[Federal Register Volume 86, Number 41 (Thursday, March 4, 2021)]
[Notices]
[Pages 12697-12698]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-04449]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-N-0030]


Determination That BELVIQ (Lorcaserin Hydrochloride) Tablets, 10 
Milligrams, and BELVIQ XR (Lorcaserin Hydrochloride) Extended-Release 
Tablets, 20 Milligrams, Were Withdrawn From Sale for Reasons of Safety 
or Effectiveness

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) has 
determined that BELVIQ (lorcaserin hydrochloride) tablets, 10 
milligrams (mg), and BELVIQ XR (lorcaserin hydrochloride) extended-
release tablets, 20 mg, were withdrawn from sale for reasons of safety 
or effectiveness. The Agency will not accept or approve abbreviated new 
drug applications (ANDAs) for lorcaserin hydrochloride tablets, 10 mg 
and 20 mg.

FOR FURTHER INFORMATION CONTACT: Sungjoon Chi, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6216, Silver Spring, MD 20993-0002, 240-
402-9674, [email protected].

SUPPLEMENTARY INFORMATION: Section 505(j) of the Federal Food, Drug, 
and Cosmetic Act (FD&C Act) (21 U.S.C. 355(j)) allows the submission of 
an ANDA to seek approval to market a generic version of a previously 
approved drug product. In general, to obtain approval, the ANDA 
applicant must show, among other things, that the generic drug product 
has the same active ingredient(s); dosage form; route of 
administration; strength; conditions of use; and, with certain 
exceptions, labeling as the listed drug. In addition, the ANDA 
applicant must show that the generic drug product is bioequivalent to 
the listed drug.
    Section 505(j)(7) of the FD&C Act requires FDA to publish a list of 
all approved drugs. 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 new drug application (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withdrawn from sale for reasons of safety or effectiveness (21 CFR 
314.162).
    A person may petition the Agency to determine, or the Agency may 
determine on its own initiative, whether a listed drug was withdrawn 
from sale for reasons of safety or effectiveness. This determination 
may be made at any time after the drug has been withdrawn from sale, 
but must be made prior to approving an ANDA that refers to the listed 
drug (Sec.  314.161 (21 CFR 314.161)). FDA may not approve an ANDA that 
does not refer to a listed drug.
    BELVIQ (lorcaserin hydrochloride) tablets, 10 mg, is the subject of 
NDA 022529, and BELVIQ XR (lorcaserin hydrochloride) extended-release 
tablets, 20 mg, is the subject of NDA 208524, both held by Eisai Inc. 
(Eisai), and initially approved on June 27, 2012, and July 15, 2016, 
respectively. BELVIQ and BELVIQ XR are indicated as an adjunct to a 
reduced-calorie diet and increased physical activity for chronic weight 
management in adults with an initial body mass index of:
     30 kilograms per square meter (kg/m\2\) or greater 
(obese); or
     27 kg/m\2\ or greater (overweight) in the presence of at 
least one weight-related comorbid condition (e.g., hypertension, 
dyslipidemia, type 2 diabetes).
    After reviewing Agency records and based on the information we have 
at this time, FDA has determined under Sec.  314.161 that BELVIQ 
(lorcaserin hydrochloride) tablets, 10 mg, and BELVIQ XR (lorcaserin 
hydrochloride) extended-release tablets, 20 mg, were withdrawn for 
reasons of safety or effectiveness.
    In 2012, the Agency required the drug manufacturer to conduct a 
randomized, double-blind, placebo-controlled clinical trial to evaluate 
the risk of cardiovascular problems. The Cardiovascular and Metabolic 
Effects of Lorcaserin in Overweight and Obese Patients--Thrombolysis in 
Myocardial Infarction 61 (CAMELLIA-TIMI 61) clinical trial was 
conducted to fulfill this requirement. An analysis of the CAMELLIA-TIMI 
61 trial results suggests an imbalance in cancer in humans. Although 
chance effect cannot be ruled out, the imbalance persisted throughout 
multiple analysis approaches. The clinical findings corroborated by the 
evidence from the animal models informed the Agency's assessment that 
the risk outweighs any potential benefits for the current indications. 
These findings were considered clinically meaningful and could not be 
adequately addressed through labeling. Additional evidence would be 
necessary to investigate this signal; however, the Agency has 
determined that it is unlikely that the necessary safety endpoints 
(i.e., cancer and reproductive safety) can be readily or ethically 
investigated in a clinical trial. Because preclinical or clinical 
studies would first need to be conducted to address these concerns, the 
Agency has determined that this drug product would not be considered 
safe and effective if it were reintroduced to the market.
    FDA issued a Drug Safety Communication on January 14, 2020, 
alerting the public that results from a clinical trial assessing the 
risk of heart-related problems show a possible increased risk of cancer 
with BELVIQ and BELVIQ XR (see https://www.fda.gov/drugs/drug-safety-and-availability/safety-clinical-trial-shows-possible-increased-risk-cancer-weight-loss-medicine-belviq-belviq-xr). On February 13, 2020, 
FDA announced it had asked Eisai to voluntarily withdraw BELVIQ and 
BELVIQ XR from the U.S. market (see https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-withdrawal-weight-loss-drug-belviq-belviq-xr-lorcaserin-market). On February 13, 2020, Eisai 
submitted a request to FDA to withdraw approval of NDA 022529 for 
BELVIQ and NDA 208524 for BELVIQ XR under 21 CFR 314.150(d) and waived 
its opportunity for a hearing. As requested by Eisai, the Agency issued 
a Federal Register notice on September 17, 2020 (85 FR 58063), 
withdrawing approval of the

[[Page 12698]]

applications for BELVIQ (lorcaserin hydrochloride) tablets, 10 mg, and 
BELVIQ XR (lorcaserin hydrochloride) extended-release tablets, 20 mg, 
effective September 17, 2020.
    Accordingly, the Agency will remove BELVIQ (lorcaserin 
hydrochloride) tablets, 10 mg, and BELVIQ XR (lorcaserin hydrochloride) 
extended-release tablets, 20 mg, from the list of drug products 
published in the Orange Book. FDA will not accept or approve ANDAs that 
refer to this drug product.

    Dated: February 26, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-04449 Filed 3-3-21; 8:45 am]
BILLING CODE 4164-01-P