CLC Comments on FDA Guidance Document on
Expedited Programs for Serious Conditions
(August 26, 2013)
Margaret A.
Hamburg, M.D.
Commissioner
Food and Drug
Administration
10903 New
Hampshire Avenue
Silver Spring,
MD 20993-0002
Filed
electronically at www.regulations.gov
RE:
Docket No.
FDA–2013–D–0575:
Draft Guidance for Industry on Expedited Programs for Serious
Conditions –
Drugs and Biologics
Dear Dr.
Hamburg:
The
undersigned organizations
representing cancer patients, researchers, and physicians and
other health care
professionals appreciate the opportunity to comment on Draft
Guidance for
Industry: Expedited Programs for Serious Conditions – Drugs
and
Biologics. The guidance document provides useful
information to sponsors,
physicians, clinical researchers, and patients regarding four
programs that are
part of the effort to expedite review of drugs for unmet
medical
needs. In this document, the Food and Drug
Administration (FDA) has
preserved “appropriate standards for safety and effectiveness”
while defining
the programs that direct early attention to drugs for serious
conditions.
The
guidance document provides
important advice simply by describing the four programs – fast
track, priority
review, accelerated approval, and breakthrough therapy
designation – in a
single document and explaining the relationships among
them. The guidance
related to three of the programs is largely unchanged, and the
requirements for
requesting breakthrough therapy designation and the benefits
of that
designation are clearly explained.
We offer
comments regarding
several elements of the guidance document. We commend
the agency’s
flexibility in defining when a therapy may meet an unmet
medical need, a status
that potentially allows the drug to qualify for fast track and
accelerated
approval. For example, the agency notes that in
situations where there is
an available therapy for a condition, a new treatment might be
considered to
meet an unmet medical need if it is a targeted cancer therapy
with a novel
mechanism of action that could benefit patients no longer
responding to
available therapy. This is an important clarification
for researchers
seeking to develop new targeted therapies.
The agency
has also offered
useful information about the intermediate clinical endpoint
for accelerated
approval that was included in Food and Drug Administration
Safety and
Innovation Act (FDASIA). The user fee law stated
that accelerated
approval, in addition to being granted on the basis of a
surrogate endpoint
that is reasonably likely to predict clinical benefit, could
be granted on the
basis of a clinical endpoint that 1) can be measured earlier
than irreversible
morbidity or mortality and 2) is reasonably likely to predict
an effect on
irreversible morbidity or mortality or other clinical
benefit. FDA states
that it has limited experience with accelerated approval based
on intermediate
clinical endpoints but offers sponsors advice on the
situations in which such
endpoints would lead to accelerated approval and also
identifies the
possibility these endpoints will support traditional
approval. The
modification of the accelerated approval regulations pursuant
to FDASIA and the
current guidance document combine to clarify the use of the
intermediate
clinical endpoint for accelerated approval.
FDA has
provided clear and
concise guidance to sponsors regarding the application for
breakthrough therapy
designation. The designation requires “preliminary
clinical evidence of a
treatment effect that would represent substantial improvement
over available
therapies for the treatment of a serious condition.” The
preliminary clinical
information must be credible but not definitive at the time of
application. The grant of breakthrough therapy
designation triggers the
engagement of “senior managers and experienced review staff in
a proactive
collaborative, cross-disciplinary review.”
The cancer
community has
already observed the benefits of the breakthrough therapy
designation.
This designation, granted to a number of cancer therapies, has
resulted in the
active engagement of the Office of Hematology and Oncology
Products in the
review process for those products. We note that the
guidance document
urges sponsors with breakthrough therapy designations to be
prepared for
meetings with the agency throughout drug development and to
plan also for a
more rapid pace for other aspects of the drug development
process, including
manufacturing. We trust that sponsors requesting
breakthrough designation
will be prepared to take full advantage of the commitment of
the agency to
speedy development and review.
The
guidance document
identifies circumstances in which a product may lose its
breakthrough therapy
status. If interim data show a substantially smaller
benefit than the
response seen in early clinical testing, a drug may lose its
breakthrough
designation. If breakthrough therapy designation
is granted to two
drugs that are being developed for the same use and one of the
drugs gains
traditional approval, the second drug may lose its
breakthrough status.
The second sponsor could retain its breakthrough status only
if it provided
evidence of substantial improvement over the recently approved
drug. We understand that the approval of the first
drug would mean
that the “unmet need” has been addressed and there is an
available
therapy. However, the possibility of loss of
breakthrough therapy
designation in the middle of drug development creates the sort
of regulatory
uncertainty that sponsors assert undermines the development
process. In
addition, it may be difficult for the second sponsor to
produce evidence of
substantial improvement over a recently approved drug before
completion of its
trial or trials. We urge the agency to reconsider
the policy of
termination of breakthrough status in such
circumstances.
We
appreciate the opportunity
to comment on the draft guidance document and look forward to
working with FDA
in the future to assure the speedy approval of safe and
effective cancer drugs.
Sincerely,
Cancer
Leadership
Council
Bladder Cancer
Advocacy Network
Cancer Support
Community
The Children's Cause
for Cancer Advocacy
Fight Colorectal
Cancer
Hematology/Oncology
Pharmacy Association
International Myeloma
Foundation
Kidney Cancer
Association
The Leukemia &
Lymphoma Society
LIVESTRONG
Foundation
Lymphoma Research
Foundation
National Coalition for
Cancer Survivorship
Ovarian Cancer
National Alliance
Pancreatic Cancer
Action Network
Prevent Cancer
Foundation
Us TOO
International Prostate Cancer Education
and Support Network