AbbVie to Present Detailed Phase III Results from SAPPHIRE-I and SAPPHIRE-II Studies in Chronic Hepatitis C Patients at the 2014 International Liver Congress(TM)
-SVR(12) rates of 96 percent were achieved in both SAPPHIRE-I (new to therapy) and SAPPHIRE-II (treatment-experienced with pegylated interferon and ribavirin) in adult patients with genotype 1 chronic hepatitis C virus infection
LONDON, April 11, 2014 /PRNewswire/ — AbbVie (NYSE: ABBV) announced that detailed results from its phase III pivotal study, SAPPHIRE-I, will be presented today at the International Liver Congress(TM) (ILC) 2014 and featured in the ILC press conference. Results from the pivotal phase III study, SAPPHIRE-II, were also presented at the congress yesterday. Additionally, results from both SAPPHIRE-I and SAPPHIRE-II have been published online in The New England Journal of Medicine.
In the SAPPHIRE-I (N=631) and SAPPHIRE-II (N=394) placebo-controlled studies, adult, non-cirrhotic patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection receiving the investigational AbbVie regimen with ribavirin (RBV) for 12 weeks achieved sustained virologic response rates 12 weeks post-treatment (SVR(12)) of 96.2 percent (n=455/473) and 96.3 percent (n=286/297), respectively.
In SAPPHIRE-II, treatment-experienced sub-populations randomized to the AbbVie regimen with RBV were prior null responders (49.2 percent), prior relapsers (29.0 percent) and prior partial responders (21.9 percent) to pegylated interferon and RBV.
“Patients with chronic hepatitis C who have not responded well to treatment in the past have historically been more difficult to treat,” said Stefan Zeuzem, M.D., lead clinical investigator on SAPPHIRE-II and Chief of the Department of Medicine at the J.W. Goethe University Hospital in Frankfurt, Germany. “These data show very promising results in people who are infected with either subtype of the GT1 hepatitis C virus and who are either new to therapy or treatment-experienced.”
SAPPHIRE-I and SAPPHIRE-II Results
SAPPHIRE-I SVR12 SAPPHIRE-II SVR12 (n=473) (n=297) ------ ------ All GT1 96.2% (n=455/473) 96.3% (n=286/297)* --- ----------------- ------------------ GT1a 95.3% (n=307/322) 96.0% (n=166/173) ---- ----------------- ----------------- GT1b 98.0% (n=148/151) 96.7% (n=119/123) ---- ----------------- ----------------- Treatment-experienced (GT1a and GT1b) ------------------------------------ Prior null responders n/a 95.2% (n=139/146) ---------- --- ----------------- Prior relapsers n/a 95.3% (n=82/86) --------- --- --------------- Prior partial responders n/a 100.0% (n=65/65) ---------- --- ----------------
*Subgenotype could not be determined for one patient
In SAPPHIRE-I, high response rates were seen across patients with certain variable characteristics, including gender, race, body mass index, fibrosis stage and baseline HCV viral load, as some of these patients have historically had a reduced response to treatment.
“These data provide further evidence that AbbVie’s regimen can achieve high SVR(12) rates across a range of GT1 patients with varying prior treatment experience and response,” said Scott Brun, M.D., Vice President, Pharmaceutical Development, AbbVie. “We are excited to be able to share these results at the ILC and as publications in The New England Journal of Medicine.”
Discontinuations due to adverse events were reported in 0.6 percent of patients in both arms in SAPPHIRE-I and in 1.0 percent of patients receiving the AbbVie regimen in SAPPHIRE-II and no patients receiving placebo. The most commonly reported treatment-emergent adverse events (>10 percent in either arm) for both SAPPHIRE-I and SAPPHIRE-II were fatigue, headache, nausea, asthenia, insomnia, pruritus and diarrhea. Additional common adverse events occurring in the studies were rash in SAPPHIRE-I and dyspnea, cough and myalgia in SAPPHIRE-II. In SAPPHIRE-I, the adverse events that occurred with a significantly greater frequency in the treatment arm compared to placebo were pruritus, insomnia, diarrhea, nausea and asthenia; in SAPPHIRE-II, only pruritus.
About AbbVie’s Investigational HCV Regimen
The AbbVie investigational regimen consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ombitasvir (ABT-267) 25mg, dosed once daily, and dasabuvir (ABT-333) 250mg with or without RBV (weight-based), dosed twice daily. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations.
About Study M11-646 (SAPPHIRE-I)
SAPPHIRE-I is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with AbbVie’s regimen with RBV in non-cirrhotic, GT1a and GT1b HCV-infected adult patients new to therapy.
The study population consisted of 631 patients: 473 were randomized to the AbbVie regimen with RBV for 12 weeks, and 158 patients were randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the AbbVie regimen with RBV for 12 weeks.
Of the 473 patients randomized to the AbbVie regimen with RBV, one case (0.2 percent) of on-treatment virologic failure occurred and seven patients (1.5 percent) experienced post-treatment relapse. In addition, three patients (0.6 percent) were lost to follow-up and seven patients (1.5 percent) discontinued the study prematurely. Patients lost to follow-up were considered treatment failures.
About Study M13-098 (SAPPHIRE-II)
SAPPHIRE-II is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with AbbVie’s regimen with RBV in non-cirrhotic, GT1a and GT1b HCV-infected, treatment-experienced adult patients who previously failed treatment with pegylated interferon and RBV.
The study population consisted of 394 patients: 297 were randomized to the AbbVie regimen with RBV for 12 weeks, and 97 patients were randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the AbbVie regimen with RBV for 12 weeks.
Of the 297 patients randomized to the AbbVie regimen with RBV, there were no cases of on-treatment virologic failure and seven patients (2.4 percent) experienced post-treatment relapse. Of these patients, six were prior null responders and one was a prior relapser. Three patients (1.0 percent) prematurely discontinued therapy due to adverse events and one patient (0.3 percent) prematurely discontinued the study.
Additional information about AbbVie’s phase III studies can be found on www.clinicaltrials.gov.
AbbVie’s HCV Development Program
The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral regimen with and without RBV with the goal of producing high SVR rates in as many patients as possible, including those that typically do not respond well to treatment, such as previous non-responders to interferon-based therapy or patients with advanced liver fibrosis or cirrhosis.
ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie’s other investigational medicines for the treatment of HCV.
Safety Information for Ribavirin and Ritonavir
Ribavirin and ritonavir are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.
There are special safety considerations when prescribing these drugs in approved populations.
Ritonavir must not be used with certain medications due to significant drug-drug interactions and in patients with known hypersensitivity to ritonavir or any of its excipients.
Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus and must not be used alone for this use. Ribavirin causes significant teratogenic effects and must not be used in women who are pregnant or breast-feeding and in men whose female partners are pregnant. Ribavirin must not be used in patients with a history of severe pre-existing cardiac disease, severe hepatic dysfunction or decompensated cirrhosis of the liver, autoimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score > 6.
See approved product labels for more information.
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world’s most complex and serious diseases. AbbVie employs approximately 25,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words “believe,” “expect,” “anticipate,” “project” and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.
Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie’s operations is set forth in Item 1A, “Risk Factors,” in AbbVie’s 2013 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission.
AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.