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Federal Register / Vol. 86, No. 168 / Thursday, September 2, 2021 / Notices
lotter on DSK11XQN23PROD with NOTICES1

Federal eRulemaking Portal:
https www.regulations.gov. Follow the instructions for submitting comments.
Comments submitted electronically, including attachments, to https
www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone elses Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https www.regulations.gov.
If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed see Written/Paper Submissions and Instructions.
Written/Paper Submissions Submit written/paper submissions as follows:
Mail/Hand delivery/Courier for written/paper submissions: Dockets Management Staff HFA305, Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in Instructions.
Instructions: All submissions received must include the Docket No. FDA
2021N0874 for Proposal To Refuse To Approve a New Drug Application for ITCA 650 Exenatide in DUROS Device;
Opportunity for a Hearing. Received comments, those filed in a timely manner see ADDRESSES, will be placed in the docket and, except for those submitted as Confidential Submissions, publicly viewable at https www.regulations.gov or at the Dockets Management Staff between 9
a.m. and 4 p.m., Monday through Friday, 2404027500.
Confidential SubmissionsTo submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states THIS DOCUMENT CONTAINS

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CONFIDENTIAL INFORMATION. The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as confidential. Any information marked as confidential will not be disclosed except in accordance with 21 CFR 10.20
and other applicable disclosure law. For more information about FDAs posting of comments to public dockets, see 80
FR 56469, September 18, 2015, or access the information at: https
www.govinfo.gov/content/pkg/FR-201509-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https
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 Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 2404027500.
FOR FURTHER INFORMATION CONTACT:
Kevin Fain, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 6419, Silver Spring, MD 20993, 3017965842, Kevin.Fain@
fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Proposal To Refuse To Approve NDA
209053
Intarcia submitted NDA 209053 for ITCA 650 exenatide in DUROS device, a drug-device combination product intended to deliver the active ingredient exenatide, a GLP1 receptor agonist RA, on November 21, 2016, under section 505b1 of the Federal Food, Drug, and Cosmetic Act FD&C Act 21
U.S.C. 355b1. Intarcia proposed that ITCA 650 be indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus T2DM.
On September 21, 2017, the former Division of Metabolism and Endocrinology Products DMEP, Office of Drug Evaluation II now the Division of Diabetes, Lipid Disorders, and Obesity, within the Office of Cardiology, Hematology, Endocrinology and
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Nephrology OCHEN in the Office of New Drugs OND in FDAs Center for Drug Evaluation and Research CDER, issued a complete response letter to Intarcia under 314.110a 21 CFR
314.110a stating that NDA 209053
could not be approved in its present form, describing the specific deficiencies and, where possible, recommending ways that Intarcia might remedy these deficiencies. On September 9, 2019, Intarcia resubmitted the NDA under section 505b1 of the FD&C Act. On March 9, 2020, the former DMEP issued a second complete response letter stating that NDA 209053
could not be approved in its present form, describing the specific deficiencies and, where possible, recommending ways that Intarcia might remedy these deficiencies. These deficiencies, which are summarized below, include the following:
1. The clinical trial data demonstrated that ITCA 650 causes acute kidney injury AKI.
a. A signal of AKI was evident in the pivotal phase 3 trials of the ITCA 650
clinical development program. A
standardized Medical Dictionary for Regulatory Activities query for acute renal failure identified reports of AKI
serious adverse events in 14 subjects 0.6 percent who received ITCA 650
versus 4 subjects 0.2 percent who received placebo.
b. The magnitude of the AKI risk was greater for ITCA 650 than for the marketed exenatide products or for other members of the GLP1 RA class.
Although other drugs in the GLP1 RA
class have a risk of AKI, this information is based on spontaneous postmarketing adverse event reports.
The risk of AKI was not detected in the clinical trials that supported the approval of these drugs. In contrast, the risk of AKI was clearly identified in the ITCA 650 clinical trial data. This AKI
risk for ITCA 650, compared to other members of the GLP1 RA class, is particularly concerning because it was identified from these adequate and wellcontrolled clinical trials, which constitute stronger evidence for assessing a drugs safety than spontaneous postmarketing adverse event reports.
c. AKI events experienced by participants who received ITCA 650
sometimes resulted in prolonged hospitalization; complications observed in association with AKI events included dialysis and death.
d. A majority of the serious AKI
events in participants randomized to ITCA 650 appeared to be associated with vomiting, diarrhea, and dehydration, which are known adverse
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