Notice2026-11046
Vanda Pharmaceuticals, Inc.; Grant of Hearing Request Regarding a Proposal To Refuse To Approve a Supplemental New Drug Application for HETLIOZ (Tasimelteon)
Primary source
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Published
June 3, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or the Agency) is announcing a formal evidentiary public hearing on the proposal to refuse to approve the supplemental new drug application (sNDA) 205677- 004, submitted by Vanda Pharmaceuticals Inc. (Vanda) for HETLIOZ (tasimelteon) capsules, 20 milligrams (mg), to treat jet lag disorder. On October 11, 2022, the Director of FDA's Center for Drug Evaluation and Research (CDER) published a notice of opportunity for hearing on a proposal to refuse to approve sNDA 205677-004. Vanda submitted a timely request for hearing on that proposal. This notice of hearing provides factual and legal information concerning CDER's proposal to refuse to approve sNDA 205677-004 and identifies the factual issues that will be the subject of the evidentiary hearing.
Full Text
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<title>Federal Register, Volume 91 Issue 106 (Wednesday, June 3, 2026)</title>
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[Federal Register Volume 91, Number 106 (Wednesday, June 3, 2026)]
[Notices]
[Pages 33174-33176]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-11046]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2022-N-2390]
Vanda Pharmaceuticals, Inc.; Grant of Hearing Request Regarding a
Proposal To Refuse To Approve a Supplemental New Drug Application for
HETLIOZ (Tasimelteon)
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA or the Agency) is
announcing a formal evidentiary public hearing on the proposal to
refuse to approve the supplemental new drug application (sNDA) 205677-
004, submitted by Vanda Pharmaceuticals Inc. (Vanda) for HETLIOZ
(tasimelteon) capsules, 20 milligrams (mg), to treat jet lag disorder.
On October 11, 2022, the Director of FDA's Center for Drug Evaluation
and Research (CDER) published a notice of opportunity for hearing on a
proposal to refuse to approve sNDA 205677-004. Vanda submitted a timely
request for hearing on that proposal. This notice of hearing provides
factual and legal information concerning CDER's proposal to refuse to
approve sNDA 205677-004 and identifies the factual issues that will be
the subject of the evidentiary hearing.
DATES: A prehearing conference will be held on July 20, 2026, beginning
at 10 a.m. Eastern Daylight Time. Any person wishing to participate in
this hearing shall submit a written notice of participation by July 6,
2026. Disclosure of data and information as required by 21 CFR 12.85(b)
must be made by August 3, 2026.
ADDRESSES: You may submit a written notice of participation and data
and information required under 21 CFR 12.85 by either of the following
methods:
Electronic Submissions
Submit electronically in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting information. Information
submitted electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a> will be posted to the docket unchanged. Because
your information will be made public, you are solely responsible for
ensuring that your information 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 else's 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 information,
that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> If you want to submit any information with confidential
information that you do not wish to be made available to the public,
submit the information as a written/paper submission and in the manner
detailed (see ``Written/Paper Submission'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
<bullet> Mail/Hand delivery/Courier (for written/paper
submissions): Dockets
[[Page 33175]]
Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
<bullet> For written/paper submissions sent to the Dockets
Management Staff, FDA will post your submission, as well as any
attachments, except for the information submitted, marked and
identified, as confidential, if submitted as detailed in
``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2022-N-2390 for ``Vanda Pharmaceuticals, Inc.; Grant of Hearing
Request Regarding a Proposal to Refuse to Approve a Supplemental New
Drug Application for HETLIOZ (Tasimelteon).'' Received submissions will
be placed in the docket and, except for those submitted as
``Confidential Submissions,'' publicly viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management Staff between 9 a.m.
and 4 p.m., Monday through Friday, 240-402-7500.
<bullet> Confidential Submissions--To make a submission with
confidential information that you do not wish to be made publicly
available, send your submissions 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 CONFIDENTIAL INFORMATION.'' The
Agency will review this copy, including the claimed confidential
information, in its consideration of any decisions on this matter. The
second copy, which will have the claimed confidential information
redacted/blacked out, will be available for public viewing and posted
on <a href="https://www.regulations.gov">https://www.regulations.gov</a>. 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 submissions 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 FDA's posting of information to public dockets, see 80 FR 56469,
September 18, 2015, or access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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, 240-402-7500.
DAB E-File: Beginning on the date of this notice, parties to the
hearing and participants should make submissions related to this
hearing to Departmental Appeals Board electronic filing system (DAB E-
File) at: <a href="https://dab.efile.hhs.gov/">https://dab.efile.hhs.gov/</a>, except insofar as they are
submitting initial notices of participation or disclosing data and
information pursuant to 21 CFR 12.85. Submissions to DAB E-File by
parties and participants must conform to the Case Development Order
(Ref. 1) and other orders issued by the presiding officer. Although
certain regulations in 21 CFR part 12 require submissions for hearing
matters to be filed with the Dockets Management Staff, FDA will deem a
submission made by a party or participant to DAB E-File that conforms
to the presiding officer's orders and this notice to satisfy any such
applicable requirement and will make the submission available on the
docket (see ``Docket''). Non-parties and non-participants should
continue to make submissions through Dockets Management Staff, as
detailed in ``Electronic Submissions'' and ``Written/Paper
Submissions.'' The record will continue to be accessible at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or through the Dockets Management Staff, between 9
a.m. and 4 p.m., Monday through Friday.
FOR FURTHER INFORMATION CONTACT: Karen Fikes, Office of Scientific
Integrity, Food and Drug Administration, 10903 New Hampshire Avenue,
Bldg. 1, Rm. 4218, Silver Spring, MD 20993, 301-796-9603.
SUPPLEMENTARY INFORMATION:
I. Background
On January 31, 2014, FDA approved new drug application 205677 for
HETLIOZ (tasimelteon) for treatment of non-24-hour sleep-wake disorder,
a circadian-rhythm disorder that disproportionately afflicts
individuals who are totally blind. On October 16, 2018, Vanda submitted
sNDA 205677-004, which seeks approval of HETLIOZ (tasimelteon) to treat
jet lag disorder. On August 16, 2019, in accordance with 21 CFR
314.10(a), CDER issued a complete response letter notifying Vanda of
its determination that sNDA 205677-004 is not approvable in its current
form.
On June 30, 2022, Vanda requested an opportunity for a hearing
under 21 CFR 314.110(b)(3) on whether there are grounds under section
505(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21
U.S.C. 355(d)) for denying approval of sNDA 205677-004 for the
treatment of jet lag disorder. On August 29, 2022, by registered mail,
CDER notified Vanda of an opportunity for hearing on a proposal to
refuse to approve sNDA 205677-004. On October 11, 2022, FDA published a
notice of opportunity for hearing on the proposal to refuse approval
(NOOH) in the Federal Register (87 FR 61337). On November 10, 2022,
Vanda filed a notice of participation and requested a hearing and, on
December 12, 2022, submitted information, data, and analyses in support
of that request. On June 12, 2023, CDER submitted a proposed order
denying Vanda's request for a hearing and refusing to approve the sNDA.
On August 11, 2023, Vanda responded to CDER's proposed order. On
September 8, 2023, CDER submitted a reply, which included a revised
proposed order.
After considering the parties' submissions, FDA issued a decision
on March 1, 2024, denying Vanda's request for a hearing and refusing to
approve sNDA 205677-004. The United States Court of Appeals for the
District of Columbia Circuit subsequently set aside FDA's denial of
Vanda's requested hearing and remanded the matter for further
proceedings consistent with its opinion (Vanda Pharms., Inc. v. FDA,
150 F.4th 563 (D.C. Cir. 2025)). At the request of CDER and Vanda,
FDA's Office of the Commissioner later held the matter in abeyance
until February 6, 2026. By letter dated March 2, 2026, the Office of
the Commissioner granted Vanda's hearing request.
II. Presiding Officer
The Office of the Commissioner hereby appoints Administrative Law
Judge Keith W. Sickendick, at the Department of Health and Human
Services' Departmental Appeals Board, to serve as presiding officer
under 21 CFR 12.60 and to conduct the hearing in accordance with
authority prescribed in 21 CFR 12.70.
III. Statutory Grounds for the Hearing
In the NOOH published on October 11, 2022, CDER proposed to refuse
to approve sNDA 205677-004 under section 505(d)(5) of the FD&C Act (21
U.S.C. 355(d)(5)) because the application lacks ``substantial evidence
that the drug will have the effect it purports or is represented to
have under the conditions of use prescribed, recommended, or suggested
in the proposed labeling.''
Vanda has the burden of proof in this proceeding. See 21 CFR
12.87(d) (putting the burden of proof on the
[[Page 33176]]
hearing participant requesting approval of a drug application).
IV. Factual Issues for the Hearing
The central factual issue for the hearing is whether Vanda has
provided substantial evidence that HETLIOZ (tasimelteon) is effective
for treatment of jet lag disorder. As noted by CDER, the decision by
the Court of Appeals for the D.C. Circuit included two key holdings
that limit the factual scope of the hearing with respect to that
central issue. First, the Court upheld FDA's previous conclusion that
the question for any hearing on this matter would be whether there is
substantial evidence of effectiveness for the indication in the sNDA's
proposed labeling--as opposed to any narrower or modified indication
that Vanda might now propose, such as treatment of insomnia related to
jet lag disorder (Vanda, 150 F.4th at 578-79). Second, the Court held
that FDA ``reasonably determined'' that approval of the proposed
indication for HETLIOZ (tasimelteon)--treatment of jet lag disorder--
requires establishing an effect on both sleep and next-day impairment
(Id. at 577 (finding that Vanda has an ``obligation to prove
[effectiveness regarding] the second symptom of jet lag, next-day
impairment'' and that it is not adequate to ``show only that
tasimelteon can remedy sleep-disturbance symptoms'')).
On May 15, 2026, pursuant to 21 CFR 12.85(a)(4), CDER submitted to
the Dockets Management Staff, inter alia, a narrative position
statement that, consistent with the deficiencies listed in the NOOH and
the decision by the Court of Appeals for the D.C. Circuit, identifies
eight specific issues for the hearing:
1. Whether Vanda failed to demonstrate that the primary endpoints in
Studies 2102, 3101, and 3107 were appropriate to assess
effectiveness of tasimelteon for the treatment of jet lag disorder.
2. Whether Vanda failed to demonstrate that the secondary endpoints
in Studies 2102, 3101, and 3107 were appropriate to assess
effectiveness of tasimelteon for the treatment of jet lag disorder.
3. Whether the sNDA provides sufficient evidence of an effect on
symptoms that are integral to jet lag disorder, such that
effectiveness could be established for the proposed indication--
treatment of jet lag disorder.
4. Whether Vanda's analysis of the secondary endpoints in Studies
2102, 3101, and 3107 lacks the statistical rigor to reliably support
conclusions about the effectiveness of tasimelteon for the treatment
of jet lag disorder.
5. Whether the interpretability of Studies 3101 and 3107 is impaired
by the failure to include sufficient data (e.g., via collecting
baseline polysomnograms or other methods) to determine whether
subjects experienced a sleep disturbance after undergoing a phase
advance in the laboratory setting.
6. Whether Vanda failed to provide adequate data to demonstrate
effectiveness of the drug when administered according to the dosing
and administration information in the proposed labeling.
7. Whether Vanda's assessment of next-day functioning was
inadequate.
8. Whether Vanda's application lacks adequate data to characterize
the use of tasimelteon to treat jet lag disorder associated with
westward travel (CDER's Narrative Position Statement, 5-6).
The presiding officer may further revise the factual issues for the
hearing under 21 CFR 12.35(b).
V. Parties to the Hearing
The parties to the hearing will be FDA's CDER and Vanda. Other
interested persons shall be permitted to participate as nonparty
participants as provided by 21 CFR 12.45 and 12.89.
VI. Disclosure of Information by CDER, Vanda, and Other Hearing
Participants
In accordance with 21 CFR 12.85(a), CDER has filed with the Dockets
Management Staff a narrative statement setting forth its position on
the issues of the hearing and a summary of the types of evidence to be
introduced in support of its position in the hearing, together with
copies of data and information contained in the Center's files that
relate to the issues to be resolved at the hearing. Hearing
participants other than CDER, including Vanda, shall disclose data and
information and submit their narrative statements pursuant to 21 CFR
12.85(b) to the Dockets Management Staff (see ADDRESSES) on or before
August 3, 2026, or within another period of time set by the presiding
officer. Interested persons may also examine the data on the drug
subject to this hearing notice (with the exception of any data
identified as confidential pursuant to the provisions of 21 CFR
10.20(j)) via <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management
Staff, between 9 a.m. and 4 p.m., Monday through Friday (see
ADDRESSES).
VII. Prehearing Conference
The prehearing conference will be held on July 20, 2026, beginning
at 10:00 a.m. Eastern Daylight Time, by videoconference with
instructions to be provided. The hearing will be held on a date to be
set at the prehearing conference. Written notices of participation
shall be filed with the Dockets Management Staff no later than July 6,
2026. All participants are required both to attend the prehearing
conference and to be prepared to comply with the provisions of 21 CFR
12.92.
VIII. Conclusion
In accordance with the foregoing, under section 505 the FD&C Act
(21 U.S.C. 355) and under authority delegated to me, I order that a
formal evidentiary public hearing be held on the issues set out in this
notice. The hearing will be open to the public by visiting the HHS Live
Streaming page at <a href="http://www.hhs.gov/live">www.hhs.gov/live</a>. A direct link for the hearing will
be visible on the HHS Live Streaming page once a hearing date has been
set by the presiding officer after the prehearing conference.
Interested persons are encouraged to monitor the docket for any updated
links for public access.
IX. References
1. U.S. Department of Health and Human Services, Departmental Appeals
Board, Civil Remedies Division, Vanda Pharmaceuticals, Inc.
Supplemental New Drug Application for Hetlioz (Tasimelteon), C-26-457,
Case Development Order [Civil Remedies Division Procedures, March 28,
2016], June 3, 2026.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-11046 Filed 6-2-26; 8:45 am]
BILLING CODE 4164-01-P
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</html>Indexed from Federal Register on June 3, 2026.
This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.