Hepatitis C Case Study: Interferon-Free Therapy Genotype 1a W-Prior Null Response

Hello everyone, Projects in Knowledge launched a couple new learning activities which provide a look at two different hepatitis C patients, each case study is followed by Paul Y. Kwo, MD.  

The first presentation is a genotype1b treatment-naive patient with cirrhosis. The second is a null responder with stage two fibrosis, a highlight of both presentations is provided below. Like any site offering continuing medical education (CME), it requires a free quick registration.

In addition, Ira M. Jacobson, MD will be hosting a satellite symposium on May 03, 2014; Hepatitis C - Hepatitis C Treatment Goes Viral: Let's Talk About Oral Therapies – Satellite Symposium. This CME/CE activity is designed for hepatologists, gastroenterologists, infectious disease specialists, primary care physicians, nurses, and pharmacists involved in the screening and treatment of patients with HCV or those at risk of acquiring the infection.

P. Kwo, MD
Recently approved direct-acting antiviral agents offer new choices for patients with chronic hepatitis C virus infection, including those with cirrhosis. Join Paul Y. Kwo, MD, for this case study in which he follows a cirrhotic treatment-naive patient with genotype-1b infection from assessment through treatment.

Case Presentation - Patient Assessment 
A 68-year-old Hispanic male presented to you for a discussion of HCV treatment options. He was recently diagnosed with chronic HCV when his physician ordered an HCV screening test in response to the 2012 recommendation by the Centers for Disease Control and Prevention that all individuals born between 1945 and 1965 be tested for HCV, regardless of other risk factors.10 He likely acquired the infection approximately 30 years ago from a blood transfusion while in the military. His past medical history includes arthritis, hyperlipidemia, and diabetes, treated with ibuprofen, atorvastatin, and metformin, respectively. He is currently retired but travels extensively with his wife to visit their grandchildren. Follow-up HCV testing showed genotype-1b infection and a viral load of 6.2 million copies/mL. An imaging study and ultrasound of his liver demonstrated a nodular liver with mild splenomegaly. Endoscopy demonstrated small esophageal varices. Blood work showed a hemoglobin level of 13.2 g/dL, a platelet count of 108,000/mm3, an aspartate aminotransferase of 94 IU/L, and an alanine aminotransferase of 79 IU/L. Physical examination was normal. His blood pressure was 128/70 mmHg, respirations 16. There was no hepatomegaly or splenomegaly. He had mild central obesity (94 kg), no muscle wasting, and no palmar erythema.

Published on April 23, 2014
Phase II data from emerging all-oral direct-acting antiviral regimens show high rates of sustained virologic response (SVR), even in patients with prior null response to peginterferon-based therapy. Join Paul Y. Kwo, MD, for this case study in which he identifies a null responder who elects to enroll in a phase III trial of an interferon-free regimen that includes more than one drug class. In addition, Dr. Kwo provides preliminary SVR12 data for multiple emerging regimens in this hard-to-treat patient population.

Case Presentation - Patient Assessment 
A 50-year-old male presents to your practice to discuss the potential of starting treatment for genotype-1a HCV infection. In 2009 he had a null response to peginterferon/ribavirin, with his viral load dropping only 1 log at 12 weeks, from 10 million IU/mL pretreatment to 1.2 million IU/mL. His baseline liver biopsy at that time showed stage 2 fibrosis. He reported missing no doses but found the therapy difficult to tolerate. He experienced fatigue and increasingly painful injection-site reactions. Most importantly, he found it difficult to concentrate at his full-time job as a contractor and had to turn over major projects to his partner. He feels reasonably well now, with only occasional right upper quadrant pain. He takes lisinopril 20 mg for hypertension and ibuprofen 800 mg on an as-needed basis. On physical exam he is a slightly overweight male, with a weight of 120 kg. His vitals are otherwise stable with blood pressure of 130/88 mmHg. Other than mild hepatomegaly, his exam is normal. Laboratory tests show: hemoglobin14 g/dL, platelet count of 169,000/mm3, aspartate aminotransferase 112 U/L, alanine aminotransferase 115 U/L, total bilirubin 1.2 mg/dL. His Fibroscan® demonstrates liver stiffness of 12 kPa. An ultrasound shows mild hepatomegaly and fatty infiltration, with mild splenomegaly.
Published on March 31, 2014 

I. Jacobson, MD
Register today! Join us at this compelling satellite symposium for informative and interactive expert-guided presentations on the current state of oral therapies for chronic hepatitis C virus (HCV) infection, the implications of clinical trial results, and how the latest advances are affecting today’s real-world clinical practice.

This program is not affiliated with Digestive Disease Week®. 
ViralEd just released an 1.5-hour Internet symposium discussing key data presented at the 49th Annual Meeting of the European Association for the Study of the Liver (49th EASL) which took place this month in London, England.

Aetna CFO says spent $30 mln on Sovaldi in Q1, as expected

Aetna CFO says spent $30 mln on Sovaldi in Q1, as expected
April 24 Thu Apr 24, 2014 7:00pm IST

(Reuters) - Aetna Inc. spent about $30 million during the first quarter on Sovaldi, the pricey new hepatitis C treatment from Gilead Sciences Inc., Chief Financial Officer Shawn Guertin said on Thursday during a conference call with investors.

Guertin said the costs were in line with the company's expectations. Most of it was in its commercial business and in Medicare Part D, the government program in which private insurers manage drug benefits.

Medicaid-related Sovaldi costs accounted for the smallest portion of that $30 million, he said, as some states continue to develop policies on the drug and because some states where it operates do not use private insurance to pay for any pharmaceutical benefits. (Reporting by Caroline Humer; Editing by Chizu Nomiyama)

Source - Reuters

Sovaldi PBS Video :Report on Gilead's profits, coverage and costs



A new drug has a 90 to 100 percent chance of curing the Hepatitis-C virus, but costs tens of thousands of dollars for a course of treatment. The announcement by the manufacturer that it earned more than $2 billion in the year’s first quarter raises the question, who should pay when drugs are highly effective, but extremely expensive? Hari Sreenivasan reports on the profits, coverage and costs.

TRANSCRIPT

JUDY WOODRUFF: Now: Who should pay when drugs are very effective, but extremely expensive?
That’s an important question for the U.S. health care system as new treatments come along, and it’s a matter of real concern over a new drug that has a 90 percent to 100 percent chance of curing the hepatitis C virus. Its manufacturer announced record sales yesterday of more than $2 billion in just the first quarter of the year. Profits, coverage and costs are all at issue, as Hari Sreenivasan reports.
HARI SREENIVASAN: Kim Bossley knows how fragile life can be. In 2005, Bossley was diagnosed with hepatitis C, a blood-borne virus that can destroy the body’s liver.
KIM BOSSLEY: I went from stage one to stage four, decomposed liver, very quickly.
HARI SREENIVASAN: News of her rapidly declining health was devastating for the 46-year-old mother of two.
KIM BOSSLEY: You fall into a depression when you’re diagnosed with hep C. Your own mortality rate hits you.
DR. GREGORY T. EVERSON, University of Colorado Hospital: That’s a pretty good response.
HARI SREENIVASAN: This fall, after nine years of battling the virus, Kim Bossley was accepted into a treatment trial with a new drug called Sovaldi.
DR. GREGORY T. EVERSON: So, Kim, we will check your labs here.
HARI SREENIVASAN: Almost immediately after taking Sovaldi, the hepatitis C virus disappeared.
DR. GREGORY T. EVERSON: Not detected, not detected, not detected.
HARI SREENIVASAN: Bossley’s doctor, Gregory Everson, is an expert on the hepatitis C virus. He says results with Sovaldi are remarkable.
DR. GREGORY T. EVERSON: Do you feel like you can do what you want to do on this treatment?
KIM BOSSLEY: Yes.
DR. GREGORY T. EVERSON: Yes.
HARI SREENIVASAN: A hepatologist at the University of Colorado hospital, Everson has treated some 200 patients with the new drug.
DR. GREGORY T. EVERSON: Kim’s response is typical. Her viral load was in the millions — within a week or two, undetectable. That is what we’re seeing in almost all the patients we’re treating today. It’s really quite extraordinary.
HARI SREENIVASAN: In fact, across the United States, hepatitis C patients are experiencing the same dramatic results, so much so that Dr. Everson calls the new drug manufactured by Gilead Sciences a game-changer.
DR. GREGORY T. EVERSON: We’re not talking about chronic disease anymore. We’re talking about getting rid of the infection completely. We’re talking about a complete cure rate.
HARI SREENIVASAN: And that is welcome news for the three million Americans infected with the hepatitis virus, 25 percent of whom are projected to die from it.
Even better news, in December, the Food and Drug Administration approved Sovaldi. But as spectacular as Sovaldi appears to be, so too is its price tag. Each pill is $1,000. And at a typical treatment of 120 days, the drug’s extraordinary cost has raised concerns.
MATT SALO, National Association of Medical Directors: The new development is simultaneously very exciting in terms of its efficacy, but potentially very, very frightening in terms of its cost, because we’re talking about a nexus of a drug that is, on the face of it, very expensive.
HARI SREENIVASAN: Matt Salo heads the National Association of Medicaid Directors. He says states are scrambling to figure out how to pay for Sovaldi with government-funded insurance, particularly when existing drugs are 50 to 70 percent effective.
MATT SALO: Medicaid is actually kind of used to dealing with pharmaceutical treatments that are very expensive, but for small numbers of people. With hepatitis C, we know there are at least three million people and potentially as many as five million people in this country who have hepatitis C.
So when you multiply those two, you are really looking at a game-changer in terms of cost.
WOMAN: One a day of that one.
HARI SREENIVASAN: Kim Bossley’s treatments are free because she’s part of the study for those with advanced liver disease. And while she agrees the drug’s price tag is high, she says the combination of drugs she used before Sovaldi, interferon and ribavirin, were extremely rough.
KIM BOSSLEY: There is no comparison.
HARI SREENIVASAN: Her previous drug treatment, she says, caused exhaustion, depression and hair loss.
KIM BOSSLEY: It is a very harsh regimen. It’s very debilitating.
HARI SREENIVASAN: In fact, Dr. Everson said the existing drug treatments are so tough on his patients, many hepatitis C sufferers avoid them altogether.
DR. GREGORY T. EVERSON: Most patients didn’t even want the treatments because of the side effects. People wouldn’t even come for treatment. They wouldn’t get their hepatitis C addressed.
HARI SREENIVASAN: And beyond the physical costs, Everson says there is a price for in the curing the virus.
DR. GREGORY T. EVERSON: It’s one of the costliest diseases when you get to the end stages, where people start to have complications of cirrhosis.
HARI SREENIVASAN: That point is echoed by John McHutchison, executive vice president at Gilead Sciences.
JOHN MCHUTCHISON, Gilead Sciences, Inc.: The costs of caring for patients with hepatitis C are not all up front. So whilst it might be expensive to treat somebody up front now, by curing somebody, you are preventing the costs of care of that patient later on, so, as their disease progresses over time, the cost of liver transplant, the cost of caring for somebody with liver cancer.
So if you can treat more people, and spend those dollars up front to cure those people, in the long-term, and over the long-term horizon, you will save the costs to the health care system.
NARRATOR: If you are one of the millions of people with hepatitis C, you haven’t been forgotten.
HARI SREENIVASAN: But while Gilead calls Sovaldi a cure, it is not a vaccine. Hepatitis C, which is transmitted through blood, can be contracted more than once. The most common way to get the virus is through I.V. drug use.
MATT SALO: One of the things to keep in mind with Sovaldi is that this is not an immunization. This doesn’t make someone hepatitis-free forever. And if you got hepatitis C because of certain risky behaviors and you go and you get, in effect, cured, there is nothing to prevent from you getting it again if you relapse back into those same behaviors.
HARI SREENIVASAN: Kim Bossley contracted the virus from a blood transfusion at her birth. Bossley was the first baby born to a mother who had undergone a kidney transplant. She was featured in “Good Housekeeping” magazine as a miracle baby. During the birth, Kim’s mother received a transfusion of blood infected with hepatitis C.
But neither knew they had the virus until getting sick later in life. Bossley’s mother ended up dying from the condition, something that makes Kim’s own condition even tougher.
KIM BOSSLEY: Seeing my mom suffer through the latter part of her stages, it really took a lot out of me, to the point where I finally had to — you know, this is not how mom or I want to live. You know, I want to fight. I want to find a cure.
HARI SREENIVASAN: As new sophisticated drugs to treat all kinds of conditions enter the market, Matt Salo says the question of costs will likely arise again.
MATT SALO: It’s not a Sovaldi question, per se, because this really is the tip of the iceberg. There are so many other drugs that have the potential of bringing on one hand, you know, incredible improvements in human life and health and well-being, but on the other hand extraordinary costs.
HARI SREENIVASAN: Salo would like to see a national dialogue about what insurers should cover.
MATT SALO: I think it is critically important that we start having that conversation about, how do we value health, what price health, and what price pharmaceuticals? I think this is an important conversation we need to have.
HARI SREENIVASAN: For her part, Kim Bossley has started a foundation to hep offset drug costs for other hepatitis patients.
GWEN IFILL: Online, you can read about how free samples can influence what doctors prescribe to their patients. That’s on our health page.

Source - PBS

Vitamin D – should you take it?

Egg yolks contain a small amount of vitamin D istockphoto.comVitamin D – should you take it? 
By Lindsay Kobayashi
Posted: April 24, 2014

Egg yolks contain a small amount of vitamin D
iStockphoto.com

My hunch is that it depends. Vitamin D is a nutrient that helps our bodies regulate the metabolism of calcium and phosphate (1). Most vitamin D comes from sunlight, while it is also found in certain foods including fatty fish, mushrooms, egg yolks, vitamin-D fortified foods. For example, milk in many countries is always fortified with vitamin D, and some brands of breakfast cereals and orange juice are fortified as well (2).  Vitamin D can also be obtained through taking vitamin D supplements found at your local grocery or health food store. The classic health consequences of inadequate vitamin D are rickets in children, and low bone mineral density and osteoporosis in older adults (3). Low vitamin D has also been associated with increased risk for many other health conditions including breast, prostate, and colorectal cancer, multiple sclerosis, and cardiovascular disease (4-6). However, the quality of scientific evidence for these relationships varies because it is actually quite challenging methodologically to study the cause-effect relationship of vitamin D on health.

Because definitive high-quality evidence is lacking, the actual beneficial effect of vitamin D on health has been heavily debated in recent years. Like many other dietary or lifestyle factors that have been linked to health outcomes with scientific uncertainty (examples: coffee, alcohol, vitamin C, herbal supplements), the available information about whether to take vitamin D supplements can be very confusing. Here is where we stand right now:

In 2011, the American Institute of Medicine released an expert report on the dietary reference intakes for vitamin D (3). They stated that, for people aged 1 to 70 years old including pregnant and lactating women, the recommended dietary allowance (RDA) is 600 IU per day of vitamin D. For adults aged over 70 years the RDA is 800 IU per day. Intake should not exceed 4000 IU per day for people aged 9 years and over. The full RDA guidelines can be found here. Interestingly, their expert panel concluded that current scientific evidence is insufficient to conclude that vitamin D plays a causal role in non-bone-related health conditions (3). Now, this statement may or may not mean that vitamin D has no effect on health aside from bone conditions, simply that our current knowledge is insufficient.

Supplements can be a good source of vitamin D

iStockphoto.com
Supplements can be a good source of vitamin D istockphoto.comFast forward to today, and it doesn’t seem like our evidence base has evolved much. An ‘umbrella’ review of evidence on the link between blood plasma concentrations of vitamin D and 137 unique health outcomes was published in the British Medical Journal earlier this month (7). The review was the largest synthesis of knowledge to date, and the authors unfortunately had to conclude that:
“Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable”
The authors concluded that vitamin D supplementation is probably linked to decreased dental caries (cavities) in children, reduced parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis, and to an increase in maternal vitamin D concentrations at term, and an increase in birth weight (7). These are very specific conditions that apply only to children, pregnant mothers, and chronic kidney disease patients. The authors also concluded that the evidence is ‘suggestive’ for a correlation between higher blood vitamin D concentrations and a lower risk of several conditions including colorectal cancer, non-vertebral fractures, cardiovascular diseases, depression, high body mass index, and type 2 diabetes (7). However, a major point to note is that these are correlations, which means that although vitamin D has been associated with these health conditions, it may not cause them. Because of the limitations of current research, including the difficulty in measuring the actual vitamin D intake of people, and how much of this actually gets absorbed and has a biological effect, the timing between vitamin D intake and disease onset, and determining the actual dose of vitamin D that may protect against disease, we don’t have definitive answers right now.

So, what should we do about our own health? It is clearly too soon to make any strong recommendations about population-level vitamin D supplementation. Following the current RDA for vitamin D is good, and achieving this level for yourself may include supplementation if you don’t eat many foods containing vitamin D. Always talk to your family physician if you have any concerns about your own health or vitamin D intake. And finally, as always, keep yourself informed with high quality information to make decisions for your own health.

References
1)      National Health Service. Vitamins and minerals – vitamin D. http://www.nhs.uk/Conditions/vitamins-minerals/Pages/Vitamin-D.aspx (accessed 21 April 2014).
2)      National Institutes of Health. Vitamin D: Fact sheet for consumers. http://ods.od.nih.gov/factsheets/VitaminD-QuickFacts/#h3 (accessed 21 April 2014).
3)      Committee to Review Dietary References Intakes for Vitamin D and Calcium, Institute of Medicine: Dietary Reference Intakes for Calcium and Vitamin D. Edited by Ross AC, Taylor CL, Yaktine AL, Del Valle HB. Washington, DC: The National Academies Press; 2011.
4)      Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81.
5)      Munger KL, Zhang SM, O’Reilly E, Hernán MA, Olek MJ, Willett WC, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology 2004;62(1):60-5.
6)      Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008;117:503-11.
7)      Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JPA. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ2014;348:g2035

Source PLOS Blogs

Gilead’s Medicine Sovaldi Beats Estimates by $1 Billion




Gilead Revenue Soars on Hepatitis C Drug

 

Record sales of a new hepatitis C drug pushed the first-quarter earnings of Gilead Sciences far beyond expectations, the company reported on Tuesday, but could also heighten concerns about the high cost of the drug, known as Sovaldi, and the ability of the health care system to pay for it.

“If cost were not a factor, we would want to treat the entire population,” said Dr. Rena Fox, a professor of medicine at the University of California, San Francisco. She said it was frustrating that “we finally get this great treatment and then we withhold it.”

Continue reading.......

Gilead’s Medicine Sovaldi Beats Estimates by $1 Billion
April 23, 2014

Gilead Sciences Inc. (GILD:US) overwhelmed sales estimates for its new blockbuster hepatitis C pill in what analysts called the biggest drug start ever, raising questions about insurers’ ability to slow the use of the costly therapy. The shares gained in early trading. 

Sovaldi, the company’s $1,000-a-pill medicine to treat hepatitis C, had sales of $2.27 billion in the first quarter, the company said in a statement. That beat an average of analyst estimates by more than $1 billion. The Foster City, California-based company also reported profit excluding certain items of $1.48 a share, beating by 56 cents the analysts’ average estimate (GILD:US).

The hepatitis C sales are “above even the high end of buy-side expectations,” Mark Schoenebaum, an analyst with ISI Group LLC in New York, said in a note to clients. He called it the best drug introduction in history. Gilead, the world’s biggest makers of HIV drugs, yesterday reported total first-quarter revenue of $5 billion.

Continue reading.......
 

CAIRO - New drug for hepatitis C ‘Sovaldi’ to be available by July

New drug for hepatitis C ‘Sovaldi’ to be available by July

By SARA OSAMA SHOUREAP

CAIRO: “Solvadi”, a new drug formulated to combat hepatitis C, is expected to be released in Egypt starting in July, following registration with the Central Administration of Pharmacist Affairs, said member of the National Committee for Combating Hepatitis C Gamal Essmat on Wednesday.

Essmat told Youm7 that they agreed with Gilead, the company that will produce Sovaldi, to prepare 600,000 doses for an estimated 300,000 patients in Egypt during three stages this year.

The Ministry of Health and the company have officially signed an agreement to provide the new drug for a price 99 percent cheaper than the price on the international market, Essmat added.

On March 12, Minister of Health Adel Adawy declared in a statement that the negotiations between the ministry and the American company were successful and Egypt will obtain the drug for only 1 percent of its price internationally, according to Al-Masry Al-Youm.

Adawy said the price of a one-month prescription in Egypt will cost $300 while in the U.S. it costs $28,000 a month. The full course will cost $13,000 instead of the $168,000 it costs in the U.S.

It is expected that the company will allocate the production line to the Ministry of Health to produce and regulate the product.

The high price of the drug produced by Gilead has sparked anger among people in different countries, according to Reuters.

Former Minister of Health Maha Rabat headed Egypt’s delegation in meetings with the executive board of the World Health Organization (WHO), where they discussed the price of the drug, Egypt representative to the United Nations in Geneva Walid Mahmoud Abdel Nasser said in a Ministry of Foreign Affairs statement last February.

Rabat held meetings with the heads of the executive board member countries, senior officials in the WHO and representatives of the International Alliance against Viral Hepatitis Diseases, Doctors without Borders and the Organization of Patents for Medicines.

According to Nasser, they agreed to support making hepatitis c a top priority and to intensify efforts to provide the required medicine at “affordable prices”.

According to Reuters, Gilead said on March 22 that it was “pleased to have finalized an agreement” to provide the cure to Egypt, one of the countries with the highest rate of hepatitis C patients.

Gregg Alton, the head of corporate and medical affairs at Gilead, said in a statement that “We believe Sovaldi could have a major impact on public health in Egypt by significantly increasing the number of people who can be cured of hepatitis C,” according to Reuters.

Additionally reporting by Dana al-Hadedy.
Source

AbbVie, Enanta’s collaboration partner for ABT-450, has submitted (NDA) to the FDA for interferon-free regimen

Investment Commentary

AbbVie heads to the FDA with its hep C combo in a race with Gilead, Merck
April 22, 2014 | By  


Press Release

Enanta Pharmaceuticals Announces New Drug Application Submission to the U.S. FDA for All-Oral, Interferon-Free Hepatitis C 

Regimen Filing Triggers Milestone Payment to Enanta

AbbVie’s submission to FDA triggers $20 million milestone payment to Enanta

Regimen includes Enanta’s and AbbVie’s protease inhibitor ABT-450



WATERTOWN, Mass.--()--Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a research and development-focused biotechnology company dedicated to creating small molecule drugs in the infectious disease field, today announced that AbbVie, Enanta’s collaboration partner for ABT-450, has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking approval for an investigational, all-oral, interferon-free regimen for the treatment of adult patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection.

“No all-oral therapy has yet been approved to treat GT1 HCV infection, which is estimated to affect approximately 70% of the 3.2 million people of the U.S. population infected with HCV.”

The three direct-acting antiviral regimen consists of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333. ABT-450 is the lead protease inhibitor developed through Enanta’s collaboration with AbbVie.

The U.S. NDA filing triggers a $20 million milestone payment to Enanta from AbbVie. AbbVie also plans to submit applications for regulatory approval of its regimen in the European Union in early May. Enanta is entitled to receive an additional $20 million upon the first regulatory filing in the European Union for a regimen containing a collaboration compound.

The NDA is supported by AbbVie’s data from the largest all-oral, interferon-free clinical program in GT1 patients conducted to date,1 with six phase 3 studies that included more than 2,300 patients in over 25 countries.

“This submission marks a very significant step toward Enanta being part of the first wave of all-oral therapies that may be approved to treat patients with genotype 1 hepatitis C virus,” stated Jay R. Luly, Ph.D., Enanta’s President and Chief Executive Officer. “No all-oral therapy has yet been approved to treat GT1 HCV infection, which is estimated to affect approximately 70% of the 3.2 million people of the U.S. population infected with HCV.”2

In May of 2013, AbbVie's investigational direct-acting antiviral (DAA) regimen with and without ribavirin for HCV genotype 1 was designated as a Breakthrough Therapy by the U.S. FDA. This designation is intended to help expedite the development of drugs for serious or life-threatening conditions and is based in part on preliminary clinical evidence demonstrating a drug or regimen may have substantial improvement on at least one clinically significant endpoint compared to available therapy. 

Protease Inhibitor Collaboration with AbbVie
In December 2006, Enanta and Abbott announced a worldwide agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors and HCV protease inhibitor-containing drug combinations. ABT-450 is a protease inhibitor identified as a lead compound through the collaboration. Under the agreement, AbbVie is responsible for all development and commercialization activities for ABT-450. Enanta received $57 million in connection with signing the collaboration agreement, has received $55 million in subsequent clinical milestone payments, is entitled to receive $20 million in connection with the NDA filing in the U.S. described above, and is eligible to receive up to an additional $175 million in payments for regulatory and commercialization milestones, as well as double-digit royalties worldwide on any revenue allocable to the collaboration’s protease inhibitors. Also, for any additional collaborative HCV protease inhibitor product candidate developed under the agreement, Enanta holds an option to modify the U.S. portion of it rights to receive milestone payments and worldwide royalties. With this option, Enanta can fund 40 percent of U.S. development costs and U.S. commercialization efforts (sales and promotion costs) for the additional protease inhibitor in exchange for 40 percent of any U.S. profits ultimately achieved after regulatory approval, instead of receiving payments for U.S. commercial regulatory approval milestones and royalties on U.S. sales of that protease inhibitor. 

About ABT-450
ABT-450 is an NS3 protease inhibitor discovered through Enanta’s ongoing collaboration with AbbVie. AbbVie and Enanta have an agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors. Protease inhibitors play an essential role in the viral life cycle of the hepatitis C virus (HCV). Inhibition of the protease prevents non-structural (NS) proteins from forming and thereby prevents replication and survival of the HCV virus. ABT-450 is part of AbbVie’s investigational regimen for HCV that consists of boosted protease inhibitor ABT-450/ritonavir (referred to as ABT-450/r), NS5A inhibitor ABT-267 and non-nucleoside polymerase inhibitor ABT-333. 

About Enanta
Enanta Pharmaceuticals is a research and development-focused biotechnology company that uses its robust chemistry-driven approach and drug discovery capabilities to create small molecule drugs in the infectious disease field. Enanta is discovering, and in some cases developing, novel inhibitors designed for use against the hepatitis C virus (HCV). These inhibitors include members of the direct acting antiviral (DAA) inhibitor classes – protease (partnered with AbbVie), NS5A (partnered with Novartis) and nucleotide polymerase – as well as a host-targeted antiviral (HTA) inhibitor class targeted against cyclophilin. Additionally, Enanta has created a new class of antibiotics, called Bicyclolides, for the treatment of multi-drug resistant bacteria, with a focus on developing an intravenous and oral treatment for hospital and community MRSA (methicillin-resistant Staphylococcus aureus) infections.

Related
Retreatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin
A phase 2b study involving patients with HCV genotype 1 infection who had a null response to prior therapy with peginterferon–ribavirin showed that the rate of sustained virologic response to 12 weeks of treatment with ABT-450/r, ombitasvir, dasabuvir, and ribavirin was 93% 24 weeks after the end of treatment.14 We report the results of SAPPHIRE-II, an international, randomized, placebo-controlled, double-blind, phase 3 trial assessing the efficacy and safety of 12 weeks of the all-oral regimen of ABT-450/r–ombitasvir and dasabuvir with ribavirin in patients with HCV genotype 1 infection and no cirrhosis who had received previous treatment with peginterferon–ribavirin.

ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin for Hepatitis C with Cirrhosis
Interferon-containing regimens for the treatment of hepatitis C virus (HCV) infection are associated with increased toxic effects in patients who also have cirrhosis. We evaluated the interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the NS5A inhibitor ombitasvir (ABT-267), the nonnucleoside polymerase inhibitor dasabuvir (ABT-333), and ribavirin in an open-label phase 3 trial involving previously untreated and previously treated adults with HCV genotype 1 infection and compensated cirrhosis.