[Federal Register Volume 75, Number 46 (Wednesday, March 10, 2010)]
[Notices]
[Pages 11189-11191]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-5055]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2010-N-0107]
Expanded Access to Direct-Acting Antiviral Agents for the
Treatment of Chronic Hepatitis C Infection in Patients With Unmet
Medical Need; Public Hearing; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of public hearing; request for comments.
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SUMMARY: The Food and Drug Administration (FDA or the agency) is
announcing a public hearing to obtain input on the scope and
implementation of potential expanded access programs with direct-acting
antiviral agents (DAAs) for the treatment of chronic hepatitis C (CHC)
infection in patients with unmet medical need. This public hearing is
being held to obtain comments from the public on eligibility criteria
that should be used for patient enrollment in expanded access protocols
involving DAAs and to elicit suggestions for designs of protocols for
treatment investigational new drug applications (INDs) involving DAAs
and other expanded access protocols. In addition, the agency would like
public input on types of studies that should be conducted to obtain
information on patients with unmet medical need including those with
the greatest risk of progression of liver disease and/or the lowest
predicted virologic response rates.
DATES: The public hearing will be held April 30, 2010, from 9 a.m. to 4
p.m. The meeting may be extended or may end early depending on the
level of public participation. Submit written or electronic requests
for oral presentations and comments by April 8, 2010 (see section III
of this document for details). Written or electronic comments will be
accepted after the hearing until June 25, 2010 (see section V of this
document for details).
ADDRESSES: The public hearing will be held at the Hilton Hotel, 1750
Rockville Pike, Rockville, MD 20852. Additional information on parking
and public transportation may be accessed at http://
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www1.hilton.com/en--US/hi/hotel/IADMRHF-Hilton-Washington-DC-Rockville-
Hotel-Executive-Meeting-Ctr-Maryland/index.do. (FDA has verified the
Web site addresses throughout this document, but FDA is not responsible
for any subsequent changes to the Web sites after this document
publishes in the Federal Register.) Submit written comments to the
Division of Dockets Management (HFA-305), Food and Drug Administration,
5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
Submit electronic comments to http://www.regulations.gov. All
comments should be identified with the docket number found in brackets
in the heading of this document. Transcripts of the hearing will be
available for review at the Division of Dockets Management and on the
Internet at http://www.regulations.gov approximately 45 days after the
hearing (see section VI of this document).
FOR FURTHER INFORMATION CONTACT: Susie Dill, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 51, rm. 6183, Silver Spring, MD 20993-0002, 301-796-3437, FAX:
301-847-8753, e-mail: [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
A. CHC
In the United States, hepatitis C virus infection causes 20 percent
of all cases of acute viral hepatitis and from 70 to 90 percent of all
cases of hepatocellular carcinoma. An estimated 3.2 million Americans
are chronically infected with hepatitis C virus. CHC currently is the
leading cause in the United States for liver transplantation, and
modeling suggests that without effective treatment interventions,
significant increases in CHC-associated liver morbidity and/or
mortality could result.
According to treatment guidelines set forth by the American
Association for the Study of Liver Diseases, the current standard of
care (SOC) for treatment of CHC is a pegylated interferon administered
in combination with ribavirin (See Marc G. Ghany, et al., ``Diagnosis,
Management, and Treatment of Hepatitis C: An Update,'' AASLD Practice
Guidelines, (2009), available at http://www.aasld.org/practiceguidelines/Pages/SortablePracticeGuidelinesAlpha.aspx).
Overall, following SOC treatment, sustained virologic response (SVR)
occurs in about 40 to 45 percent of patients with viral genotype 1,
with lower SVR rates for blacks and human immunodeficiency virus (HIV)
co-infected patients. Pegylated interferons and ribavirin are difficult
to tolerate and can cause significant adverse reactions that limit
treatment in many patients or result in substantial morbidity.
Therefore, new drugs are needed (and many are in development) to
increase SVR rates when added to an SOC, potentially to shorten the
duration of interferon-based regimens, or to replace components of SOC
regimens in patients who cannot tolerate interferons or ribavirin. New
drugs also are needed to construct regimens in patients with
decompensated cirrhosis and in patients undergoing liver transplant.
One option for these patients may be early access to these developing
drug products through the ``expanded access'' regulatory scheme.
B. Authority for Expanded Access
FDA regulations provide for treatment INDs or other access
protocols for patients with serious or immediately life-threatening
illnesses who have unmet medical need. See the Expanded Access to
Investigational Drugs for Treatment Use Final Rule (Expanded Access
Rule) (74 FR 40900, August 13, 2009). Under these regulations, a
treatment IND, which permits patients access to unapproved drug
products under certain circumstances prior to final agency approval, is
possible when the following criteria have been met:
(1) The drug is being investigated in a controlled clinical trial
under an IND designed to support a marketing application for the
expanded access use, or all clinical trials of the drug have been
completed;
(2) The sponsor is actively pursuing marketing approval of the drug
for the expanded access use with due diligence; and
(3) There is sufficient clinical evidence of safety and
effectiveness to support the treatment use (21 CFR 312.320(a)).
Alternatively, individual patient INDs and treatment access
protocols for intermediate-sized populations are sometimes possible
earlier in drug development (21 CFR 312.310) (IND use for treatment of
individual patient by licensed physician)); 21 CFR 312.315 (IND use for
treatment of patient population smaller than that typical of treatment
IND). Proposed use under each of these three options also must meet the
criteria set forth in 21 CFR 312.305 (requirements for all expanded
access uses).
C. Expanded Access in CHC Context
Some patients with CHC who have not responded to approved
treatments and/or who are at substantial risk of liver disease
progression may benefit from access to new therapeutic options before
approval through the Expanded Access Rule. On the other hand, receiving
preapproval treatment access via a treatment protocol may have
potential risks such as adverse reactions or the development of drug or
drug-class resistance.
Historically, early access programs with antiretrovirals for the
treatment of HIV allowed many people to gain access to life-saving
drugs. For some individuals, however, early access to a drug resulted
in what amounted to sequential monotherapy and the emergence of
multidrug resistance. Similar to HIV treatment concerns, drug
resistance and drug-class resistance are concerns for DAAs to treat
CHC. Because treatment of CHC requires multiple agents to achieve
acceptable SVR rates and to reduce the emergence of drug resistance to
single agents or drug classes, treatment INDs that include two or more
investigational agents or that allow for co-enrollment in several
treatment IND programs are options to consider, particularly for
previous null responders or for patients who cannot take interferon-
based regimens. However, the use of multiple agents in the context of a
treatment IND adds to the complexity of the implementation and design
of treatment IND protocols. In light of the foregoing, FDA is
soliciting advice from the public on how treatment access protocols for
hepatitis C DAAs may best be designed.
II. Scope of the Public Hearing
FDA is interested in obtaining public comment on the following
issues related to expanded access of DAAs for the treatment of CHC:
1. What types of patients with CHC are most appropriate for
participation in DAA expanded access for CHC with regard to disease
stage, previous treatment, and other disease characteristics?
2. Under what circumstances and in which populations would early
access to a single DAA be appropriate?
3. Under what circumstances and in which populations would early
access to multiple DAAs be appropriate?
4. How can pharmaceutical companies, government, academia, and
community physicians and activists collaborate to provide for the
treatment use of multiple new agents with the goal of maximizing
response and reducing the emergence of drug or multidrug resistance?
5. What potential adverse reactions should be contemplated in
formulating DAA treatment IND use protocols?
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6. How can pharmaceutical companies, government, academia, and
community physicians and activists collaborate to provide for the
treatment use of multiple new agents with the goal of maximizing
response and reducing adverse reactions?
7. In the course of developing DAAs for marketing, what types of
studies should be conducted to best address unmet medical needs for
patients with CHC including those with the greatest risk of progression
of liver disease and/or the lowest predicted virologic response rates?
Examples of studies that help to support clinical protocols or
treatment use protocols in populations of unmet medical need may
include renal and hepatic impairment studies and drug-drug interaction
studies with antiretrovirals.
III. Attendance and/or Participation in the Public Hearing
The public hearing is free and seating will be on a first-come,
first-served basis. Attendees who do not wish to make an oral
presentation do not need to register.
If you wish to make an oral presentation during the hearing, you
must register by submitting a written or electronic request by close of
business on April 8, 2010, to Susie Dill (see FOR FURTHER INFORMATION
CONTACT). You must provide your name, title, business affiliation (if
applicable), address, telephone and fax numbers, e-mail address, and
type of organization you represent (e.g., industry, consumer
organization). You also should submit a brief summary of the
presentation, including the discussion topic(s) that will be addressed
and the approximate time requested for your presentation. We encourage
individuals and organizations with common interests to consolidate or
coordinate their presentations to allow adequate time for each request
for presentation. Persons registered to make an oral presentation
should check in before the hearing.
Participants should submit a copy of each presentation to Susie
Dill (see FOR FURTHER INFORMATION CONTACT). We will file the hearing
schedule, indicating the order of presentation and the time allotted to
each person, with the Division of Dockets Management (see ADDRESSES).
We will mail, e-mail, or telephone the schedule to each participant
before the hearing. In anticipation of the hearing presentations moving
ahead of schedule, participants are encouraged to arrive early to
ensure their designated order of presentation. Participants who are not
present when called risk forfeiting their scheduled time.
If you need special accommodations due to a disability, please
contact Susie Dill (see FOR FURTHER INFORMATION CONTACT) at least 7
days in advance.
IV. Notice of Hearing Under 21 CFR Part 15
The Commissioner of Food and Drugs is announcing that the public
hearing will be held in accordance with part 15 (21 CFR part 15). The
hearing will be conducted by a presiding officer, who will be
accompanied by FDA senior management from the Office of the
Commissioner and the Center for Drug Evaluation and Research.
Under Sec. 15.30(f), the hearing is informal and the rules of
evidence do not apply. No participant may interrupt the presentation of
another participant. Only the presiding officer and panel members may
question any person during or at the conclusion of each presentation
(21 CFR 15.30(e)). Public hearings under part 15 are subject to FDA's
policy and procedures for electronic media coverage of FDA's public
administrative proceedings (part 10 (21 CFR part 10), subpart C), (21
CFR 10.203(a)). Under Sec. 10.205, representatives of the electronic
media may be permitted, subject to certain limitations, to videotape,
film, or otherwise record FDA's public administrative proceedings,
including presentations by participants. The hearing will be
transcribed as stipulated in Sec. 15.30(b) (see section VI of this
document for more details). To the extent that the conditions for the
hearing as described in this document conflict with any provisions set
out in part 15, this notice acts as a waiver of those provisions as
specified in Sec. 15.30(h).
V. Request for Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments for consideration.
Persons who wish to provide additional materials for consideration
should file these materials with the Division of Dockets Management.
You should annotate and organize your comments to identify the specific
questions identified by the topic to which they refer. Submit a single
copy of electronic comments or two paper copies of any mailed comments,
except that individuals may submit one paper copy. Comments are to be
identified with the docket number found in brackets in the heading of
this document. Received comments may be seen in the Division of Dockets
Management between 9 a.m. and 4 p.m., Monday through Friday.
VI. Transcripts
Please be advised that as soon as a transcript is available, it
will be accessible at http://www.regulations.gov. It may be viewed at
the Division of Dockets Management (see ADDRESSES). A transcript also
will be available in either hardcopy or on CD-ROM, after submission of
a Freedom of Information request. Written requests are to be sent to
the Division of Freedom of Information (HFI-35), Office of Management
Programs, Food and Drug Administration, 5600 Fishers Lane, rm. 6-30,
Rockville, MD 20857.
Dated: March 2, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-5055 Filed 3-9-10; 8:45 am]
BILLING CODE 4160-01-S