Information - Licensing Action
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
Food and Drug Administration
1401 Rockville Pike
Rockville, MD 20852-1448
August 7, 2001
Our STN: BL 103949/5002
Nicholas J. Pelliccione, Ph.D.
2000 Galloping Hill Road
Kenilworth, NJ 07033
Dear Dr. Pelliccione:
Your request to supplement your biologics license application for
Peginterferon alfa-2b (PEG-Intron) to include combination therapy
with Ribavirin, USP (Rebetol), for the treatment of chronic
hepatitis C has been approved.
We acknowledge your agreement to conduct post-marketing studies
in patients with chronic hepatitis C and to provide additional
information as described in your August 7, 2001, letter and as
- To assess the safety and efficacy of alternative dose regimens
of Ribavirin when used in combination therapy with Peginterferon
alfa-2b, by directly comparing the safety and efficacy of a
fixed dose (800mg) of Ribavirin to variable, weight-based doses
of Ribavirin. A 3,000 patient study is underway under ----------
and patient accrual will be completed by December 1, 2001. An
interim (24-week) analysis will be completed by May 1, 2002, and
an interim report will be submitted by July 15, 2002. This study
will be completed by May 1, 2003, and a final report (with
revised labeling if applicable) will be submitted by December 1,
- To assess the safety and efficacy of alternative dose regimens
of Peginterferon alfa-2b when used in combination with Ribavirin
in patients with chronic hepatitis C genotype 1, by directly
comparing 1.0 m g/kg and 1.5mg/kg
doses of Peginterferon alfa-2b. In this study either a fixed
(800 mg) or weight-based dose of Ribavirin will be used.
- If CBER concurs that further analyses of currently available
data from study ---------- show that 24-week virologic
response rates are predictive of sustained response rates, the
dose of Ribavirin to be used in this study will be based on
the interim results of the study described in item 1 above.
The final protocol for this study will be submitted to CBER by
March 30, 2002. Patient accrual will be completed by July 30,
2003, the study will be completed by December 20, 2004, and a
final study report (with revised labeling if applicable)
submitted by May 15, 2005.
- Alternatively, a fixed dose of 800 mg Ribavirin will be used
in this study. The final protocol will be submitted to CBER by
October 30, 2001. Patient accrual will be completed by October
30, 2002, the study will be completed by April 30, 2004, and a
final study report (with revised labeling if applicable) will
be submitted to CBER by November 30, 2004.
- To provide sufficient data to determine whether a 6-month
regimen of Peginterferon alfa-2b in combination with Ribavirin
is a safe and effective alternative to a 12-month regimen in
patients with favorable prognostic factors.
- Schering will evaluate the effect of duration of treatment
in a minimum of 1,000 patients derived from the study
described in item 1 above. If less than 1,000 patients are
available from that study Schering will extend enrollment of
that trial or initiate a new 1,000 patient study. Patient
accrual will be completed by December 1, 2001, the study will
be completed by May 1, 2003, and a final study report (with
revised labeling if applicable) will be submitted to CBER by
December 1, 2003.
- Schering will provide data from the ----------. Patient
accrual will be completed by April 2, 2003, the study
completed by March 3, 2004, and a final study report submitted
to CBER by July 15, 2004.
- To determine the relative bioavailability of Ribavirin
capsules (200 mg X 2) when administered with a high fat meal or
a non-fat meal relative to the fasted state. The final protocol
will be submitted by December 15, 2001. Patient accrual will be
completed by March 1, 2002, the study completed by July 1, 2002,
and the final report submitted by December 20, 2002.
- To provide the final study report for the p53 carcinogenicity
study that is being performed as listed in CDER's approval
letter for NDA 20-903 and per subsequent discussions with the
Division of Antiviral Drug Products. A final report will be
submitted by July 31, 2002.
Pursuant to 21 CFR Part 208, FDA has determined that
Peginterferon alfa-2b alone or in combination with Ribavirin
capsules poses a serious and significant public health concern
requiring the distribution of a Medication Guide. Distribution of a
Medication Guide is necessary for safe and effective use of this
product. FDA has determined that Peginterferon alfa-2b is a product
for which patient labeling could help prevent serious adverse
effects and inform the patient of serious risks relative to benefit
that could affect their decisions to use, or continue to use the
product. See 21 CFR 208.1. FDA hereby approves the Medication Guide
you submitted August 7, 2001. In accordance with 21 CFR 208, you are
responsible for ensuring that this Medication Guide is available for
every patient who is dispensed a prescription for this product. In
addition, you are responsible for ensuring that the label of each
package includes a prominent and conspicuous instruction to
authorized dispensers to provide a Medication Guide to each patient
to whom the drug is dispensed, and states how the Medication Guide
is provided. Please note that the Medication Guide must be printed
in a minimum of 10 point high text, as described in 21 CFR 208.20.
Please submit all final printed labeling at the time of use and
include implementation information on FDA Form 2567. Please provide
a PDF-format electronic copy as well as original paper copies (ten
for circulars and five for other labels). In addition, you may wish
to submit draft copies of the proposed introductory advertising and
promotional labeling with an FDA Form 2567 or Form 2253 to the
Center for Biologics Evaluation and Research, Advertising and
Promotional Labeling Branch, HFM-602, 1401 Rockville Pike,
Rockville, MD 20852-1448. Final printed advertising and promotional
labeling should be submitted at the time of initial dissemination,
accompanied by an FDA Form 2567 or Form 2253.
All promotional claims must be consistent with and not contrary
to approved labeling. No comparative promotional claim or claim of
superiority over other products should be made unless data to
support such claims are submitted to and approved by the Center for
Biologics Evaluation and Research.
This information will be included in your biologics license
--- signature ---
Karen D. Weiss, M.D.
Division of Clinical Trial Design and Analysis
Office of Therapeutics Research and Review
Center for Biologics Evaluation and Research
Last Updated: 8/10/2001
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Date created: September 25, 2003