Wednesday, December 18, 2013

Gilead's Sofosbuvir and Ledipasvir Outstanding Late-stage Hepatitis C Data

Of interest
Feb 10 2014
Gilead Files for U.S. Approval:Ledipasvir/Sofosbuvir Fixed-Dose Combo For Genotype 1 Hepatitis C

Dec 19
Gilead's $1,000 Pill Could Eradicate Hepatitis C, But Ethical And Financial Challenges Loom

Matthew Herper
Forbes Staff
Gilead Sciences' GILD -0.37% two-drug combo pill against hepatitis C is so effective, Wall Street analysts say, that it’s possible that public health officials could begin thinking about eradicating the liver-damaging virus, which may afflict 3.2 million Americans and is spread mostly through sharing needles and needle stick injuries, according to the Centers for Disease Control & Prevention. In some of them, like the musician Lou Reed, it leads to liver failure and death. Gilead’s pill could become one of the best-selling medicines in history.....

Stellar hepatitis C data puts Gilead farther ahead of pack

By Ransdell Pierson and Bill Berkrot

Wed Dec 18, 2013 1:34pm EST

(Reuters) - Gilead Sciences Inc released impressive late-stage data for its once-daily combination pill to treat hepatitis C, advancing its lead in the race to develop new, all-oral treatments for the liver disease, and pushed up its timeline for seeking U.S. approval.

Gilead on Wednesday unveiled initial results from three Phase III studies that demonstrated cure rates well in excess of 90 percent with as little as 8 weeks of treatment for some patients.

The findings were achieved without the use of either injectable interferon, which causes miserable flu-like symptoms, or ribavirin, an antiviral pill that carries its own troublesome side effects.

The tough-to-tolerate older drugs have led thousands of patients to delay treatment for the potentially fatal disease and await new options.

"The results certainly raise the bar and dim the outlook for competitors such as AbbVie, Bristol and Boehringer Ingelheim," Sanford Bernstein analyst Geoffrey Porges has said of rival all-oral programs in development that require more drugs and more pills than Gilead's to achieve similarly high cure rates.

Porges, saying the new data could spell the end of ribavirin use and greatly expand the number of people seeking treatment, raised his peak sales forecast for Gilead's combination to an eye-popping $16 billion in 2016, declining to $6.8 billion by 2020 as the backlog of patients awaiting treatment declines.

Gilead said it would file in the first quarter of 2014 for U.S. approval of the combination treatment that pairs its just-approved Sovaldi (sofosbuvir) and its experimental ledipasvir. The company previously said it would seek marketing approval in the first half of next year.

The Phase III trials tested the combination pill in subjects with the most common, but hardest to treat, genotype 1 strain of the liver virus in both previously untreated patients and those who had failed to be helped by prior treatment. They also included difficult to treat patients with cirrhosis, who tend to be farther along in the liver-destroying disease.

Gilead shares rose more than 2 percent on the favorable new data and the likelihood of a speedier approval from the U.S. Food and Drug Administration.

"We see (trial) results and a more-convenient regimen bolstering Gilead's market prospects over rivals, and expect FDA approval for this regimen before the end of 2014," S&P Capital IQ said in a research report.


Sovaldi, which costs about $84,000 for a course of treatment, belongs to a class of drugs known as nucleotide analog polymerase inhibitors, or "nukes," designed to block an enzyme the hepatitis C virus needs to copy itself. Ledipasvir belongs to a promising new class of drugs that work by blocking the NS5A protein, which the virus also needs to replicate.

Current standard regimens include both interferon and ribavirin and must be taken for 24 to 48 weeks, curing about 75 percent of patients.

Gilead tested its combo pill at a variety of treatment durations both with and without ribavirin. But the high cure rates without ribavirin, which can cause rash, anemia and other side effects, are likely to grab most of the attention of physicians and investors.

In a study of 647 previously untreated patients without cirrhosis called ION-3, 94 percent achieved sustained virologic response (SVR), which is considered cured, after just 8 weeks of treatment, rising to 95.4 percent with a 12-week regimen.

In ION 2 - a trial of 440 more difficult to treat patients who were not cured by prior treatment, including 88 cirrhotics - 93.6 percent were cured by the once daily pill after 12 weeks, while the cure rate rose to 99.1 percent with 24 weeks of treatment.

In ION-1, which looked at 865 previously untreated patients, including 136 with cirrhosis, the Gilead pill cured 97.7 percent with 12 weeks of therapy.

"In general, the data position Gilead to dominate the genotype 1 landscape," ISI Group analyst Mark Schoenebaum said in a research note. He noted that Gilead's ribavirin-free regimen involved one pill once a day, while AbbVie's is six pills a day with ribavirin and four pills without, and includes a medicine that may interact with other drugs.

Genotype 1 accounts for about 70 percent of U.S. infections. Hepatitis C affects an estimated 170 million people worldwide, and if left untreated can lead to cirrhosis, liver cancer, or the need for a new liver.

Bernstein's Porges has said given the convenience and cure rates of the new drugs, the hepatitis C conversation is likely to change from disease management to eradication.

"This is going to be very tempting for people to say, 'We can lick this'," Porges said. But he noted that demand for the drug will eventually decline as patients are cured.

"The long-term economics of curing patients is not good for the drug industry, but it's totally great for society."

(Additional reporting by Caroline Humer; Editing by Gerald E. McCormick, Theodore d'Afflisio and Cynthia Osterman)

Press Release

Gilead Announces SVR12 Rates From Three Phase 3 Studies Evaluating a Once-Daily Fixed-Dose Combination of Sofosbuvir and Ledipasvir for Genotype 1 Hepatitis C Patients

-- High Cure Rates Observed with Single Tablet Regimen May Eliminate Interferon and Ribavirin from HCV Therapy for Genotype 1 Patients -- 

 -- U.S. NDA Submission Planned for Q1 2014--
FOSTER CITY, Calif.--(BUSINESS WIRE)--Dec. 18, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced topline results from three Phase 3 clinical trials (ION-1, ION-2 and ION-3) evaluating the investigational once-daily fixed-dose combination of the nucleotide analog polymerase inhibitor sofosbuvir (SOF) 400 mg and the NS5A inhibitor ledipasvir (LDV) 90 mg, with and without ribavirin (RBV), for the treatment of genotype 1 chronic hepatitis C virus (HCV) infection.
Across the three studies, 1,952 patients with genotype 1 HCV infection were randomized to receive SOF/LDV with or without RBV for eight, 12 or 24 weeks of therapy. Of these, 1,512 patients were treatment-naïve, 440 were treatment experienced and 224 had compensated cirrhosis.
The intent-to-treat SVR12 rates observed to date in the ION studies are summarized in the table below. Results of the 24-week arms from ION-1 will be available in the first quarter of 2014 and will be presented at a future scientific meeting. 

Of the 1,518 patients randomized to the 12-week arms of ION-1 and to all arms of ION-2 and ION-3, 1,456 patients (95.9 percent) achieved the primary efficacy endpoint of SVR12. Of the 62 patients (4.1 percent) who failed to achieve SVR12, 36 patients (2.4 percent) experienced virologic failure: 35 due to relapse and only one patient due to on-treatment breakthrough (with documented non-compliance). Twenty-six patients (1.7 percent) were lost to follow-up or withdrew consent.  

Fewer adverse events were observed in the RBV-free, fixed-dose combination arms compared to the RBV-containing arms in all ION studies. Adverse events observed in those taking the SOF/LDV tablet were generally mild and included fatigue and headache. In the RBV-containing arms of the ION studies, the most common adverse events were fatigue, headache, nausea and insomnia. Anemia, which is a common side effect associated with RBV, was reported in 0.5 percent of patients in the SOF/LDV arms versus 9.2 percent of patients in the RBV-containing arms. Less than 1 percent of patients in the studies discontinued treatment due to treatment-emergent adverse events.

“The results of the ION studies demonstrate that a simple, safe and short course of therapy with a single tablet regimen of sofosbuvir/ledipasvir can provide high cure rates among patients with genotype 1 HCV infection, while eliminating the need for both interferon and ribavirin,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer. “With the availability of these results, Gilead is finalizing its regulatory filing for sofosbuvir/ledipasvir, with the goal of submitting a New Drug Application in the first quarter of 2014.”    

The FDA has assigned the SOF/LDV fixed-dose combination a Breakthrough Therapy designation, which is granted to investigational medicines that may offer major advances in treatment over existing options. Sofosbuvir was approved as Sovaldi™ in the United States on December 6 and in Canada on December 13. Applications are pending in the European Union, Australia and New Zealand, Switzerland and Turkey.    

About the ION Studies

The Phase 3 ION studies are randomized, open-label Phase 3 clinical trials evaluating the efficacy and safety of a once-daily fixed-dose combination of SOF/LDV for 8, 12 or 24 weeks, with and without RBV, among 1,952 genotype 1 HCV patients. The studies included patients who were treatment-naïve or who had failed previous treatment, including protease inhibitor-based regimens. The primary endpoint for each study was SVR12. Complete results from all three studies will be presented at a future scientific conference.    

In ION-1, 865 treatment-naïve genotype 1 HCV patients, including those with cirrhosis, received SOF/LDV with or without RBV for 12 or 24 weeks. In March 2013, a planned review by the study’s Data and Safety Monitoring Board (DSMB) of interim safety and efficacy data from an initial enrollment of patients concluded that the trial should continue without modification. Enrollment of the remaining patients was completed in May 2013. Prior to the DSMB meeting, the statistical analysis plan was amended to allow for the analysis of the primary efficacy endpoint for the two 12-week arms, independent of the 24-week arms. Per the amendment, if SVR12 rates in the 12-week arms were >90 percent (including among those with cirrhosis), early regulatory filings could be pursued, given that longer treatment durations would not be able to show statistically significantly higher SVR12 rates.    

The ION-2 study evaluated 440 treatment-experienced genotype 1 HCV patients who had failed past therapy with regimens containing Peg-IFN (including Peg-IFN plus a protease inhibitor). Patients received SOF/LDV with or without RBV for 12 or 24 weeks.

In ION-3, 647 non-cirrhotic treatment-naïve genotype 1 HCV patients received SOF/LDV with or without RBV for 8 weeks or without RBV for 12 weeks.

The SOF/LDV fixed-dose combination is an investigational product and its safety and efficacy has not yet been established.    

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.    

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that Gilead may be unable to file for U.S. regulatory approval of the SOF/LDV fixed-dose combination in the currently anticipated timelines. In addition, the FDA and other regulatory agencies may not approve the SOF/LDV fixed-dose combination, and any marketing approvals, if granted, may have significant limitations on its use. Additional clinical studies of sofosbuvir and the SOF/LDV fixed-dose combination, including results from the 24-week arms of ION-1, may not produce favorable results. As a result, Gilead may not be able to successfully commercialize the SOF/LDV fixed-dose combination, and may make a strategic decision to discontinue its development if, for example, the market for the product fails to materialize as expected. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2013, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. full prescribing information for Sovaldi is available at

Sovaldi is a trademark of Gilead Sciences, Inc., or its related companies.

For more information on Gilead Sciences, please visit the company’s website at, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

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