FDA Seeking Comments about Expanded Access for Direct-acting Antiviral Drugs for Hepatitis C

		SUMMARY: As a new generation of directly targeted antiviral drugs for hepatitis C virus (HCV) infection approach the final stages of development, the U.S. Food and Drug Administration (FDA) is considering how to provide pre-approval expanded access for people with unmet medical needs, as is done with HIV drugs. The agency is current requesting comments and will hold a public hearing on April 30 near Washington, DC.

By Liz Highleyman

Current standard therapy for chronic hepatitis C is a combination regimen of pegylated interferon (Pegasys or PegIntron) plus ribavirin taken for 24 or 48 weeks (depending on HCV genotype). However, these drugs cause difficult side effects and produce a sustained response, or cure, for only about half of patients with hard-to-treat HCV genotype 1.

Direct-acting antiviral agents (also known as specifically targeted antiviral therapy for hepatitis C, or STAT-C) interfere with specific steps of the viral lifecycle. HCV protease inhibitors, including telaprevir and boceprevir, are furthest along in development, followed by HCV polymerase inhibitors. These agents are expected to be used initially in combination with pegylated interferon plus ribavirin -- hopefully making treatment more effective and potentially shorter -- but pharmaceutical companies are also starting to test all-oral regimens.

Expanded access would allow these drugs to be made available to patients in need of prompt treatment but lacking other options during the late stages of clinical trials or while the FDA is in the process of evaluating a submitted drug for approval.

Below are edited excerpts from 2 recent FDA announcements about the expanded access consideration.

The complete Federal Register Notice may be viewed online.

Expanded Access to Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C Infection in Patients With Unmet Medical Need -- Public Hearing and Request for Comment

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.

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).

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 by contacting the hotel at 301-468-1100 or through the hotel's web page at http://www.rockvillehotel.com.

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 [Ed. Note: Docket No. FDA-2010-N-0107]

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: AccessToDAA@fda.hhs.gov.

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?

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.

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. [Ed. Note: Docket No. FDA-2010-N-0107]

Received comments may be seen in the Division of Dockets Management between 9 am and 4 pm, 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.

Submitting Comments Online

To facilitate submission of electronic comments to please follow these steps.

When you arrive at http://www.regulations.gov, click on the icon labeled "submit a comment" under the "Begin a search" heading. The term "Agency Documents" will automatically appear in the "Select Document Type" window.

Next, enter the term "Direct-Acting Antiviral Agents" in the "Enter Keyword or ID:" window, and press "enter."

Scroll down in the resulting window, where you will see "Public Hearing; Request for Comments: Expanded Access to Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C Infection in Patients With Unmet Medical Need" under "Title."

Click on "Submit a Comment" in the right-hand column, with the heading, "Actions."

Enter the requested information, and your comment in the appropriate windows. The docket number will automatically be included in your comment using this electronic submission method.

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Intron A + Rebetol
Roferon A + Ribavirin

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Experimental Treatments