be approved with the use of ribavirin and interferon. Why not take these two drugs and combine them?”

So that’s just the beginning of the era of being interferon-free. As you know, companies like Gilead or AbbVie or Janssen come with regimens already formulated and things like that. But this may be the beginning of that era.

The most important thing happening is that this is going to benefit patients so much that I don’t think we understand the dimensions of that.

BB: This is one of the most important times in recent medical history. These new treatments, particularly for patients with genotype 1, are going to open up a whole new world.

GP: Absolutely. Imagine a world where there are no financial restrictions and you say, “I want to give treatment to everyone.” Even if you want to do that, you can’t --  because the vast majority of patients can’t tolerate or have contraindications with interferon-ribavirin.

But if we have interferon-free treatments, the story’s completely different. Because we can deliver a very simple regimen over a relatively short period of time -- perhaps 12 weeks or less -- and that’s when it’s gong to get very interesting. And these new regimens appear more efficacious. But we have to be careful there because we don’t have a lot of data.

But you look at our studies, you look at other people’s studies. Talking about null responders ... some people with cirrhosis who’re getting cured at a very high rate. It looks very good for patients. It’s probably the best time ever to have hepatitis C. There are very promising treatments coming along.

BB: I’ve spoken to hepatitis C patients in the past couple of weeks as I’ve increased my coverage, and there's universal excitement about what's coming down the pipes. 

GP: I think it is the fastest-moving field in the history of medicine. I cannot think of anything else. I was just talking to people with expertise in other areas, trying to understand it. They’ve never seen such a fast evolution over such a short period of time.

Before 2010,  it was taking 48 weeks to cure 40% of the patients. And now we’re talking about 8 weeks with cure rates of 95% with minimal side effects. It’s amazing.

Is bigger really better?
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Friday, May 31, 2013

Commentary: Gilead's agent is the holy grail of HCV treatment

Source - About Medical Marketing & Media

Therapetic Focus: Infectious Diseases
Therapeutic: Infectious (download) 

For those awaiting changes in the treatment of hepatitis C, it's almost time to toss the confetti. The field is on the verge of one of the most profound upgrades in any therapeutic category, promising real progress in efficacy, tolerability and convenience. Barring any safety bombshells, a prolific pipeline of direct-acting anti-viral agents (DAAs) is due to start issuing forth options that, when combined, will permit all-oral, interferon-free treatment.

By making future HCV treatment shorter, safer, easier and more effective, says Jonathan Fenkel, MD, director of the hep. C center at Thomas Jefferson University, these protocols “will open the door to many more patients who have declined or deferred treatment.”

That could mean billions in sales. Analysts say new therapies could help grow the pie for the virus to $20 billion annually by 2020. The infectious diseases market, as a whole, rose from $33.6 billion in 2011, to $35.2 billion in 2012, according to data compiled by IMS Health on sales of hep. C and HIV drugs, as well as antibiotics and vaccines.

Clinicians and analysts agree that the first and likely go-to therapy will eventually be Gilead Sciences' sofosbuvir (GS-7977). Gilead has applied for approval of sofosbuvir and ribavirin as an all-oral therapy for patients with genotypes 2 and 3—the minority of patients with hep. C in the US (about 75% of patients are genotype 1).

Gilead's agent is the “holy grail of HCV treatment,” analyst Julie Hoggatt tells MM&M. The first hep. C drug to cut treatment duration to 12 weeks, vs. 24 weeks with the available DAAs (Vertex's Incivek or Merck's Victrelis), it boosts efficacy from a 70% cure rate to over 80%. Phase II data from Gilead suggest a further 33% reduction in treatment duration—from 12 weeks down to eight—in patients taking a combination of sofosbuvir and Gilead's ledipasvir, aka GS-5885.

The nucleotide analogue polymerase inhibitor (or “nuc”) has broad-spectrum genomic activity (meaning that it covers multiple hep. C genotypes), a barrier to the development of viral resistance, has once-daily dosing, and can be co-formulated with other agents.

Other players include AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Merck, Vertex and smaller biotechs. Some could find a niche among the difficult-to-treat population. But, says Hoggatt, a principal with Symphony Health Solutions' inThought Research, “We are forecasting Gilead to be the clear majority player, with sofosbuvir capturing 75% peak market share.” She predicts approval as early as mid-December for use in genotypes 2 and 3. By 2015, sofosbuvir's label is likely to be expanded as part of an all-oral regimen for the more common genotype 1, when combined with ledipasvir.

In the meantime, in Thought expects some off-label use of sofosbuvir plus ribavirin without interferon in treatment-naïve genotype 1 patients, the analyst wrote in an April research note in which she modeled peak worldwide sales of $4.3 billion for sofosbuvir. This is a conservative forecast, below street consensus which is over $7 billion.

“Shortening treatment and lowering the pill burden will have a huge effect on compliance, efficacy, and acceptance,” says Jefferson's Fenkel. Not to mention safety: IMS analyst Steve Gubernick notes, “You don't have to worry about paying for side effects anymore.”

This is a wholesale transformation from today's standard of care, which incorporates pegylated interferon (PEG-IFN), ribavirin and a protease inhibitor (Incivek or Victrelis). Many of today's HCV treaters are holding patients back until the new wave of oral medication hits.

According to Hoggatt and others, the next most-dominant company in the HCV market after Gilead will likely be AbbVie, whose multi-drug oral regimen has high efficacy among null responders. It scored FDA's “breakthrough” status, as did BMS hep. C drug daclatasvir.

In testing, daclatasvir with asunaprevir and BMS-791325, produced a high cure rate in prior treatment failures. And BI presented data on NS3/4a protease inhibitor faldaprevir which, in conjunction with pegylated interferon and RBV, had a 79-80% rate of cure in a group that had a high proportion of tough-to-treat cirrhotic patients.

Hep. C is, for most patients, not fast-moving, so they can wait for new options. In a research note, ISI Group analyst Mark Schoenebaum, MD, estimated that around 350,000 US patients are under the care of a hep. C specialist and can be easily accessed and activated once new treatments arrive. The challenge is getting patients diagnosed and into the medical system; and, once they are, managing the potential flood of treatment-eligible patients. There are about three million infected patients in the US, four million in Western Europe, about a million in Japan and seven million in Eastern Europe.

Another caveat: Who'll pay for the new regimens, which could cost $100,000 or more for a three-month course. While today's regimens cost from $65,000-$80,000, according to ISI's Schoenebaum, “I [w]ould be very surprised if [sofosbuvir] were priced significantly less than $80k, and wouldn't be shocked to see $100k.” inThought's Hoggatt models a wholesale cost closer to $54,000 for a 12-week course.

What is dictated by the payers will be important. “If we have equal efficacy and side-effect profiles for all of the regimens, the payers may have preferences,” says Paul Pockros, MD, division head of gastroenterology and hepatology at the Scripps Clinic in San Diego. Of course, all of this new drug excitement is unfolding against the backdrop of ObamaCare, rolling out in 2014. That means more people covered, but leaves guesswork as to the span of pharmaceutical coverage.

While a revolution is under way in hep. C, in HIV/AIDS it's more of an evolution. With the approval of Gilead's quad-pill Stribild, there are three one-pill, once-a-day, single-tablet regimens available, all with high efficacy and favorable tolerability. Attention is focused mostly on the safest, most convenient way to treat patients chronically for life.

“Our focus is still on the safest regimens that give patients a healthy lifespan without cumulative toxicities,” says Cal Cohen, MD, a leader in HIV research and an instructor at Harvard University. Cohen spotlights two investigational anti-retroviral medications in the pipeline. Gilead's tenofovir alafenamide fumarate (TAF; GS-7340) has so far shown greater antiviral activity with potentially fewer concerns about kidney function or bone mineral density. The other investigational agent Cohen's eying is ViiV's second-generation integrase inhibitor dolutegravir, which has demonstrated sustained efficacy and once-daily dosing, without the need for a pharmacokinetic booster.


The days of interferon are numbered. So, what are the next important milestones in the evolution of hepatitis C drug development? The two next big signposts, sources say, are the removal of ribavirin from treatment protocols as well as the further truncating of HCV regimens to as short as eight weeks, down from today's 24-48.

Ribavirin is a double-edged sword. It has been shown to reduce the rate of relapse and it's cheap. But it's a weak anti-viral whose mechanism of action against HCV is not well understood, and it's dosed twice daily. RBV, as it's known, also brings such side effects as anemia, so physicians can't dose it in patients with kidney impairment, and teratogenicity (a contraindication in pregnant women).

The latter “complicates recruiting women of child-bearing age into clinical trials—a substantial number of HCV patients!” says Wayne Dankner, MD, global therapeutic area lead for infectious diseases and pediatrics with the CRO Parexel. It also affects male subjects as they must “practice adequate birth control with their female partners,” he adds.

Multiple strains of evidence from the clinical literature suggest that it may be possible to show ribavirin the door. Manufacturers like Gilead, AbbVie and Bristol-Myers Squibb are trying to identify other direct-acting anti-virals that can replace RBV in the regimen or to find agents that are sufficiently robust to obviate the need for it altogether.

The other opportunity on the horizon is to reduce the duration of therapy—an opportunity highlighted by the announcement of Gilead's Phase II Lonestar data in early May. Lonestar demonstrated a 95-100% cure rate after eight weeks of therapy with a fixed dose combination of Gilead's nuc sofosbuvir plus the NS5a ledipasvir (GS-5885).

“While most of these regimens are 12 weeks in duration, there is a continual focus on whether we can shorten to eight weeks. That would improve acceptance and lessen exposure to drugs,” says Dankner.

Another important future development is providing effective therapy to patients with more advanced liver disease, such as cirrhosis, and those with multiple co-morbidities, including HCV/HIV co-infection. Such patients have historically been much more difficult to treat.

“Enrollment of a population representative of the disease being treated is critically important,” says Peter Piliero, MD, Boehringer Ingelheim VP, clinical development and medical affairs. Other typical patient characteristics, Piliero adds, include those with both HCV genotype 1 subtypes (1a and 1b) and the various IL28b polymorphisms.

But scientists looking for new HCV treatments are not starting from scratch. Most of the companies in the field have cut their teeth developing antiretroviral agents for HIV. “We'll have a second generation of agents coming right on the heels of the first generation,” says UCSD School of Medicine's Bob Gish, MD, chief of clinical hepatology and professor of clinical medicine. “The warp speed we're seeing is because of that historical experience in other viral illnesses.”
From the June 2013 Issue of MMM

Investment Commentary Today @ Seeking Alpha

The Race For Oral HCV?

Gilead Sciences (GILD) announced on May 21, 2013 that the European regulator EMA (European Medicines Agency) started the process of assessing the company's once daily oral treatment for hepatitis C virus (HCV) and will furnish an accelerated review.

Earlier, on May 13, Johnson & Johnson's (JNJ) experimental drug, still in mid-stage trial, got priority review status from the FDA. A week earlier, the FDA accorded breakthrough status to the Hepatitis C virus regimen of AbbVie (ABBV).

The race, therefore, is on.

Continue reading at Seeking Alpha

Tuesday, April 16, 2013

Achillion -1 Biotech Challenging the Hep-C Goliath

Related Press Release - Achillion Initiates Phase 2 Interferon-Free Trial of Sovaprevir and ACH-3102 for Genotype 1 HCV

Investment Commentary

In this video, David Williamson describes how Achillion Pharmaceuticals may challenge Gilead's dominance in the Hepatitis C drug market. Achillion is concluding phase 2 clinical trials of its oral interferon medication, and so far, things are looking good. If successful in phase 3 trials, Achillion could directly challenge Gilead's interferon medication. For investors, the success of Achillion's drug is attractive, but the potential for Achillion to be a takeover target is even more enticing. The company has a market cap of around $575 million and could easily be bought out by the likes of Bristol-Myers Squibb.

Check out the video for more details.

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Wednesday, March 27, 2013

Gilead-Medivir Hepatitis C Drug Clears Virus in Patients

Gilead-Medivir Hepatitis C Drug Clears Virus in Patients

By Ryan Flinn & Shannon Pettypiece

An automated machine works on purification of a potential hepatitis C virus drug candidate at the Gilead Sciences Inc. lab in Foster City,

California. Photographer: David Paul Morris/Bloomberg

An experimental drug combination from Gilead Sciences Inc. (GILD), Medivir AB (MVIRB) and Johnson & Johnson (JNJ) eradicated the virus that causes hepatitis C in patients with the liver disease in a study.

The trial’s 80 patients, who had tried and failed other medications, took a two-drug mixture of Medivir’s simeprevir and Gilead’s sofosbuvir, according to research presented at the Conference on Retroviruses and Opportunistic Infections today in Atlanta. The patients took the combination for 12 or 24 weeks, with and without the antiviral ribavirin, researchers said.

“We went for the most difficult to cure, with the idea if we could show good efficacy there, it could be assumed the regimen could be efficacious in other patient populations,” Gaston Picchio, hepatitis disease area leader for J&J’s Janssen unit, said in a telephone interview. Medivir, based in Huddinge, Sweden, is working with J&J to develop simeprevir.

The interim results showed that among the 10 patients who had been off the treatment for 12 weeks, all of them still had their virus suppressed.

Gilead, Medivir and J&J are competing with Abbott Laboratories (ABT), Bristol-Myers Squibb Co. (BMY), Merck & Co. (MRK) and Vertex Pharmaceuticals Inc. (VRTX) to develop a new generation of oral hepatitis C treatments. The goal is to eliminate the standard therapy that requires ribavirin and an injection of interferon, an immune-boosting protein that can cause flu-like side effects for as long as 48 weeks.
Fewer Effects

Hepatitis C affects about 150 million people worldwide, according to the World Health Organization. The new drug regimens in testing are designed to be taken as pills, with shorter treatment durations and fewer side effects.

“Sofosbuvir continues to look like a backbone treatment,” said Brian Skorney, an analyst with Robert W. Baird & Co in a note to clients. “These results support our belief that sofosbuvir’s profile allows it to be combined with virtually any active HCV agent and eliminate the need for interferon and ribavirin.”

Gilead rose 1 percent to $43.87 at the close of trading in New York. The shares of the Foster City, California-based company had gained 87 percent in the past 12 months. Medivir climbed 3.8 percent to 90 kronor.

Gilead Therapy

While Gilead is unlikely to pursue a partnership with Medivir and J&J since the company is developing a combination of its own therapies, doctors may prescribe the pair reported in the study off-label, Brian Abrahams, an analyst with Wells Fargo Securities in New York, said in a note today.

“Of course, this would depend on pricing of the two components and payer acceptability, though with elimination of interferon and possibly ribavirin costs and side effects and substantial sustained virologic responses we believe the would likely be amenable,” Abrahams wrote.

Vertex is also testing an experimental drug, VX-135, with Medivir’s Simeprevir, and today’s clinical trial results could make that combination more likely, if no safety issues emerge, Abrahams said.

To contact the reporters on this story: Ryan Flinn in San Francisco at; Shannon Pettypiece in New York at

To contact the editor responsible for this story: Reg Gale at

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