- FDA discussed a broader indication of "treatment of recently
acutely suicidal patients" with Bipolar Depression.
-
- This broader indication does not require ketamine as the only
stabilization agent.
- The Company estimates this substantially increases the
addressable acute population for its treatment.
- FDA encouraged NRX to request a Breakthrough Therapy Planning
Meeting for NRX-101.
- FDA suggested the NRX-101 clinical development program be
enlarged to allow for chronic treatment of patients with Bipolar
Depression and intermittent suicidality.
-
- This expanded development program could enable the use of
NRX-101 by a broader segment of the approximately 7 million
individuals in the U.S. with Bipolar Disorder on a long-term
basis.
- The Company is considering expanding its current phase 2
clinical trial to a potential registration study based on the FDA
current guidance using newly released commercial-scale NRX-101
product.
- FDA deemed the Company's remaining nonclinical development plan
to be reasonable and indicated that deferring Pediatric and
Adolescent trials until after drug approval appears
reasonable.
RADNOR,
Pa., Feb. 13, 2023 /PRNewswire/ -- NRx
Pharmaceuticals, Inc. (Nasdaq: NRXP) ("NRx Pharmaceuticals",
the "Company"), a clinical-stage biopharmaceutical company, today
reported the minutes of a Type B meeting with the U.S. Food and
Drug Administration's Division of Psychiatry Products held on
January 11, 2023.
NRx Pharma Announces FDA Guidance from
January 11, 2023, Type B
Meeting
The purpose of the meeting was to discuss requirements for
submission of a New Drug Application for NRX-101. FDA noted in
written correspondence that the Special Protocol Agreement (SPA),
granted in April 2019 remains in
effect. Additionally, the FDA suggested during the meeting that a
broadening of the addressable population of the indication (under
the SPA or otherwise) to patients with Severe Bipolar Depression
and Recent Acute Suicidality regardless of how the initial
stabilization was accomplished could represent a more
straightforward development program. This broader indication would
enable the Company to potentially demonstrate the use of NRX-101 to
maintain stabilization from suicidality in patients stabilized
either with ketamine or with other standard of care therapeutic
approaches. This broader indication is not expected to delay the
acute care trial expected to be completed in 2023. FDA noted that,
should the results of such a study be driven primarily by subjects
stabilized with ketamine, a New Drug Application for ketamine would
also be required.
The FDA further guided the Company to broaden the study of
NRX-101 to include chronic/intermittent treatment of patients with
Bipolar Depression and suicidality. This could enable a pathway for
the use of NRX-101 by a broader segment of the approximately 7
million individuals in the U.S. with Bipolar Disorder on a
long-term basis. A portion of this population is already being
addressed in the Company's ongoing phase 2 trial, which recently
passed its first Data Safety Monitoring Board (DSMB) safety review.
Based on this guidance, the Company is considering expanding its
current phase 2 clinical trial to a potential registration study
now that the manufacture of phase 3/commercial-stage NRX-101 has
been completed. The Company previously announced completion of a
Type C meeting in which FDA agreed to the Company's Chemical
Manufacturing Control and stability program for drug manufacture.
As previously announced, the Company currently expects a DSMB
evaluation of efficacy data from this trial by the end of Q1
2023.
The FDA further advised the Company that as a chronic, or
chronic-intermittent treatment, the safety database requirement
under ICH guidelines for NRX-101 should be 1,500 patients, with at
least 100 treated for 1 year. The Company is evaluating the timing
and cost of expanding clinical access to this larger population. In
addition to its ongoing clinical trials, the Company is considering
augmenting its safety database via an expanded access program,
which is now enabled by the availability of commercial-stage
NRX-101 and is expected under federal law governing Breakthrough
Therapy Designation. The Company will seek cost reimbursement for
operating this Expanded Access Program as permitted under current
FDA regulations.
In related comments, the FDA accepted the Company's rationale
for deferring pediatric and adolescent studies with NRX-101 until
after drug approval and advised the Company to include this
rationale in its regulatory filings. The FDA will consider the
Company's submission of an Advice Request to evaluate waiving or
deferring chronic carcinogenicity testing as a post-approval
commitment. Finally, the FDA's Controlled Substances Staff advised
the Company to closely monitor abuse-related adverse events and
possible cases of abuse during clinical trials.
"We appreciate the FDA's support for the development of a drug
that might offer the first approved medicine to patients with
bipolar depression and acute and subacute levels of suicidality"
said Stephen Willard, Chief
Executive Officer of NRx Pharmaceuticals. "With their guidance, we
aim to expand our development program to address the needs of the
broader population of patients with subacute suicidal ideation,
while continuing to focus on those with bipolar depression with
acute suicidal ideation and behavior as per our Breakthrough
Therapy Designation. We anticipate amending the indication under
our SPA to align with the broader stabilized patient population,
and we will discuss this issue further with the FDA at our
Breakthrough Therapy Planning Meeting. FDA has guided us to a path
that potentially serves a significantly greater proportion of the
approximately 7 million patients in the U.S. who have bipolar
disease, half of whom are reported to attempt suicide at some point
in their lives. Our completion of phase 3 commercial stage drug
supply enables us to embark upon that path without delay."
About NRX-101
Up to 50% of individuals with bipolar disorder attempt suicide
over their lifetime, and estimates indicate that up to 20% may
succumb to suicide. The only FDA-approved treatment for patients
with bipolar depression and acute suicidal ideation & behavior
(ASIB) remains electroconvulsive therapy (ECT). Conventional
antidepressants can increase the risk of suicide in certain
patients; hence their labels contain a warning to that effect.
NRX-101 is a patented, oral, fixed dose combination of
D-cycloserine and lurasidone, neither of which has shown addiction
potential. Based on the results of a Phase 2 proof-of-concept
study, NRX-101 received Breakthrough Therapy Designation from the
FDA for the treatment of severe bipolar depression in patients with
ASIB after initial stabilization with ketamine or other effective
therapy.
NRX-101 is one of the first oral antidepressants currently in
late-stage clinical studies targeting the NMDA-receptor in the
brain, which represents potentially a key new mechanism to treat
depression with and without suicidality, as well as PTSD and other
indications. To date, NRX-101 is the only oral NMDA investigational
medicine focused on bipolar depression in patients with acute and
sub-acute suicidality.
About NRx
Pharmaceuticals
Clinical-stage biopharmaceutical company developing therapeutics
for the treatment of central nervous system disorders, specifically
suicidal depression and post-traumatic stress disorder (PTSD). The
company's lead program NRX-101, an oral, fixed-dose combination of
D-cycloserine and lurasidone, targets the brain's NMDA receptor and
is being investigated in a Phase 3 trial under an FDA Special
Protocol Agreement and Breakthrough Therapy Designation in patients
with bipolar depression and suicidal ideation, an indication for
which the only approved treatment is electroshock therapy. NRx
Pharmaceuticals has also initiated a Phase 2b clinical trial in patients with Sub-Acute
Suicidality, a substantially broader indication. The Breakthrough
Therapy Designation and Special Protocol Agreement were awarded by
the FDA based on the Company's prior STABIL-B trial that
demonstrated substantial improvement over available therapy in
reducing depression and suicidality compared to placebo when
patients were treated with NRX-101 after a single dose of
ketamine.
Cautionary Note Regarding
Forward-Looking Statements
This announcement of NRx Pharmaceuticals, Inc. includes
"forward-looking statements" within the meaning of the "safe
harbor" provisions of the U.S. Private Securities Litigation Reform
Act of 1995, which may include, but are not limited to, statements
regarding our financial outlook, product development, business
prospects, and market and industry trends and conditions, as well
as the Company's strategies, plans, objectives, and goals. These
forward-looking statements are based on current beliefs,
expectations, estimates, forecasts, and projections of, as well as
assumptions made by, and information currently available to, the
Company's management.
The Company assumes no obligation to revise any forward-looking
statement, whether as a result of new information, future events or
otherwise. Accordingly, you should not place reliance on any
forward-looking statement, and all forward-looking statements are
herein qualified by reference to the cautionary statements set
forth above.
CORPORATE CONTACT
Molly Cogan
Sr. Director, Global Communications
mcogan@nrxpharma.com
INVESTOR RELATIONS
Suzanne Messere
Investor
Relations
suzanne.messere@sternir.com
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SOURCE NRx Pharmaceuticals, Inc.