81 FR 22608 - AbbVie Inc.; Withdrawal of Approval of New Drug Applications for ADVICOR and SIMCOR
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 81, Issue 74 (April 18, 2016)
Food and Drug Administration
Federal Register Volume 81, Issue 74 (April 18, 2016)
| Page Range | 22608-22609 | |
| FR Document | 2016-08894 |
[Federal Register Volume 81, Number 74 (Monday, April 18, 2016)] [Notices] [Pages 22608-22609] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2016-08894] ----------------------------------------------------------------------- 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. ----------------------------------------------------------------------- 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 The Agency has also determined that ADVICOR and SIMCOR were withdrawn from sale for reasons of safety and effectiveness, and FDA will not accept or approve abbreviated new drug applications (ANDAs) that reference ADVICOR or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
![22608 Federal Register / Vol. 81, No. 74 / Monday, April 18, 2016 / Notices
associated with both a physical and Topic 2: Patients’ Perspectives on you need special accommodations
psychological burden. Nerve damage Current Approaches to Treatment because of a disability, please contact
can be caused by diseases such as 1. What are you currently doing to Meghana Chalasani (see FOR FURTHER
diabetes, physical injury, or exposure to INFORMATION CONTACT) at least 7 days
help treat your neuropathic pain
drugs or toxins. The pain associated associated with peripheral neuropathy? before the meeting.
with neuropathies of sensory nerves (Examples may include prescription Patients who are interested in
may be characterized as a pins and medicines, over-the-counter products, presenting comments as part of the
needles sensation, as sharp, jabbing, or and other therapies including non-drug initial panel discussions will be asked
burning, or as an exaggeratedly intense therapies). How has your treatment to indicate in their registration which
or distorted pain response to typically regimen changed over time, and why? topic(s) they wish to address. These
nonpainful touch. While there is 2. How well does your current patients also must send to Patient
currently no cure, treatments for the treatment regimen control your Focused@fda.hhs.gov a brief summary
pain associated with peripheral neuropathic pain? of responses to the topic questions by
neuropathy include prescription a. How well have these treatments May 27, 2016. Panelists will be notified
medications and other approaches such worked for you as your condition has of their selection approximately 7 days
as transcutaneous electrical nerve changed over time? before the public meeting. We will try
stimulation, braces, and behavioral b. Would you define your condition to accommodate all patients and patient
therapies. FDA is interested in the today as being well managed? stakeholders who wish to speak, either
perspectives of patients with peripheral 3. What are the most significant through the panel discussion or
neuropathy on specifically: (1) The downsides to your current treatments, audience participation; however, the
impact of neuropathic pain associated and how do they affect your daily life? duration of comments may be limited by
with peripheral neuropathy and (2) (Examples of downsides may include time constraints.
treatment approaches for the bothersome side effects, going to the Docket Comments: Regardless of
neuropathic pain associated with hospital or clinic for treatment, time whether you attend the public meeting,
peripheral neuropathy. devoted to treatment, restrictions on you can submit electronic or written
driving, etc.) responses to the questions pertaining to
The questions that will be asked of topics 1 and 2 to the public docket (see
patients and patient stakeholders at the 4. Assuming there is no complete cure
for your neuropathic pain, what specific ADDRESSES) by August 10, 2016.
meeting are listed in this section, Received comments may be seen in the
organized by topic. For each topic, a things would you look for in an ideal
treatment for your neuropathic pain? Division of Dockets Management
brief initial patient panel discussion between 9 a.m. and 4 p.m., Monday
will begin the dialogue. This will be What would you consider to be a
meaningful improvement in your through Friday, and will be posted to
followed by a facilitated discussion the docket at http://
inviting comments from other patient condition (for example, specific
symptom improvements or functional www.regulations.gov.
and patient stakeholder participants. In Transcripts: As soon as a transcript is
addition to input generated through this improvements) that a treatment could
provide? available, FDA will post it at http://
public meeting, FDA is interested in www.fda.gov/ForIndustry/UserFees/
receiving patient input addressing these 5. If you had the opportunity to
consider participating in a clinical trial PrescriptionDrugUserFee/
questions through written comments, ucm470608.htm.
which can be submitted to the public studying experimental treatments for
docket (see ADDRESSES). neuropathic pain, what things would Dated: April 13, 2016.
you consider when deciding whether or Leslie Kux,
Topic 1: Disease Symptoms and Daily not to participate? (Examples may Associate Commissioner for Policy.
Impacts That Matter Most to Patients include how severe your neuropathic [FR Doc. 2016–08881 Filed 4–15–16; 8:45 am]
pain is, how well current treatments are
1. How would you describe your working for you, your concern about
BILLING CODE 4164–01–P
neuropathic pain associated with risks, etc.)
peripheral neuropathy? What terms
would you use to describe the most B. Meeting Attendance and DEPARTMENT OF HEALTH AND
bothersome aspects of pain? (Examples Participation HUMAN SERVICES
may include stabbing sensations, If you wish to attend this meeting, Food and Drug Administration
electric shocks, burning or tingling, etc.) visit https://peripheralneuropathypfdd.
2. Are there specific activities that are eventbrite.com. Please register by June [Docket No. FDA–2016–N–1097]
important to you but that you cannot do 3, 2016. If you are unable to attend the
AbbVie Inc.; Withdrawal of Approval of
at all or as fully as you would like meeting in person, you can register to
New Drug Applications for ADVICOR
because of your neuropathic pain? view a live Webcast of the meeting. You
and SIMCOR
(Examples of activities may include will be asked to indicate in your
sleeping through the night, daily registration if you plan to attend in AGENCY: Food and Drug Administration,
hygiene, participation in sports or social person or via the Webcast. Seating will HHS.
activities, intimacy with a spouse or be limited, so early registration is ACTION: Notice.
partner, etc.) recommended. Registration is free and
mstockstill on DSK4VPTVN1PROD with NOTICES
3. How do your neuropathic pain and will be on a first-come, first-served SUMMARY: The Food and Drug
its negative impacts affect your daily life basis. However, FDA may limit the Administration (FDA or Agency) is
on the best days? On the worst days? number of participants from each withdrawing approval of the new drug
organization based on space limitations. applications (NDAs) for ADVICOR
4. How has your neuropathic pain Registrants will receive confirmation (niacin extended-release (ER) and
changed over time? once they have been accepted. Onsite lovastatin) tablets and SIMCOR (niacin
5. What worries you most about your registration on the day of the meeting ER and simvastatin) tablets. The holder
condition? will be based on space availability. If of these two applications, AbbVie Inc.,
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![Federal Register / Vol. 81, No. 74 / Monday, April 18, 2016 / Notices 22609
has requested that FDA withdraw strengths of niacin ER and simvastatin, 355(j)(7)). FDA publishes this list as part
approval of the applications and has respectively: (1) 500 mg, 20 mg; (2) 500 of the ‘‘Approved Drug Products With
waived its opportunity for a hearing. mg, 40 mg; (3) 750 mg, 20 mg; (4) 1 g, Therapeutic Equivalence Evaluations,’’
The Agency has also determined that 20 mg; and (5) 1 g, 40 mg. SIMCOR is which is known generally as the
ADVICOR and SIMCOR were approved for the following indications: ‘‘Orange Book.’’ Under FDA regulations,
withdrawn from sale for reasons of • To reduce TC, LDL–C, apolipoprotein drugs are removed from the list if the
safety and effectiveness, and FDA will B, non-HDL–C, triglycerides (TG), or Agency withdraws or suspends
not accept or approve abbreviated new to increase HDL–C in patients with approval of the drug’s NDA or ANDA
drug applications (ANDAs) that primary hypercholesterolemia and for reasons of safety or effectiveness or
reference ADVICOR or SIMCOR. mixed dyslipidemia when treatment if FDA determines that the listed drug
DATES: The effective date is April 18, with simvastatin monotherapy or was withdrawn from sale for reasons of
2016. niacin ER monotherapy is considered safety or effectiveness (21 CFR 314.161
ADDRESSES: For access to the docket to inadequate and 314.162(a)(2)). For the reasons
read background documents, go to • To reduce TG in patients with summarized in this document, the
http://www.regulations.gov and insert hypertriglyceridemia when treatment Agency has determined that ADVICOR
the docket number, found in brackets in with simvastatin monotherapy or and SIMCOR were voluntarily
the heading of this document, into the niacin ER monotherapy is considered
withdrawn from sale for reasons of
‘‘Search’’ box and follow the prompts inadequate
safety or effectiveness. FDA will remove
and/or go to the Division of Dockets The labeling includes the following NDA 021249 for ADVICOR and NDA
Management (HFA–305), 5630 Fishers Limitation of Use in the Indications and 022078 for SIMCOR from the list of
Lane, Rm. 1061, Rockville, MD 20852. Usage section of the labeling:
products published in the Orange Book
FOR FURTHER INFORMATION CONTACT: Jay
• No incremental benefit of SIMCOR
and will not accept or approve ANDAs
Sitlani, Center for Drug Evaluation and on cardiovascular morbidity and
that reference either drug product.
Research, Food and Drug mortality over and above that
Administration, 10903 New Hampshire demonstrated for simvastatin III. References
Ave., Bldg. 51, Rm. 6282, Silver Spring, monotherapy and niacin monotherapy
has been established. The following references are on
MD 20993–0002, 301–796–5202. display in the Division of Dockets
SUPPLEMENTARY INFORMATION: II. Withdrawal Under Section 505(e) of Management (see ADDRESSES), and are
the FD&C Act
I. Background available for viewing by interested
Based on the collective evidence from persons between 9 a.m. and 4 p.m.,
FDA approved NDA 021249 for several large cardiovascular outcome Monday through Friday; they are also
ADVICOR on December 17, 2001. trials (Refs. 1–3.), the Agency has
ADVICOR is a fixed-combination drug available electronically at http://
concluded that the totality of the www.regulations.gov. FDA has verified
product containing niacin ER and scientific evidence no longer supports
lovastatin in tablet form. The drug is the Web site addresses, as of the date
the conclusion that a drug-induced this document publishes in the Federal
approved in four strengths of niacin ER reduction in triglyceride levels and/or
and lovastatin, respectively: (1) 500 Register, but Web sites are subject to
increase in HDL-cholesterol levels in change over time.
milligrams (mg), 20 mg; (2) 750 mg, 20 statin-treated patients results in a
mg; (3) 1 gram (g), 20 mg; and (4) 1 g, reduction in the risk of cardiovascular 1. The ACCORD Study Group, ‘‘Effects of
40 mg. The approved indication reads as events. Consistent with this conclusion, Combination Lipid Therapy in Type 2
follows: FDA has determined that the benefits of Diabetes Mellitus,’’ New England Journal
ADVICOR is indicated for the ADVICOR and SIMCOR no longer of Medicine, vol. 362, pp. 1563–1574,
treatment of primary outweigh the risks, and approval should 2010 (http://www.nejm.org/doi/pdf/
hypercholesterolemia (heterozygous be withdrawn. 10.1056/NEJMoa1001282).
familial and nonfamilial) and mixed FDA requested that AbbVie Inc. 2. The AIM–HIGH Investigators, ‘‘Niacin in
dyslipidemia (Frederickson Types IIa voluntarily discontinue marketing of Patients with Low HDL Cholesterol
and IIb; Table 6) in: ADVICOR and SIMCOR, and AbbVie Levels Receiving Intensive Statin
• Patients treated with lovastatin who Inc. agreed to do so. AbbVie Inc. also Therapy,’’ New England Journal of
require further TG-lowering or HDL- Medicine, vol. 365, pp. 2255–2267, 2011
has requested in writing that FDA
raising who may benefit from having (http://www.nejm.org/doi/pdf/10.1056/
withdraw approval of NDA 021249 and
niacin added to their regimen NEJMoa1107579).
NDA 022078 and waived its opportunity
• Patients treated with niacin who for a hearing.
3. The HPS2–THRIVE Collaborative Group,
require further LDL-lowering who ‘‘Effects of Extended-Release Niacin with
Therefore, under section 505(e) of the
may benefit from having lovastatin Laropiprant in High-Risk Patients,’’ New
FD&C Act and under authority
added to their regimen England Journal of Medicine, vol. 371(3),
delegated to the Director of the Center
pp. 203–212, 2014 (http://www.nejm.org/
The indication was revised for Drug Evaluation and Research by the doi/pdf/10.1056/NEJMoa1300955).
subsequent to the initial approval and Commissioner of Food and Drugs,
currently states that ADVICOR is approval of ADVICOR and SIMCOR is Dated: April 13, 2016.
approved for the treatment of withdrawn. Introduction or delivery for Leslie Kux,
mstockstill on DSK4VPTVN1PROD with NOTICES
hypercholesterolemia when treatment introduction of these products without Associate Commissioner for Policy.
with both Niaspan and lovastatin is an approved application is illegal and [FR Doc. 2016–08894 Filed 4–15–16; 8:45 am]
appropriate. subject to regulatory action (see sections
BILLING CODE 4164–01–P
FDA approved NDA 022078 for 505(a) and 301(d) of the FD&C Act (21
SIMCOR on February 15, 2008. SIMCOR U.S.C. 355(a) and 331(d)).
is a fixed-combination drug product The Agency is required to publish a
containing niacin ER and simvastatin in list of all approved drugs (see section
tablet form. The drug is approved in five 505(j)(7) of the FD&C Act (21 U.S.C.
VerDate Sep<11>2014 17:54 Apr 15, 2016 Jkt 238001 PO 00000 Frm 00043 Fmt 4703 Sfmt 9990 E:\FR\FM\18APN1.SGM 18APN1](https://thefederalregister.org/doc/81_FR_22682/page/2.svg)
Document Created: 2016-04-16 01:45:30
Document Modified: 2016-04-16 01:45:30
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice. | |
| Dates | The effective date is April 18, 2016. | |
| 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. | |
| FR Citation | 81 FR 22608 |
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