
[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
----------------------------------------------------------------------------------------------------------------
            Application No.                        Drug                          Application holder
----------------------------------------------------------------------------------------------------------------
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.
----------------------------------------------------------------------------------------------------------------

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
----------------------------------------------------------------------------------------------------------------
            Application No.                        Drug                          Application holder
----------------------------------------------------------------------------------------------------------------
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.
----------------------------------------------------------------------------------------------------------------

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


