BMS urges HCV combo study with Gilead Sciences...

Lovingly pinched from the mighty NATAP.org. BMS calling out Gilead to collaborate at the at the Sanford Bernstein Strategic Decisions Conference in New York, after the success of Gilead's GS-7977 and Bristol's daclatasvir combination in HCV treatment-naive patients presented at EASL. Gilead seems content to use their own, proprietary NS5A inhibitor in combo with GS-7977 thus far, however. 

Bristol urges combo hepatitis C study with Gilead

By Ransdell Pierson

Thu May 31, 2012


(Reuters) - Bristol-Myers Squibb Co renewed calls for biotechnology company Gilead Sciences Inc to test one of its hepatitis C drugs in late-stage trials alongside Bristol's own promising medicine, following impressive results from a mid-stage trial that combined the experimental products.

Bristol's daclatasvir is from a new class of drugs known as NS5A inhibitors. Gilead's GS-7977 is a nucleotide polymerase inhibitor. Both are designed to block enzymes essential to replication of the hepatitis C virus.

Bristol-Myers Chief Executive Lamberto Andreotti, speaking on Thursday at the Sanford Bernstein Strategic Decisions Conference in New York, said patients and both drugmakers stand to benefit if combined Phase III trials of the two medicines are pursued.

"We have a different point of view about whether to enter Phase III (trials) with that combination," Andreotti said. "We believe, for both patients and companies, it is better to move forward" in the short term.

But Andreotti said Gilead instead seemed intent on looking "in-house" -- focusing on combinations of its own products. Gilead officials could not immediately be reached to comment.

Andreotti said there was a "huge, unmet need" for better treatments among an estimated 170 million to 180 million people worldwide believed to be infected with the virus. Transmitted by blood transfusions, sexual contact or shared drug needles, the virus invades the liver and can steadily destroy the organ over decades. It is the most common reason for liver transplants in the United States.

Data from the mid-stage trial combining Gilead's GS-7977 and Bristol's daclatasvir showed a 100 percent response rate in previously untreated patients with the most common form of hepatitis C.

Shares of Gilead jumped 11 percent on April 19 when the data were released, showing the profound benefits of combining its 7977 -- acquired through Gilead's $11 billion purchase of Pharmasset -- with daclatasvir.

At the time, Bristol said Gilead had balked at further collaboration on the combination under study, which was begun while 7977 was owned by Pharmasset.

The results of the mid-stage study were accomplished without interferon, an injected drug that causes flu-like symptoms and other side effects that often lead patients to discontinue or delay treatment. Nor did the study use ribavirin, an older antiviral drug that is also currently part of all treatment regimens.

Instead of working with Bristol-Myers, Gilead is forging ahead with a study of 7977 in combination with its own experimental NS5A inhibitor. In the meantime, Bristol-Myers is testing daclatasvir with a drug similar to 7977 that it acquired with its $2.5 billion purchase of Inhibitex, as well as with other experimental drugs in its development pipeline.

In other remarks at the Sanford Bernstein meeting on Thursday, Andreotti said he expects some form of U.S. healthcare reform to emerge, even if the U.S. Supreme Court rules against extensive reforms approved by Congress and signed into law by President Obama.

The High Court is expected next month to render a decision on the sprawling legislation, which would greatly expand healthcare coverage to uninsured Americans but require bigger fees and rebates from drugmakers and medical device makers.

Andreotti said the enacted reforms "started out on the right foot" but became too complicated for Bristol-Myers and the American people.

The Bristol-Myers CEO said he expects rapidly declining sales of Plavix, a blood-clot preventer which has long been the company's biggest product, due to loss of U.S. patent protection earlier this month and ensuing competition from a number of cheaper generics. The pill, sold in partership with French drugmaker Sanofi, had revenue last year of more than $7 billion -- making it one of the world's top-selling medicines.

Despite expected plunging sales of Plavix, Andreotti said Bristol-Myers has no plans to "downsize" its research spending, having already closed down many company facilities in previous cost-cutting efforts.

Bristol-Myers will adjust future R&D spending in accordance with company performance, and expects significant sales gains to come from Asia but not from Europe, Andreotti said.

He said the company plans over the next few years to concentrate on developing medicines to treat cancer, viral infections and blood clots -- calling those therapeutic areas "the three pillars" of company growth.

(Reporting By Ransdell Pierson; Additional reporting by Bill Berkrot; Editing by Maureen Bavdek and Gunna Dickson)

Boehringer Ingelheim presents interferon-free SOUND-C2 data at EASL...

Today (Saturday, April 21, 2012) is the big day all us HCV drug development nerds (I'd use 'wonks', but that sounds even worse) are waiting for in regards to the late-breaker presentations from EASL and any additional nuggets of info.  One of those presentations will  on the SOUND-C2 trial, featuring the interferon-free combination of Boehringer Ingelheim's HCV PI BI 201335 and polymerase inhibitor BI 207127 both with  ribavirin. According to the press release below, the interim results of the combo show a 68% SVR12 overall in genotype 1 patients in the 28 week arm regardless of IL-28B status. In the 16 week arm, SVR12 was achieved in 59% of patients.  As one might suspect, those subjects that were genotype 1a and non-CC IL-28B status experienced higher relapse and breakthrough rates than those who were G1b and CC.  It was also found that without the benefit of ribavirin, the subjects did substantially worse with only at 39% SVR12.  


Details are still coming, but it appears that this will be a 28 week option and the G1a non-CC patients may either need to go longer (there is a 40 week arm of this study that awaits presentation) or the addition of interferon. Ribavirin will clearly be needed in this combination as well. The odds of dosing confusion are a bit higher, with the PI boasting QD dosing and the polymerase inhibitor BID dosing.


A sub-analysis looking at the efficacy of the combination in the compensated cirrhotic was also presented in poster format. Although the numbers are small and clearly the G1b subjects respond better to the combo, it's encouraging to see any sort of SVR12 in this extremely difficult to treat population, especially without the aid of interferon.

Phase 2b Study of Boehringer Ingelheim’s Interferon-Free Hepatitis C Treatment Shows Undetectable Virus in HCV Genotype-1 Patients 12 Weeks After Treatment Ended (SVR12)

Barcelona, Spain and Ridgefield, CT, April 19, 2012 – New data from a pre-specified interim analysis of the Phase 2b SOUND-C2 study show that 68 percent of genotype-1 (GT1) hepatitis C virus (HCV) patients achieved sustained viral response 12 weeks after the end of treatment (SVR12) with Boehringer Ingelheim’s investigational direct-acting antiviral compounds – the protease inhibitor BI 201335 and polymerase inhibitor BI 207127 – plus ribavirin (RBV), without interferon. SVR12 has been highly correlated with SVR24, which is a recognized indicator of viral cure. These patients received combination therapy with BI 201335 once-daily (QD), BI 207127 twice-daily (BID) and RBV for 28 weeks. The SOUND-C2 study investigated interferon-free treatment in HCV GT1 patients, the most difficult genotype to treat, regardless of IL-28B status. Among study participants, 10 percent had compensated liver cirrhosis.

“Eliminating interferon from HCV treatment is an urgent need,” said Stefan Zeuzem, M.D., Chief of the Department of Medicine and Professor of Medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany, and lead investigator of the study. “The antiviral activity of BI's all oral direct-acting antiviral compounds in the SOUND-C2 study demonstrates the potential for an interferon-free cure for HCV.”

Furthermore, a separate arm of the SOUND-C2 study showed that after 16 weeks of interferon-free treatment, SVR12 was achieved in 59 percent of patients. Investigators presented relapse data broken out by genotype and IL-28B status. The rate of relapse in the treatment arms ranged between 2 and 10 percent for GT1b and GT1a-CC patients. There was a higher rate of relapse in GT1a non-CC patients, with relapse ranging from 0 to 40 percent. The full results from this interim analysis of SOUND-C2 are being presented on Saturday, April 21, at the International Liver Congress, the 47th Annual Meeting of the European Association of the Study of the Liver (EASL 2012) in Barcelona, Spain (Abstract #101). These results supplement the abstract findings highlighted today during an official EASL press conference.

“We are looking forward to the final results from this study, that we hope will be a significant step towards an interferon-free future for patients with HCV,” said Peter Piliero, M.D., Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “We are committed to the millions of people around the world who are chronically infected with HCV. Through our clinical trial program HCVersoTM, we are working with experts worldwide to ask the difficult questions that remain in HCV to find answers to the challenges that these patients face.”

Planning of the interferon-free Phase 3 clinical trial program is underway.

SOUND-C2 Pre-Specified Interim Analysis
In this open-label Phase 2b study, 362 treatment-naïve GT1 HCV patients were randomized into five interferon-free treatment groups, each with 120 mg BI 201335 QD, but with different dosing of BI 207127 and treatment durations. The randomization was stratified by HCV genotype (1a or 1b) and patient IL-28B genotype, with 41 percent of patients being GT1a and 75 percent being IL-28B CT or TT.

Investigators reported breakthrough broken out by genotype and IL-28B status. In GT1b and GT1a-CC patients, breakthrough occurred in 7 percent of patients in Arm A, 11 percent of patients in Arm B, 19 percent of patients in Arm C, 9 percent of patients in Arm D, and 29 percent of patients in Arm E (no RBV arm). In GT1a non-CC patients, breakthrough occurred in 40 percent of patients in Arm A, 50 percent of patients in Arm B, 25 percent of patients in Arm C, 64 percent of patients in Arm D, and 91 percent of patients in Arm E (no RBV arm).

In this study, the most common adverse events (AEs) were skin (photosensitivity, rash), gastrointestinal (GI) disorders (vomiting, diarrhea), and jaundice due to unconjugated hyperbilirubinemia. Treatment discontinuations due to AEs correlated with increased dosing frequency and treatment duration, with discontinuations ranging from 4.9 percent in Arm A (16 weeks) to 24.7 percent in Arm C (40 weeks). In the arm with BID dosing of BI 207127 (Arm D), discontinuations were 7.7 percent. BID dosing of BI 207127 is planned for Phase 3 investigation.