HCV New Drugs: Gilead May Top Rivals With Hepatitis C Therapy Results

Investment Commentary

Fierce Biotech

Hep C pill race report 2012: Gilead, others rush toward pharma gold
November 14, 2012 | By Ryan McBride

Vertex Pharmaceuticals ($VRTX) radically improved the treatment of hepatitis C with its protease inhibitor Incivek, which fast became a blockbuster success after the FDA stamped an approval on the drug in May 2011. Investors and physicians cheered, thousands of patients embraced the treatment, and Vertex's sales skyrocketed.

Temporarily. Early this month, Cambridge, MA-based Vertex reported financial results that showed a steep decline in sales of Incivek, down from $419.6 million in the third quarter of 2011 to $254.3 million in the same period this year.

Blame much of the 39% drop in sales of the drug on at least a couple of related factors. Firstly, Incivek is approved only for use with injected interferon, which causes a range of nasty and flulike side effects. Secondly, physicians and patients appear to be waiting for a new generation of oral antivirals that offer the promise of wiping out the virus relatively quickly without requiring interferon injections.

This wasn't news to Vertex. Along with a bevy of competitors, the pharma company has hurried to advance interferon-sparing treatments for a while. If the all-oral therapies now in development hit the market as expected within the next couple of years, sales of interferon-based treatments are in big trouble. Vertex knows this. Merck ($MRK), which markets the rival hep C drug Victrelis, knows this. Both companies are hustling to develop all-oral approaches to fighting the disease.

"Obviously, we're moving as fast as we possibly can," Dr. Robert Kauffman, Vertex's chief medical officer, said in an interview with FierceBiotech. He also noted: "The news is that the field is changing rapidly; all-oral regimens look to be on the horizon."

The evolution of hepatitis C treatment threatens to leave today's dominant companies with fossilized offerings. Vertex and Merck have the state-of-the-art approved drugs against the virus, but both companies are chasing after Gilead Sciences ($GILD), Abbott Laboratories ($ABT) and others with programs that could be the first to win market approval with pill-only options.

There's no cozy position in the hep C race, however. The all-oral cocktails are largely unproven and in need of confirmation in fully baked pivotal studies, and that keeps the contest wide open for a number of contenders, Vertex included.

Oral hep C nucs: Virus assassins or toxic agents?
Bristol-Myers Squibb ($BMY) killed development of its once-promising nucleotide polymerase inhibitor in August after a patient who took the experimental compound, known as BMS-986094, died of heart failure. The death sounded the safety alerts at the FDA, which hit the brakes on studies of the "nuc" drug in August. And by the time Bristol put the kibosh on further development of the compound on Aug. 23, a total of 9 patients had been hospitalized, including the person who had died.
The "094" disaster was felt across the industry. The FDA quickly called for a hold on development of two hep C pills from Idenix Pharmaceuticals ($IDIX). The first, called IDX184, is in midstage development and was placed on partial clinical hold, and the second, IDX19368, is a preclinical compound from the same drug class. Both experimental pills share similarities with Bristol's doomed nuc.

Idenix has to prove that its clinical-stage drug isn't another toxic dud before further trials in patients can resume. Hopeful to resume testing of IDX184, Idenix made clear at the American Association for the Study of Liver Diseases annual meeting that there's been no evidence of severe heart side effects in patients on the pill.

Bristol managed to let its 094 program die while maintaining that the cause of the death and hospitalizations among patients who took the drug was uncertain. Nevertheless, toxicity concerns hang like a dark cloud over the enterprise of advancing new nucs against hepatitis C virus.

Idenix's and Bristol's woes have made news recently, but safety problems have plagued a number of previous oral compounds against the liver-damaging virus. NM-283, a nucleoside polymerase inhibitor from Idenix developed in partnership with Novartis ($NVS), fell from grace years ago after investigators found gastrointestinal side effects. Roche's ($RHHBY) polymerase inhibitor, R1626, was axed after doctors saw evidence of bone marrow suppression.

"Anytime we study a new 'nuc,' we're on alert for those kinds of side effects," said Dr. Paul Pockros, head of the division of gastroenterology/hepatology at the Scripps Clinic's Liver Disease Center, in an interview with FierceBiotech.

Pockros, who was involved in the ill-fated study of Bristol's 094, said that the death of the patient from heart failure has heightened concerns about potential cardiovascular side effects of nucs in hep C studies.

Hep C bigger than HIV
Intravenous drug use, dirty tattoo parlors, tainted blood transfusions and carriers infecting offspring are several of the many ways an estimated 170 million people around the world have contracted hepatitis C. In the U.S., estimates place the total number of cases at 4 million, making the disease far more prevalent than headline-grabbing HIV in the country.
The good news for hep C-infected patients: Current therapies offer viral cures, and others in development could wipe out the illness faster than today's drugs. The bad news: Most people with the chronic disease are unaware of their illness, according to the Centers for Disease Control and Prevention (CDC). Many of them are from the baby-boomer generation.

Hepatitis C damages liver tissue and results in scarring known as cirrhosis. Once a patient has cirrhosis, he's got a greater risk of developing liver cancer, liver failure and dying. In fact, the virus is responsible for driving up rates of liver cancer, liver transplants and liver failure.

It takes decades before the virus significantly damages the liver. With the disease killing higher numbers of aging boomers, the CDC made new guidelines this year for physicians to screen all their patients born between 1945 and 1965 for the virus. But the jury is out on how well the guidelines will be followed.

For developers of hep C drugs, the HCV testing could benefit sales of meds against the disease. Yet unless a patient's hep C has made him sick, doctors might keep him on the sidelines in anticipation of the all-oral therapies hitting the market in 2014.
"If you already have cirrhosis, and you're scared that you may be decompensated and could develop cancer, you may want to take what's available," Dr. Guadalupe Garcia-Tsao, president of the American Association for the Study of Liver Diseases, told reporters last week in Boston. Otherwise, she said, hep C patients might want to wait for next-generation therapies.

A pharma gold rush
There are plenty of arms races in the pharma industry, with companies sprinting to advance rival therapies to market. Yet few move as quickly as the hep C race, and the lucrative market and clinical development dynamics are incentives to work fast.
"If you go away for a couple hours, things change in HCV," laughed Joseph Truitt, head of business development for Achillion Pharmaceuticals ($ACHN), a developer of three clinical-stage drugs against hep C.

The hep C drug market saw explosive growth in 2011 with the introduction of Merck's ($MRK) and Vertex's ($VRTX) then newly approved protease inhibitors, which boosted sales in the category by about $1 billion last year to $2.6 billion, according to market research from GBI Research. With patients waiting for all-oral options, no such growth is in the offing for 2012.
The interferon-free cocktails could trigger tremendous growth in a few years, many say by 2015, when multiple all-oral regimens could be on the market. The market could grow to nearly $15 billion by 2018, with Gilead ($GILD) and Abbott ($ABT) controlling the largest two pieces of the pie, respectively, according to GBI. Bloomberg says $20 billion by 2020. These are irresistible numbers for many pharma outfits.

Gilead famously forked over $11 billion for Pharmasset this year, spending an enormous sum to gain its lead nuc drug, GS-7977, and arguably the leading position in the all-oral-regimen race. And if the company's late-stage studies pan out as well as hoped, the multibillion-dollar gamble will become money well spent.

Nuc or no nuc
Credit or blame Pharmasset for much of the fervor over nucs. Last year the company wowed industry watchers with midstage study data of interferon-free regimens built around GS-7977, which appears to crush the ability of hep C virus to build resistance to treatment. Then the theory went: If you want take interferon out of the hep C cocktail, you might need a nuc.

Last week Gilead ($GILD) reaffirmed why Pharmasset might be worth the fortune it paid for the precommercial outfit. Gilead unveiled impressive data during the American Association for the Study of Liver Diseases meeting (AASLD) meeting that showed there were no detectable signs of HCV four weeks after treatment in 100% of 25 genotype 1 patients who took a 12-week course of 7977; the company's NS5A pill, GS-5885; and ribavirin. These were patients who had never taken interferon-based treatments.

Bristol ($BMY), conversely, lost big on a $2.5 billion bet on Inhibitex early this year after the 094 nuc compound from the developer flamed out in Phase II and a study patient died this summer.
"094 we thought was a reasonable bet, a reasonable hedge should the science tilt toward the you-must-have-a-nuc" theory, Dr. Doug Manion, senior vice president of development for virology at BMS, said in an interview. "But since then the science has evolved that we now know from the Abbott data and our own data that a nuc isn't quite as important as everyone thought."

In October and in detailed data presented during the AASLD meeting, Abbott impressed with an all-oral combination of 5 drugs, none of which are nucs, in a Phase IIb study. Tests showed no signs of the virus 12 weeks after treatment in 97.5% of treatment-naïve patients with the most common type of hepatitis C, genotype 1, on Abbott's ($ABT) ABT-450/r (a protease inhibitor boosted with the HIV drug ritonavir), ABT-267 (a polymerase inhibitor), ABT-333 (an NS5A inhibitor) and ribavirin. Its Phase III program for the regimen is enrolling patients.

Bristol, which got into the hep C game long before it bought Inhibitex, has tested multiple all-oral combos sans nucs with upbeat results. For instance, this week the company highlighted data from a midstage study, with measures showing no viral activity in 94% of genotype 1 patients on a 12-week course of three experimental compounds: daclatasvir (an NS5A inhibitor), asunaprevir (an NS3 protease inhibitor) and BMS-791325 (NS5B non-nucleoside polymerase inhibitor). The company plans to start Phase III studies of the three-drug combo in 2014.

Japan cases abound
Talk to the proud contenders in the hep C arena, and you'll learn that each one sees his advantage over rivals. With Gilead's ($GILD) annihilation of the virus in a Phase II study that it's taken to Phase III development, analysts see the drug giant as the leader in advancing simple, all-oral regimens to the U.S. market.

However, hep C afflicts patients around the world, has 6 different genotypes and brings a bevy of other variables into the treatment equation, according to Dr. Doug Manion, senior vice president of development for virology at Bristol-Myers Squibb ($BMY). The mixed bag brings opportunities. Take Japan, where Manion believes Bristol could be the first to market with an all-oral regimen, with plans to file for approval of a dual combo of daclatasvir and asunaprevir by end of 2013.
To hear Manion tell it, the Japanese market for hep C drugs is nothing to sneeze at. Japan, where an estimated 2 million people have hep C, has an infected population composed of many elderly patients and mostly genotype 1b cases. The virus spread in large part because of contaminated blood supplies in country.

"These are elderly patients. They are very sensitive to the adverse events of interferon," said Manion, who leads Bristol's development in Japan. "A lot of them have been unwilling to even try a curative regimen that contains interferon. So that's why [the government] is so keen on getting an all-oral regimen there."

Enter Bristol and its all-oral cocktail. If approved in Japan, Bristol's combo could quickly seize market share as those who have forgone interferon-based therapies come off the sidelines to be treated.

Still, many contenders have an argument that buttresses their case for success in the hep C field.

Vertex finds strength in numbers
At Vertex ($VRTX), there are multiple all-oral options on the table, even though none of those options yet involves a Phase III study, which could come in 2014. The Cambridge, MA-based company has been wheeling and dealing since last June, when it struck an exclusive licensing deal with Alios BioPharma that featured a nucleotide polymerase inhibitor called VX-135 (formerly ALS-2200).

Vertex now plans to study VX-135 in four Phase II studies, including one that combines the drug with its fading blockbuster Incivek and another with ribavirin. Two more Phase II studies hit Vertex's drawing board this month when the company revealed two separate agreements with GlaxoSmithKline ($GSK) and Johnson & Johnson's ($JNJ) Janssen to test 135 in combination with GSK's NS5A inhibitor GSK2336805 in one midstage trial and in a dual combo with Janssen's protease inhibitor simeprevir (TMC435) from its partner Medivir.

"Because the efficacy we have no doubt about, the antiviral activity we have no doubt about, it's really generating the safety data to let the [VX-135] program go forward," Dr. Robert Kauffman, Vertex's chief medical officer, said in an interview. The four midstage studies should provide more of that key safety data as well as results on which patient populations respond best to which combos.

Achillion, the lone warrior
Unlike Vertex ($VRTX), Achillion thinks that it could have all the ingredients for a potent all-oral combo for hepatitis C with the three antivirals it's studying in clinical trials.
That's not to say Joseph Truitt, head of business development for Achillion Pharmaceuticals, isn't open to collaborations with other hep C developers, because he says he definitely is. But the New Haven, CT-based company, despite lots of rumors earlier this year that it was buyout bait, could advance an interferon-free cocktail to market alone.

Add to the mix Roche ($RHHBY) and Boehringer Ingelheim, two more of the 20 largest drugmakers in the world that want a piece of the action in hep C. Boehringer is planning to begin a Phase III trial of an all-oral combo for the U.S. market. The herd is large and running fast.
For Vertex, this doesn't leave much time to remain the top act in the industry with Incivek. Many blockbusters generate billions of dollars in annual revenue for a decade or more. But Vertex is already seeing sales of Incivek fade after a year and half on the market.

"Not just crowded, but the speed of change is I think very unique," Dr. Robert Kauffman, Vertex's chief medical officer, said. "It is really quite remarkable and we are very happy to have been at the forefront of this. [Incivek] paved the way for direct-acting antivirals."
-- Ryan McBride (email | Twitter)

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Gilead May Top Rivals With Hepatitis C Therapy Results

Bloomberg News -
By Ryan Flinn and Meg Tirrell on November 13, 2012

Gilead Sciences Inc. (GILD) may have an edge on rivals developing new hepatitis C drugs for a potential $20 billion market after a study showed its experimental drugs cleared the liver disease virus in 100 percent of patients.

The Foster City, California-based company rose to the highest price in its 20 years of trading yesterday on research presented at the meeting of the American Association for the Study of Liver Diseases in Boston. Results showed that combining Gilead’s experimental drugs with a standard medicine cleared the hepatitis C virus in all 25 patients in a 12-week trial.

Abbott Laboratories (ABT) and Bristol-Myers Squibb Co. (BMY) also featured positive results on their hepatitis C drugs at the medical meeting. Still, Gilead’s data “sets a nearly impossible rate for competitors to exceed,” Bret Holley, an analyst with Guggenheim Partners, wrote yesterday in a research note.

“Gilead will likely be the first to market with a simple and efficacious one pill, once-daily regimen,” Michael Yee, an RBC Capital Markets analyst in San Francisco, said in a note.“All this adds up so far to supporting our thesis that Gilead has a $5 billion plus drug.”

Abbott, based in Abbott Park, Illinois, countered with data showing a combination of its therapies rid 87 percent of 79 patients of the virus after 12 weeks of therapy, or 97 percent when given ribavirin. Merck & Co. (MRK), Vertex Pharmaceuticals Inc. (VRTX)and Achillion Pharmaceuticals Inc. (ACHN) are among other drugmakers developing medicines for the liver disease.

Bristol-Myers
Bristol-Myers reported results at the meeting showing that combining three of its experimental medicines -- daclatasvir, asunaprevir and BMS-791325 -- cleared the hepatitis C virus in 94 percent of 16 patients in a trial. The company plans to take the therapy into final-stage trials in 2014.
Hepatitis C affects as many as 170 million people worldwide, according to the World Health Organization. The liver disease is currently treated for as long as a year with injection drugs including interferon, which can be unpleasant to take because of the flu-like symptoms that accompany it. The new drug regimens in testing are designed to be taken as pills, with shorter treatment durations and fewer side effects.

Gilead gained 14 percent at the close yesterday in New York to $73.93, the stock’s highest price since the company first offered shares to the public in 1992. Abbott gained less than 1 percent to $64.87. Bristol-Myers declined less than 1 percent to $31.94.

Abbott Competitive
Abbott’s drug data measured patients 12 weeks after the end of treatment. Gilead’s studies looked at patients four weeks after its therapy ended.

Abbott’s “strong results” keep it competitive with Gilead and position the company to become one of first drugmakers to bring an all-oral hepatitis C treatment to the market, Larry Biegelsen, an analyst with Wells Fargo in New York wrote in a note to clients.

Abbott’s clinical trial included more patients and was conducted in more locations than Gilead’s, making it “slightly lower risk in phase 3,” or the final of three phases of trials typically required for U.S. regulatory approval, Biegelsen said. He said, though, Gilead’s regimen would require three pills a day, versus six for Abbott’s.

The combination regimens from Abbott and Bristol-Myers didn’t include a class of drugs called nucleotide polymerase inhibitors, which have been thought to be a key part of therapy for hepatitis C. The quest for “nucs” led to Gilead’s $10.8 billion purchase of Pharmasset Inc., giving it GS-7977, known as sofosbuvir.

Bristol-Myers also acquired a nucleotide, spending $2.5 billion for Inhibitex Inc. in January. By August, the drugmaker had abandoned the medicine after one patient died and others were hospitalized while taking the drug in a study.

No Nucs
Data presented at the liver meeting suggest regimens not containing nucs may be viable.
“The nuc may not be as sacrosanct as we thought it may have been,” Doug Manion, head of neuroscience and virology research at Bristol-Myers, said in an interview. “It was a big’a-ha!’ moment with our internal triple” combination.
Shares of other drugmakers developing hepatitis C therapies moved on the data presented at the conference.

Achillion, based in New Haven, Connecticut, fell 12 percent to $7.90. Vertex, based in Cambridge, Massachusetts, slid 2.2 percent to $44. Idenix Pharmaceuticals Inc. (IDIX) rose 12 percent to $4.65 after the company said in a statement that its evaluation of its experimental hepatitis C drug, IDX184, found “no evidence of severe cardiac findings.” U.S. regulators had placed the medicine on clinical hold last August after safety concerns arose with Bristol-Myers’s drug.

Vertex Drug
Vertex’s Incivek was approved last year, days after U.S. regulators approved a drug from Whitehouse Station, New Jersey-based Merck. They were the first medicines for hepatitis C to win Food and Drug Administration approval in almost a decade.

“A few years ago, no one thought you could develop a regimen without interferon,” Milind Deshpande, Achillion’s chief scientific officer, said yesterday in an interview at AASLD meeting.
Now, hepatitis C could become the seventh disease in human history to be eradicated, joining others like small pox, said Bristol-Myers’s Manion.

“It’s a whole different paradigm,” he said.

To contact the reporters on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net ; Meg Tirrell in New York at mtirrell@bloomberg.net
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

http://www.businessweek.com/news/2012-11-13/gilead-may-top-rivals-with-hepatitis-c-therapy-results

Hep C Competitors Cede Space To Gilead And Bristol-Myers And Turn To Niche Uses

November 12, 2012

Source-Seeking Alpha

The analyst community might have already written the epitaph for Vertex Pharmaceuticals’ (VRTX) Incivek and Merck & Co’s (MRK) Victrelis, but the search for growth for the two hepatitis C treatments continues apace. The AASLD Liver Meeting became an opportunity for the two companies to showcase potential new uses in hard-to-treat populations.

They were joined by a host of competitors with new agents looking to highlight efficacy in patients such as those who have progressed to fibrosis, cirrhosis or liver transplants. In so doing, developers appear to be acknowledging that Gilead Sciences (GILD), Bristol-Myers Squibb (BMY) or Abbott Laboratories (ABT) are likely to be first to market with the first broadly used all-oral hep C antiviral combination.

The billion-dollar drop

Forecasts for Incivek and Victrelis, the first hep C protease inhibitors that have been able to shorten the standard treatment with interferon and ribavirin, have plunged in the past 12 months on continued clinical success from Gilead’s GS-7977 (Vertex’s hep C plans play second fiddle to cystic fibrosis, September 26, 2012).

The belief is that GS-7977, the nucleoside NS5B polymerase inhibitor known generically as sofosbuvir, can eliminate interferon and side effects that include psychiatric and flu-like symptoms, which discourage many patients from seeking treatments.

Likewise, many of the compounds trailing sofosbuvir, Bristol-Myers’ daclatasvir and Abbott’s ABT-450 have not been given much attention, the belief being that one or more of these will break through and become the blockbuster that gobbles up the market. EvaluatePharma’s consensus forecast for sofosbuvir stands at $5.78bn for 2018, for example.

However, with multiple genotypes, difficult outcomes of untreated disease and growth in emerging markets, there is still much to play for in the space. Thus attention is now turning to patients resistant to treatment in the past or those for whom current therapies are unproven.

With the disease progressing from infection to liver dysfunction, fibrosis, cirrhosis, cancer and transplant – not to mention frequent co-infection with HIV – compounds that can prove to repel the virus during the various stages of the disease will be welcomed by patients and physicians.

The established players

The biggest news came from Vertex and its ex-North America partner Johnson & Johnson, which announced new data on the use of Incivek in HIV co-infected patients, with a backbone of pegylated interferon and ribavirin and HIV anti-retroviral treatments Sustiva or Reyataz. Of patients treated with Incivek, 74% had achieved undetectable hep C viral loads 24 weeks following the end of treatments, compared with 45% of those taking a placebo plus interferon and ribavirin.

Given that 25% of HIV patients in the U.S. are estimated to have a hep C co-infection – common among intravenous drug users with HIV – and the population at greater risk of liver-related disease, failure and death, this could be an important new use for Incivek and help the partners extend its lifecycle.

Data on Victrelis and Incivek in cirrhosis patients were mixed, with an analysis of cirrhotic patients who had never received hep C treatment before, demonstrating that they can successfully complete protease inhibitor therapy if ribavirin doses are reduced or erythropoietin-stimulating agents are used in the event of anaemia. However, a French compassionate-use trial in cirrhotic patients who have failed to respond to treatment suggested that severe adverse events were common in that population when treated with protease inhibitors.

Both Vertex and Merck announced phase I data for follow-on hep C drugs – Vertex’s ALS-2200 is a nucleoside NS5b inhibitor, and Merck has a protease inhibitor in MK-5172 along with the early-stage NS5a inhibitor MK-8742, which could make for a useful combination treatment. But as they are well behind the likes of Gilead, Bristol-Myers and Abbott, stretching out sales for the marketed protease inhibitors would allow both companies to maintain a presence in the space.

The newer agents

Poor treatment responders and those with advanced disease have also been a focus of newer agents, with data on Medivir and J&J’s simeprevir, Roche’s danoprevir, Boehringer Ingelheim’s combination of BI 201335 and BI 207127 along with daclatasvir getting their moments at AASLD.

Ambitiously, Medivir and J&J are pursuing treatment in post-transplant with hepatitis C – data showed that simeprevir had no clinically relevant impact on the blood levels of the immunosuppressives tacrolimus or cyclosporine in healthy participaints.

Danoprevir plus mericitabine, one of the quieter developing combinations in the field, showed that it has potential in patients who have failed or partially responded to earlier treatment: in the Matterhorn study it suppressed the virus 12 weeks after the end of treatment in up to 100% of patients, depending on genotype and previous response, when used in combination with ritonavir, ribavirin and interferon. Lower response rates were reported with an interferon-free regimen.

Like Roche, Boehringer’s combination has also been quietly developing: the private German company detailed an analysis of cirrhotic patients included in its phase II trial of the two drugs with ribavirin – a trial that significantly did not include interferon. Viral suppression was achieved in up to 50% of patients with genotype 1a and 86% of those with genotype 1b.

For now sofosbuvir is at the cutting edge, and while the continued positive news from the Gilead drug has let some of the air out of the hep C bubble, competitors have not given up (Signs are growing that the hep C ship is sailing, August 1, 2012). Success in niche populations could yet be a winning strategy.

http://seekingalpha.com/article/1000741-hep-c-competitors-cede-space-to-gilead-and-bristol-myers-and-turn-to-niche-uses

Gilead, Abbott Unwrap Dueling Hep C Data (Updated)
November 12
Source-The Street
By Adam Feuerstein

BOSTON (TheStreet) -- Gilead Sciences(GILD ) has drawn first blood from Abbott Labs(ABT ) (but just barely) in the battle for hepatitis C pill supremacy.

Twelve weeks of treatment with two Gilead drugs plus the immune system booster ribavirin yielded an interim cure rate of 100% in treatment-naive hepatitis C patients.

A 12-week regimen consisting of three Abbott drugs plus ribavirin demonstrated a final cure rate of 97% of treatment-naive hepatitis C patients and 93% of "null" responders -- the hardest-to-treat patients because they've failed previous therapy.

The score so far: Gilead 100%, Abbott 97%. Close, but Gilead wins, which means shares are likely to move higher when trading opens Monday.

The Gilead result is the "best case" scenario, said ISI Group analyst Mark Schoenebaum in an email to clients.

In a Monday note to clients, Jefferies analyst Thomas Wei said, "These data make us more confident in Gilead winning a dominant position among [genotype 1] regimens for hepatitis C, with comparable cure rates, fewer side effects and better convenience relative to the Abbott regimen."

Gilead shares closed Friday at $65.01.

The Abbott and Gilead regimens were not tested against each other in a single study, so declaring a winner and a loser isn't scientific or fair, necessarily. It's important, too, to note that Abbott's phase II study is larger and reported final cure rates after 12 weeks of follow-up. Gilead's phase II study enrolled fewer patients and cure rates are being reported after only four weeks of follow-up.

Wall Street investors are comparing the two sets of results directly against each other, nonetheless.

Hepatitis C researchers, with investors tagging along, are gathering in Boston at the Liver Meeting, the annual conference sponsored by the American Association for the Study of Liver Disease. The most important data presentations over the next four days will focus on the race to develop new pills, which when used in various combinations, can replace the traditional injections long required to treat and cure hepatitis C.

The hepatitis C drug treatment market could grow to as much as $20 billion, some estimates claim, if more people with the viral liver disease seek cures with simpler and more effective all-oral therapies.

The new Abbott data announced Saturday come from a large, phase IIb study known as "AVIATOR" that was designed to assess the efficacy and safety of various combinations of oral hepatitis drugs in treatment-naive, genotype 1 hepatitis C patients as well as hard-to-treat null responders.

The Abbott drugs studied in AVIATOR were ABT-450, a protease inhibitor that requires blood-boosting with ritonavir; ABT-072, an NS5A inhibitor; and ABT-333, a "non-nuc" polymerase inhibitor. Ribavirin, a current backbone in hepatitis C treatment, was also included in some but not all of the combination regimens.

Gilead's results come from a large phase II study known as ELECTRON, testing two experimental pills, the nucleoside, or "nuc" polymerase inhibitor GS-7977 (also known as sofosbuvir) and GS-5885, an NS5A inhibitor, plus ribavirin. The study also enrolled treatment-naive, genotype 1 hepatitis C patients.

Gilead has already started phase III studies of its oral hepatitis C pill combinations. Positive results could lead to regulatory approval in 2014. Based on the results from AVIATOR, Abbott is moving forward into phase III studies with its three-drug regimen, with and without ribavirin.

In addition to efficacy, convenience may also play a role in which new hepatitis C regimen emerges as the winner. Gilead could have a slight edge because GS-7977 and GS-5885 are being coformulated into single pill taken once per day. With the addition of ribavirin, hepatitis C patients on the Gilead regimen would take two pills in the morning and one at night for 12 weeks. Abbott's combination therapy requires patients to take more pills. With ribavirin added, hepatitis C patients would swallow four pills in the morning and two pills in the evening for 12 weeks.

Vertex Pharmaceuticals(VRTX ), Bristol-Myers Squibb(BMY ), Merck(MRK ), Idenix Pharmaceuticals(IDIX ) and Achillion Pharmaceuticals(ACGN ) are also engaged in the race to develop new, combination-pill therapies against hepatitis C.

-- Reported by Adam Feuerstein in Boston.

November 12, 2012
Gilead Sciences drug combination clears hepatitis C in all patients in Phase II trial
Last Updated:
November 12, 2012 15:56

Shares in Gilead Sciences rose as much as 12 percent Monday after the company reported data from a mid-stage trial at the AASLD annual meeting suggesting that its experimental hepatitis C drugs cleared the virus in 100 percent of treatment-naïve patients. "This is starting to look like a home-run as we now know [Gilead] at least has a 100 percent cure all-oral regimen with its own wholly-owned drug with no partnering," remarked RBC Capital Markets analyst Michael Yee.

In the ELECTRON trial, 25 patients with hepatitis C virus (HCV) genotype 1 were treated with an oral regimen of sofosbuvir, GS-5885 and ribavirin for 12 weeks. In addition to achieving a sustained virological response (SVR) four weeks after completing therapy, the company reported that the drug combination was well tolerated. In a subset of the trial, nine previous null responders were treated with this same combination and the virus was not detected in the three patients who have reached the four-week post-treatment time point. "These results indicate that adding GS-5885 to sofosbuvir-based regimens may enhance SVR rates, potentially offering HCV genotype 1 infected patients a convenient 12-week course of oral therapy," remarked principal study investigator Edward Gane.

Gilead recently initiated a Phase III trial evaluating sofosbuvir and GS-5885 without ribavirin in 800 HCV genotype 1 treatment-naïve patients, 20 percent of whom have evidence of cirrhosis. The four-arm study will evaluate 12- and 24-week courses of the combination therapy.

At the same meeting, Abbott announced that a trio of its medications used in combination with ritonavir cleared the virus in 97.5 percent of treatment-naïve patients and produced "unprecedented" cure rates for patients who failed to benefit from standard treatment. However, Piper Jaffray & Co. analyst M. Ian Somaiya indicated that it was "a clear disadvantage" for Abbott that its regimen requires more drugs than Gilead's planned combination therapy.

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