[Federal Register Volume 81, Number 74 (Monday, April 18, 2016)]
[Notices]
[Pages 22608-22609]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-08894]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-N-1097]


AbbVie Inc.; Withdrawal of Approval of New Drug Applications for 
ADVICOR and SIMCOR

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 new drug applications (NDAs) for ADVICOR 
(niacin extended-release (ER) and lovastatin) tablets and SIMCOR 
(niacin ER and simvastatin) tablets. The holder of these two 
applications, AbbVie Inc.,

[[Page 22609]]

has requested that FDA withdraw approval of the applications and has 
waived its opportunity for a hearing. The Agency has also determined 
that ADVICOR and SIMCOR were withdrawn from sale for reasons of safety 
and effectiveness, and FDA will not accept or approve abbreviated new 
drug applications (ANDAs) that reference ADVICOR or SIMCOR.

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

    FDA approved NDA 021249 for ADVICOR on December 17, 2001. ADVICOR 
is a fixed-combination drug product containing niacin ER and lovastatin 
in tablet form. The drug is approved in four strengths of niacin ER and 
lovastatin, respectively: (1) 500 milligrams (mg), 20 mg; (2) 750 mg, 
20 mg; (3) 1 gram (g), 20 mg; and (4) 1 g, 40 mg. The approved 
indication reads as follows:
    ADVICOR is indicated for the treatment of primary 
hypercholesterolemia (heterozygous familial and nonfamilial) and mixed 
dyslipidemia (Frederickson Types IIa and IIb; Table 6) in:

 Patients treated with lovastatin who require further TG-
lowering or HDL-raising who may benefit from having niacin added to 
their regimen
 Patients treated with niacin who require further LDL-lowering 
who may benefit from having lovastatin added to their regimen

    The indication was revised subsequent to the initial approval and 
currently states that ADVICOR is approved for the treatment of 
hypercholesterolemia when treatment with both Niaspan and lovastatin is 
appropriate.
    FDA approved NDA 022078 for SIMCOR on February 15, 2008. SIMCOR is 
a fixed-combination drug product containing niacin ER and simvastatin 
in tablet form. The drug is approved in five strengths of niacin ER and 
simvastatin, respectively: (1) 500 mg, 20 mg; (2) 500 mg, 40 mg; (3) 
750 mg, 20 mg; (4) 1 g, 20 mg; and (5) 1 g, 40 mg. SIMCOR is approved 
for the following indications:

 To reduce TC, LDL-C, apolipoprotein B, non-HDL-C, 
triglycerides (TG), or to increase HDL-C in patients with primary 
hypercholesterolemia and mixed dyslipidemia when treatment with 
simvastatin monotherapy or niacin ER monotherapy is considered 
inadequate
 To reduce TG in patients with hypertriglyceridemia when 
treatment with simvastatin monotherapy or niacin ER monotherapy is 
considered inadequate

    The labeling includes the following Limitation of Use in the 
Indications and Usage section of the labeling:
     No incremental benefit of SIMCOR on cardiovascular 
morbidity and mortality over and above that demonstrated for 
simvastatin monotherapy and niacin monotherapy has been established.

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 ADVICOR and SIMCOR no longer 
outweigh the risks, and approval should be withdrawn.
    FDA requested that AbbVie Inc. voluntarily discontinue marketing of 
ADVICOR and SIMCOR, and AbbVie Inc. agreed to do so. AbbVie Inc. also 
has requested in writing that FDA withdraw approval of NDA 021249 and 
NDA 022078 and waived its 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, approval of ADVICOR and 
SIMCOR is withdrawn. Introduction or delivery for introduction of these 
products 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)).
    The Agency is required to publish a list of all approved drugs (see 
section 505(j)(7) of the FD&C Act (21 U.S.C. 355(j)(7)). FDA publishes 
this list as part of the ``Approved Drug Products With Therapeutic 
Equivalence Evaluations,'' which is known generally as the ``Orange 
Book.'' Under FDA regulations, drugs are removed from the list if the 
Agency withdraws or suspends approval of the drug's NDA or ANDA for 
reasons of safety or effectiveness or if FDA determines that the listed 
drug was withdrawn from sale for reasons of safety or effectiveness (21 
CFR 314.161 and 314.162(a)(2)). For the reasons summarized in this 
document, the Agency has determined that ADVICOR and SIMCOR were 
voluntarily withdrawn from sale for reasons of safety or effectiveness. 
FDA will remove NDA 021249 for ADVICOR and NDA 022078 for SIMCOR from 
the list of products published in the Orange Book and will not accept 
or approve ANDAs that reference either drug product.

III. References

    The following references are on display in the Division of Dockets 
Management (see ADDRESSES), 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. 2016-08894 Filed 4-15-16; 8:45 am]
 BILLING CODE 4164-01-P