[Federal Register Volume 84, Number 110 (Friday, June 7, 2019)]
[Notices]
[Pages 26685-26687]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-11951]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-D-1516]


Nonalcoholic Steatohepatitis With Compensated Cirrhosis: 
Developing Drugs for Treatment; Draft Guidance for Industry; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled 
``Nonalcoholic Steatohepatitis with

[[Page 26686]]

Compensated Cirrhosis: Developing Drugs for Treatment.'' The purpose of 
this draft guidance is to provide the Agency's current recommendations 
regarding the important components of a drug development program for 
nonalcoholic steatohepatitis (NASH) with compensated cirrhosis. This 
draft guidance focuses on the enrollment criteria, trial design, 
efficacy endpoints, and safety considerations for phase 3 trials.

DATES: Submit either electronic or written comments on the draft 
guidance by August 6, 2019 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance at any time as 
follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2019-D-1516 for ``Nonalcoholic Steatohepatitis with Compensated 
Cirrhosis: Developing Drugs for Treatment.'' Received comments will be 
placed in the docket and, except for those submitted as ``Confidential 
Submissions,'' publicly viewable at https://www.regulations.gov or at 
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through 
Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of the draft guidance to 
the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10001 New Hampshire Ave., 
Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002. Send one 
self-addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Frank A. Anania, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 5387, Silver Spring, MD 20993, 240-402-
9725.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Nonalcoholic Steatohepatitis with Compensated Cirrhosis: 
Developing Drugs for Treatment.''
    This draft guidance focuses on the design of clinical trials to 
study patients who have compensated cirrhosis secondary to NASH. This 
draft guidance is in addition to a draft guidance published in 2018 
which discusses the Agency's thinking for the design of clinical trials 
for patients who have NASH but do not have cirrhosis (see the draft 
guidance for industry entitled ``Noncirrhotic Nonalcoholic 
Steatohepatitis with Liver Fibrosis: Developing Drugs for Treatment'' 
available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm627376.pdf).
    NASH is the hepatic manifestation of insulin resistance syndrome 
and is associated with type 2 diabetes, hypertension, 
hypertriglyceridemia, and obesity, among other diseases. NASH-related 
cirrhosis is becoming a major public health problem and is anticipated 
to be the leading indication for orthotopic liver transplantation 
within a decade.
    This draft guidance applies only to compensated cirrhosis and 
specifically excludes patients with decompensated cirrhosis, i.e. 
patients who have already experienced any of several clinical events 
(e.g., variceal bleeding, ascites, hepatic encephalopathy) that are 
associated with high morbidity and significantly reduce their life 
expectancies. This draft guidance describes the criteria for enrolling 
patients with compensated cirrhosis in clinical trials, including the 
histologic criteria to establish the pathological diagnosis of 
cirrhosis.
    This draft guidance provides recommendations on the selection of 
primary efficacy endpoints in clinical trials intended to study 
pharmacological treatments for compensated NASH

[[Page 26687]]

cirrhosis. Finally, the Agency discusses the rationale for recommending 
that sponsors conduct clinical outcome trials for drugs treating 
compensated NASH cirrhosis. The Agency also provides recommendations to 
help ensure safety in patients with hepatic impairment and strategies 
to deal with drug-induced liver injury during a compensated NASH 
cirrhosis clinical trial.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the current thinking of FDA on ``Nonalcoholic 
Steatohepatitis with Compensated Cirrhosis: Developing Drugs for 
Treatment.'' It does not establish any rights for any person and is not 
binding on FDA or the public. You can use an alternative approach if it 
satisfies the requirements of the applicable statutes and regulations. 
This guidance is not subject to Executive Order 12866.

II. Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The 
collections of information under 21 CFR part 312 (Investigational New 
Drug Application) have been approved under OMB control number 0910-
0014. The collections of information in 21 CFR parts 50 and 56 
(Protection of Human Subjects: Documentation of Informed Consent; 
Institutional Review Boards) have been approved under OMB control 
number 0910-0755. The collection of information under 21 CFR part 314, 
including the submission of information under subpart H (``Accelerated 
Approval of New Drugs for Serious or Life-Threatening Illnesses''), has 
been approved under OMB control number 0910-0001. The collection of 
information under the guidance for industry entitled ``Expedited 
Programs for Serious Conditions--Drugs and Biologics'' (available at 
https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm358301.pdf) has been approved under OMB control 
number 0910-0765.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or 
https://www.regulations.gov.

    Dated: June 3, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-11951 Filed 6-6-19; 8:45 am]
 BILLING CODE 4164-01-P


