Investigational Compound PEG-Interferon Lambda Achieved Higher Response Rates with Fewer Flu-Like and Musculoskeletal Symptoms and Cytopenias Than PEG-Interferon Alfa in Phase…
Investigational Compound PEG-Interferon Lambda Achieved Higher Response Rates with Fewer Flu-Like and Musculoskeletal Symptoms and Cytopenias Than PEG-Interferon Alfa in Phase IIb Study of 526 Treatment-Naive Hepatitis C Patients
Higher virologic response rates achieved at 4 weeks (RVR)[*] and maintained through 12 weeks of treatment (cEVR)[†] across all genotypes studied
Data presented at The International Liver Congress in Berlin
(PRINCETON, N.J., April 2, 2011) – Bristol-Myers Squibb Company (NYSE: BMY) today announced results from the Phase IIb EMERGE clinical trial, in which treatment with the investigational compound PEG-Interferon lambda and ribavirin achieved higher rates of rapid virologic response (RVR) in genotypes 1, 2, 3, and 4, and complete early virologic response (cEVR) in genotypes 1 and 4 than the standard regimen of PEG-Interferon alfa and ribavirin in treatment-naïve patients chronically infected with hepatitis C (HCV). In this study, there were fewer flu-like and musculoskeletal symptoms and cytopenia, as well as fewer interferon and ribavirin dose reductions for anemia in the PEG-Interferon lambda arms up to 12 weeks. Rates of serious adverse events, depression and other common adverse events (incidence ?10%) were similar across treatment arms up to week 12.
The EMERGE study findings were presented in a late-breaker oral session at the International Liver Congress (ILC), the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany.
“There is a significant unmet medical need for more therapies that can benefit more hepatitis C patients. This is especially true for patients with HCV genotypes 1 and 4, who generally have lower response rates to treatment with PEG-Interferon alfa and ribavirin than patients with other genotypes,” said Stefan Zeuzem, MD, chief of the department of medicine and professor of medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany. “The EMERGE study results demonstrate that PEG-Interferon lambda may have the potential to help address this unmet need, and support further studies of this new type of investigational interferon.”
PEG-Interferon lambda is the first investigational type III interferon. Interferon lambda mediates antiviral activity through a receptor that is distinct from that used by interferon alfa and is present on fewer cell types within the tissues of the body. This restricted distribution of the interferon lambda receptor offers the potential for more targeted delivery of interferon therapy.
Viral Response: HCV Genotypes 1 and 4
In this study, HCV genotype 1 and 4 patients treated with PEG-Interferon lambda achieved statistically significant (p<0.05) higher rates of cEVR (primary study endpoint) versus PEG-Interferon alfa at all doses [lambda 240 µg: 56.3% (n=103), lambda 180 µg: 55.9% (n=102), lambda 120 µg: 55.0% (n=100) vs. alfa: 37.9% (n=103)]. These statistically significant (p<0.05) higher viral response rates were seen as early as four weeks of treatment, with greater rates of RVR at the two higher doses of PEG-Interferon lambda (lambda 240 µg: 16.5%, lambda 180 µg: 14.7%, lambda 120µg: 6.0% vs. alfa: 5.8%).
Viral Response: HCV Genotypes 2 and 3
In patients with HCV genotypes 2 and 3, treatment with all doses of PEG-Interferon lambda achieved cEVR rates similar to PEG-Interferon alfa [lambda 240 µg: 83.3% (n=30), lambda 180 µg: 96.6% (n=29), lambda 120 µg: 90% (n=30), and alfa: 86.2%, (n=29)]. Statistically significant (p<0.05) higher rates of RVR were achieved at the two higher doses of PEG-Interferon lambda (lambda 240 µg: 66.7%, lambda 180 µg: 75.9%, lambda 120 µg: 43.3% vs. alfa: 31%).
In this study, rates of adverse events commonly associated with interferon treatment were lower with PEG-Interferon lambda than with PEG-Interferon alfa. These adverse events included flu-like symptoms (lambda 240 µg: 9.7%; lambda 180 µg: 9.9%; lambda 120 µg: 12.5%; alfa: 42.9%), musculoskeletal symptoms (lambda 240 µg: 14.2%; lambda 180 µg: 14.5%; lambda 120 µg: 18.0%; alfa: 46.6%), neutropenia < 750/mm³ (lambda 240 µg: 0.0%; lambda 180 µg: 0.8%; lambda 120 µg: 0.0%; alfa: 15.2%), anemia with hemoglobin < 10 g/dL (lambda 240 µg: 12.9%; lambda 180 µg: 15.4%; lambda 120 µg: 20.5%; alfa: 43.9%.) and thrombocytopenia < 50K/mm³ (lambda 240 µg: 0.0%; lambda 180 µg: 0.0%; lambda 120 µg: 0.0%; alfa: 14.4%).
The proportion of patients that required interferon dose reductions were: lambda 240 µg: 12.7%; lambda 180 µg: 3.8%; lambda 120 µg: 0.8%; alfa: 18.8%, and the proportion of patients that withheld and/or reduced ribavirin were: lambda 240 µg: 11.2%; lambda 180 µg: 4.6%; lambda 120 µg: 10.2%; alfa: 20.3%. The proportion of patients who required ribavirin dose reductions for anemia were: lambda 240 µg: 0.7%; lambda 180 µg: 1.5%; lambda 120 µg: 2.3%; alfa: 12.8%.
Rates of serious adverse events, depression and other common adverse events (?10%) were similar across treatment arms. Higher rates of elevated liver enzymes [AST or ALT >5x the upper limit of normal (ULN)] were seen in the highest-dose PEG-Interferon lambda treatment arm compared with PEG-Interferon alfa (lambda 240 µg: 17.4%; lambda 180 µg: 2.3%; lambda 120 µg: 0.8%; alfa: 7.6%), and direct bilirubin was also elevated (>1.2 mg/dL) in the highest-dose PEG-Interferon lambda treatment arm compared with PEG-Interferon alfa (lambda 240 µg: 7.6%; lambda 180 µg: 3.9%; lambda 120 µg: 0.8%; alfa: 0.8%); all resolved spontaneously without sequelae or following interferon dose modification and/or discontinuation.
About the EMERGE Phase IIb Study
The EMERGE study is a two-part, randomized, controlled, multicenter, phase II study of PEG-Interferon lambda in 526 treatment-naïve patients with chronic hepatitis C genotype 1, 2, 3 or 4. Part one of EMERGE was a Phase IIa study, and results were previously presented at The American Association for the Study of Liver Diseases (AASLD) 2010 Liver Meeting. Part two of EMERGE is an ongoing, blinded Phase IIb study designed to evaluate the safety, efficacy, and pharmacokinetics of PEG-Interferon lambda vs. PEG-Interferon alfa, both in combination with ribavirin. The 526 patients were randomized into four dose groups: PEG-Interferon lambda 240 µg (n=134), PEG-Interferon lambda 180 µg (n=131), PEG-Interferon lambda 120 µg (n=128) and PEG-Interferon alfa 180 µg (n=133).
The study will continue for 48 weeks in genotype 1 and 4 patients and 24 weeks in genotype 2 and 3 patients. The primary endpoint of the study is the proportion of patients who achieve complete early virologic response (cEVR).
About PEG-Interferon lambda
PEG-Interferon lambda is the first investigational type III interferon in Phase IIb development for the treatment of hepatitis C. Native human interferon lambda proteins are generated by the immune system in response to viral infection, and signal through a different receptor than native human interferon alfa proteins. Lambda receptors are present on fewer cell types within the human body than alfa receptors. This restricted distribution of the interferon lambda receptor offers the potential for more targeted delivery of interferon therapy.
About Hepatitis C1
Hepatitis C is a virus that infects the liver and is transmitted through direct contact with blood. An estimated 170 million people worldwide are infected with hepatitis C. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, 20 percent will progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a curable disease.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.
Bristol-Myers Squibb Forward Looking Statement
This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the compound described in this release will move from exploratory development into full product development, that clinical trials of this compound will support a regulatory filing, or that the compound will receive regulatory approval or become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2010, in our Quarterly Reports on Form 10-Q, and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
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1 World Health Organization. Hepatitis C. Available at: http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index1.html. Accessed March 9, 2011.
[*] Rapid virologic response (RVR): undetectable viral load (HCV RNA <25 IU/mL) at week 4 [†] Complete early virologic response (cEVR): undetectable viral load at week 12