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
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
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
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
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.
- 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%.
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
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
|
|
Week 48
|
Week 72 (SVR) |
|
HCV RNA negative |
55 (72%) |
38 (50%) |
Conclusions
“Further study is warranted to
confirm these findings.”
11/28/05
Reference
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
|
ER
|
ETR
|
SR
|
|
| CIFN + RBV |
7/18 (39%)
|
7/18 (39%)
|
4/18 (22%)
|
| PEG IFN + RBV |
8/22 (27%)
|
6/22
(27%)
|
5/22 (23%)
|
-
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).
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