Valeant Pharmaceuticals to Acquire Consensus Interferon (Infergen) from Intermune  

Valeant Pharmaceuticals International announced on November 29 that it has agreed to acquire US and Canadian rights to the hepatitis C drug consensus interferon (aka interferon alfacon-1) [Infergen] from InterMune, Inc. Valeant will pay InterMune $113.5 million in cash upon closing, and subsequent milestone payments of up to approximately $22.5 million. Valeant also will acquire an estimated $6.5 million in inventory from InterMune. Following are excerpts from the Valeant announcement.

 “The acquisition of Infergen will have an immediate sales impact on Valeant and provide us with a valuable addition to one of our core therapeutic areas,” said Timothy C. Tyson, Valeant’s president and chief executive officer. “In addition, we intend to hire up to 50 of InterMune’s sales and marketing force, which will help to provide Valeant with an immediate presence in the hepatitis C market and position us for the anticipated launch of Viramidine.” Viramidine, currently in Phase 3 clinical trials, is expected to be launched in 2007.

Infergen or consensus interferon, is a bio-optimized, selective and highly potent type 1 interferon alpha originally developed by Amgen and launched in the United States in 1997. It is currently indicated as monotherapy for the treatment of adult patients suffering from chronic hepatitis C viral infections with compensated liver disease and is dosed three times per week.

Infergen is the only interferon with data in the label regarding use in patients following relapse or non-response to certain previous treatments. Infergen is being studied in ongoing clinical trials to establish additional labeling for daily use with ribavirin. Enrollment in the Phase 3 IHRC-001 (DIRECT) trial was completed in mid-2005 with 514 patients at 40 sites in the United States.

The DIRECT trial, which should be completed in 2007, is evaluating the safety and efficacy of both 9mcg and 15mcg doses of daily Infergen in combination with ribavirin in non-responders. Management of the DIRECT trial will be transitioned from InterMune to Valeant following the closing of the transaction.

Sales of Infergen were $22 million in 2004. For the first nine months of 2005, sales of Infergen increased by 79 percent to $25.3 million compared to $14.2 million for the first nine months of 2004. The acquisition of Infergen is expected to be neutral in 2005, excluding the impact of acquired in-process research and development, which is estimated to be approximately $45 million, and modestly dilutive in 2006.

According to the Centers for Disease Control and Prevention, an estimated 3.9 million Americans (1.8 percent) have been infected with the hepatitis C virus (HCV). HCV causes an estimated 10,000 to 12,000 deaths annually in the United States and is the leading cause of the need for liver transplants. The prevalence of HCV is increasing and approximately half of all patients with compensated liver disease do not respond to first-line treatment. There are approximately 250,000 of these non-responder patients currently in the U.S. and the number is growing by an estimated 50,000 each year.

About Valeant

Valeant Pharmaceuticals International (NYSE:VRX) is a global, research-based specialty pharmaceutical company that discovers, develops, manufactures and markets products primarily in the areas of neurology, infectious disease and dermatology. More information about Valeant can be found at www.valeant.com

11/30/05

Source
Valeant Pharmaceticals. VALEANT PHARMACEUTICALS AGREES TO ACQUIRE RIGHTS TO HEP-C DRUG INFERGEN® FROM INTERMUNE. Press Release. November 28, 2005.

It is well known that greater than 50% of HCV genotype 1 individuals treated with the standard of care, peginterferon alfa plus ribavirin, fail to achieve a sustained virological response (SVR).

Results of a few studies suggest that consensus interferon (CIFN) (Infergen) in combination with ribavirin (RBV) may be particularly active against HCV genotype 1 and therefore might improve SVR rates in this patient population.

In the current study, researchers at multiple US medical centers sought to evaluate the effects of treatment with  Proof of concept study to compare treatment with CIFN/RBV to pegylated interferon (PEGIFN) and RBV in achieving SVR.

In this prospective, randomized clinical trial, treatment-naïve HCV genotype-1 patients received either CIFN 15 mcg TIW and weight-based generic ribavirin (Ribasphere) (group 1) or PEG-Intron 1.5 mcg/kg/week and weight based ribavirin (Rebetol), (group 2).

Fifty-nine individuals were enrolled, 30 in group 1 and 29 in group 2.

Treatment lasted 48 weeks if HCV RNA was undetectable at week 24, otherwise drugs were discontinued. SVR was determined at week 72.

Safety laboratory tests and adverse events (AE) assessments were performed monthly. To date all subjects have completed week 48 and 56 subjects have finished week 72.

Results

- At baseline the 2 groups were similar in gender (67% men), age (mean = 44 years), weight (202 lbs men, 152 lbs women), ethnicity (59% Caucasian, 30% African American), high viral load (75%, mean levels:  3.8 and 3.6 million IU/mL for groups 1 and 2) and hemoglobin (mean: 15 g/dL).

- Cirrhosis was diagnosed in 3 subjects in group 1 and 5 subjects in group 2. The SVR was similar for both groups: 37% for CIFN/RBV and 35% for PEGIFN/RBV.

- No subject dropped hemoglobin to <8.5 g/dL. Neutrophils dropped to <750/uL in 13% and 24% of groups 1 and 2, respectively (p= 0.29).

- Dose modification for one or two drugs were required in 37% and 62% in each of the 2 groups (p=0.09).

- AE were flu-like symptoms in 100% and 93%, headache in 63% and 39%, fatigue in 77% and 50%, mood disorders in 67% and 66%.

- Serious AE were observed in 6 subjects (3 per group) (cellulitis, severe fatigue, psychosis, seizure, dehydration, EtOH recidivism, and pyelonephritis).

 

Based on these results, the study authors conclude, “CIFN/RBV combination therapy elicited a comparable SVR to PEGIFN/RBV in previously untreated subjects with genotype-1 chronic HCV.”

“There were no relapsers among the CIFN/RBV treated group.”

“The AE profile for CIFN/RBV demonstrated less neutropenia and dose reductions.”

“A larger clinical trial for genotype-1 chronic HCV infection utilizing CIFN and ribavirin is warranted.

11/28/05

Reference
M Sjogren and others. Sustained Virologic Response Rates from a Randomized Trial of HCV Genotype-1 Subjects Treated with Either Consensus IFN and Ribavirin or Pegylated Interferon alfa-2b and Ribavirin. Abstract 851. 56th annual meeting of the American Association for the Study of Liver Diseases. November 11-15, 2005. San Francisco, CA.

Currently, there are no FDA-approved treatment options for individuals who fail to achieve a sustained virological response (SVR) to the standard of care—peginterferon plus ribavirin combination therapy. In the present review, investigators at 3 midwestern medical centers describe their experience using consensus interferon (CIFN) (Infergen) [aka interferon alfacon-1] plus ribavirin (RBV) in nonresponders (NR) to peginterferon + ribavirin

All patients were treated initially with IFN alfa-2a (Pegasys) monotherapy or Peg IFN + RBV. Those who failed to achieve undetectable HCV RNA were classified as NR and were then retreated with CIFN + weight-based RBV (800 mg-1200 mg/day) for at least 48 weeks.

Pretreatment liver biopsy, HCV genotype, viral load and various demographic information were collected for all subjects. Patients on CIFN + RBV retreatment were allowed to use growth factors to continue with their treatment on an as needed basis.

All patients received CIFN at a starting dose of 15 mcg/daily with weight-based RBV. Doses were adjusted as necessary for hematological side effects.

Results

• 79 patients were screened and 76 patients were treated with CIFN and RBV (65% Caucasian, 16% African American, 4% Hispanic, 15% other);
• 49 male and 27 female; age ranged from 20-76 years (Mean: 61 (80%) had HCV genotype 1;
• 36 (47%) had Metavir fibrosis F3/F4.
• At the end of treatment (week 48), 55 (72%) patients were HCV RNA negative.
• At week 72, 38 (50%) achieved an SVR.
• One patient on treatment underwent liver transplantation and stopped treatment. At that time, his viral load had dropped to 1,830 copies/mL. 

Table

Conclusions
According to the authors, “These data suggest that IFN alfacon-1 and weight-based RBV are a potential alternative in Peg IFN plus RBV NR HCV patients. In addition, NR patients with advanced disease (F3/F4) tolerated this therapy well and should be candidates for retreatment with IFN alfacon-1 and RBV.”

“Further study is warranted to confirm these findings.”

11/28/05

Reference
K Chen and others. Consensus interferon and ribavirin in patients with chronic hepatitis C who were nonresponders to prior therapy with either interferon alfa and ribavirin or pegylated interferon and ribavirin. Abstract 1203. 56th annual meeting of the American Association for the Study of Liver Diseases. November 11-15, 2005. San Francisco, CA.

Consensus interferon/CIFN (Infergen) is a synthetic interferon that demonstrates enhanced potency in laboratory studies compared to conventional interferon alfa.

In the present prospective, randomized, multicentre trial, researchers at the Martin-Luther-University Halle-Wittenberg, in Halle, Germany evaluated the efficacy, tolerability and safety of consensus interferon (CIFN) daily versus pegylated IFN a-2b (PEG-IFN) (PegIntron) once weekly in combination with ribavirin (RBV) for HCV non-responders to previous combination treatment with IFN and RBV.

Forty patients with histologically proven chronic hepatitis C, who were HCV RNA positive, had elevated transaminases and previous non-response to treatment with combination therapy with IFN and RBV were randomised to 18 mcg/D CIFN for 6 weeks followed by 9 mcg/D CIFN for 42 weeks (CIFN + RBV: 18 patients) or 1.5 mcg/kg body weight of PEG-Interferon α-2b once a week for 48 weeks (PEG-IFN + RBV: 22 patients), each in combination with RBV (> 10.6 mg/kg body weight daily).

There were no statistical differences between the two groups regarding sex, age, weight, or presence of cirrhosis. All study participants patients had HCV genotype 1b.

Results

Based on an intent-to-treat analysis, the early response rate (ER, 24 weeks of treatment), the end-of-treatment response rate (ETR, 52 weeks of treatment) and the sustained response rate (SR, 6 months after treatment) are reported in Table 1. No significant difference was detected between the two groups.

Table 1: Biochemical and Virological Response

 

• There was no clinically significant difference in the incidence of adverse events between the two groups.
• However, there was a significant higher number of patients withdrawing within the first 6 months from CIFN + RBV than from PEG-IFN because of subjective side-effects (6/18 vs. 1/22, p<0.05, Figure 1).
• In contrast, the treatment was terminated because of primary non-response after 6 months in 8/22 patients treated with PEG-IFN + RBV versus only 2/18 patients treated with CIFN + RBV (p<0.05).

 Figure 1: Patients on treatment

The German authors conclude, “Based on an intent-to-treat analysis, daily CIFN combined with ribavirin has the same antiviral efficacy and safety profile for the treatment of non-responders with chronic hepatitis C as weight adjusted peg-IFNa2b (PegIntron).”

“The daily regimen of CIFN is, however, less well tolerated by patients. A potential higher efficacy can therefore not be established in studies, and will be difficult or impossible to achieve outside of studies.”

11/28/05

Reference
M M Dollinger and others. Efficacy of Daily Consensus Interferon and Ribavirin Compared to PEG-Interferon á-2b and Ribavirin in Non-Responders with chronic Hepatitis C. Abstract 1253. 56th annual meeting of the American Association for the Study of Liver Diseases. November 11-15, 2005. San Francisco, CA