[Federal Register Volume 81, Number 74 (Monday, April 18, 2016)]
[Notices]
[Pages 22612-22613]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-08887]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2016-N-1127]
AbbVie Inc. et al; Withdrawal of Approval of Indications Related
to the Coadministration With Statins in Applications for Niacin
Extended-Release Tablets and Fenofibric Acid Delayed-Release Capsules
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is
withdrawing approval of the indications related to the coadministration
with a statin for niacin extended-release (ER) tablets and fenofibric
acid delayed-release (DR) capsules. Affected applications include one
new drug application (NDA) and seven abbreviated new drug applications
(ANDAs) for niacin ER tablets, and one NDA and three ANDAs for
fenofibric acid DR capsules. The holders of these applications have
requested that FDA withdraw approval of the indications and have waived
their opportunities for a hearing.
DATES: The effective date is April 18, 2016.
ADDRESSES: For access to the docket to read background documents, go to
http://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 Division of Dockets Management
(HFA-305), 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Jay Sitlani, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6282, Silver Spring, MD 20993-0002, 301-
796-5202.
SUPPLEMENTARY INFORMATION:
I. Background
A. Applications for Niacin ER Tablets
FDA first approved NDA 020381 for Niaspan (niacin extended-release)
tablets for several indications on July 28, 1997. On March 26, 2009,
FDA approved a revised indication that read as follows:
Niaspan in combination with simvastatin or lovastatin is
indicated for the treatment of primary hyperlipidemia (heterozygous
familial and nonfamilial) and mixed dyslipidemia (Fredrickson Types IIa
and IIb) when treatment with Niaspan, simvastatin, or lovastatin
monotherapy is considered inadequate.
In addition, the following Limitation of Use was added to the
Indications and Usage section of the labeling:
No incremental benefit of Niaspan coadministered with
simvastatin or lovastatin on cardiovascular morbidity and mortality
over and above that demonstrated for niacin, simvastatin, or lovastatin
monotherapy has been established. Niaspan has not been studied in
Fredrickson Type I and III dyslipidemias.
This indication was revised between March 26, 2009, and April 27,
2015, at which time it was removed from the approved labeling. The
Limitation of Use currently reads:
Addition of Niaspan did not reduce cardiovascular
morbidity or mortality among patients treated with simvastatin in a
large, randomized controlled trial (AIM-HIGH).
There are seven approved ANDAs that cited Niaspan as the reference
listed drug (RLD) and that are approved for the same indications as
Niaspan (see table 1).
[[Page 22613]]
Table 1--Affected Niacin Products
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Application No. Drug Application holder
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NDA 020381............................ Niaspan (niacin extended- AbbVie.
release) tablets.
ANDA 076250........................... Niacin extended-release Barr.
tablets.
ANDA 076378........................... Niacin extended-release Barr.
tablets.
ANDA 090446........................... Niacin extended-release Lupin Ltd.
tablets.
ANDA 090860........................... Niacin extended-release Lupin Ltd.
tablets.
ANDA 090892........................... Niacin extended-release Lupin Ltd.
tablets.
ANDA 200484........................... Niacin extended-release Sun Pharma Global.
tablets.
ANDA 201273........................... Niacin extended-release Sun Pharma Global.
tablets.
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B. Applications for Fenofibric Acid DR Capsules
FDA approved NDA 022224 for Trilipix (fenofibric acid) DR capsules
on December 15, 2008, for several indications, including the following:
Trilipix is indicated as an adjunct to diet in combination
with a statin to reduce TG and increase HDL-C in patients with mixed
dyslipidemia and CHD (coronary heart disease) or a CHD risk equivalent
who are on optimal statin therapy to achieve their LDL-C goal.
CHD risk equivalents comprise:
[cir] Other clinical forms of atherosclerotic disease (peripheral
arterial disease, abdominal aortic aneurysm, and symptomatic carotid
artery disease);
[cir] Diabetes; and
[cir] Multiple risk factors that confer a 10-year risk for CHD >20
percent.
The following Limitation of Use was included in the Indications and
Usage section of the labeling:
No incremental benefit of Trilipix on cardiovascular
morbidity and mortality over and above that demonstrated for statin
monotherapy has been established.
Both this indication and the Limitation of Use were removed from
the labeling on April 27, 2015.
There are three approved ANDAs that cited Trilipix as the RLD and
that are approved for the same indications as Trilipix (see table 2).
Table 2--Affected Fenofibric Acid Products
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Application No. Drug Application holder
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NDA 022224............................ Trilipix (fenofibric acid) AbbVie.
delayed-release capsules.
ANDA 201573........................... Fenofibric acid delayed- Anchen Pharmaceuticals.
release capsules.
ANDA 200750........................... Fenofibric acid delayed- Lupin Ltd.
release capsules.
ANDA 200913........................... Fenofibric acid delayed- Mylan Pharmaceuticals Inc.
release capsules.
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II. Withdrawal Under Section 505(e) of the FD&C Act
Based on the collective evidence from several large cardiovascular
outcome trials (Refs. 1-3), the Agency has concluded that the totality
of the scientific evidence no longer supports the conclusion that a
drug-induced reduction in triglyceride levels and/or increase in HDL-
cholesterol levels in statin-treated patients results in a reduction in
the risk of cardiovascular events. Consistent with this conclusion, FDA
has determined that the benefits of niacin ER tablets and fenofibric
acid DR capsules for coadministration with statins no longer outweigh
the risks, and the approvals for this indication should be withdrawn.
FDA requested that the application holders voluntarily discontinue
marketing of niacin ER tablets and fenofibric acid DR capsules for
these indications. The NDA and ANDA holders identified above have
requested in writing that FDA withdraw approval of these indications
and waived their opportunity for a hearing.
Therefore, under section 505(e) of the FD&C Act and under authority
delegated to the Director of the Center for Drug Evaluation and
Research by the Commissioner of Food and Drugs, the approvals of the
indications related to coadministration with statins for the
applications listed in tables 1 and 2 are withdrawn. Introduction or
delivery for introduction of these products with these indications in
interstate commerce without an approved application is illegal and
subject to regulatory action (see sections 505(a) and 301(d) of the
FD&C Act (21 U.S.C. 355(a) and 331(d)).
III. References
The following references are on display in the Division of Dockets
Management (HFA 305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, and are available for viewing by
interested persons between 9 a.m. and 4 p.m., Monday through Friday;
they are also available electronically at http://www.regulations.gov.
FDA has verified the Web site addresses, as of the date this document
publishes in the Federal Register, but Web sites are subject to change
over time.
1. The ACCORD Study Group, ``Effects of Combination Lipid
Therapy in Type 2 Diabetes Mellitus,'' New England Journal of
Medicine, vol. 362, pp. 1563-1574, 2010 (http://www.nejm.org/doi/pdf/10.1056/NEJMoa1001282).
2. The AIM-HIGH Investigators, ``Niacin in Patients with Low HDL
Cholesterol Levels Receiving Intensive Statin Therapy,'' New England
Journal of Medicine, vol. 365, pp. 2255-2267, 2011 (http://www.nejm.org/doi/pdf/10.1056/NEJMoa1107579).
3. The HPS2-THRIVE Collaborative Group, ``Effects of Extended-
Release Niacin with Laropiprant in High-Risk Patients,'' New England
Journal of Medicine, vol. 371(3), pp. 203-212, 2014 (http://www.nejm.org/doi/pdf/10.1056/NEJMoa1300955).
Dated: April 13, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-08887 Filed 4-15-16; 8:45 am]
BILLING CODE 4164-01-P