RED BANK, N.J., July 6, 2021 /PRNewswire/ -- Provention Bio,
Inc. (Nasdaq: PRVB), a biopharmaceutical company dedicated to
intercepting and preventing immune-mediated disease, today
announced that the U.S. Food and Drug Administration (FDA) has
issued a Complete Response Letter (CRL) for the Company's Biologics
License Application (BLA) for teplizumab for the delay of clinical
type 1 diabetes (T1D) in at-risk individuals.
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In the CRL, received late evening on July
2nd, 2021, the FDA stated that a single, low-dose
pharmacokinetic/pharmacodynamic (PK/PD) bridging study in healthy
volunteers to compare planned commercial product with drug product
originating from drug substance manufactured for historic clinical
trials had failed to show PK comparability. "As PK remains the
primary endpoint for demonstration of comparability between the two
products, you will need to establish PK comparability appropriately
between the intended commercial product and the clinical trial
product or provide other data that adequately justify why PK
comparability is not necessary."
The Company expects relevant additional PK/PD data being, or to
be, collected from a PK/PD substudy in patients receiving 12-days
of therapy in the ongoing Phase 3 PROTECT trial in newly diagnosed
T1D patients later this quarter. These data will be analyzed by
independent, unblinded third-parties to maintain the integrity of
this placebo-controlled trial. Upon review of the results from this
substudy, the Company will determine whether to submit these data
to the FDA for its review, along with any other relevant data and
analyses based on our ongoing discussions with FDA, to support PK
comparability or otherwise justify why PK comparability is not
necessary.
In the CRL, the FDA cited several additional considerations
related to product quality, which the Company believes have
either been addressed in amendments already submitted to the BLA or
can be addressed in the short-term. The CRL acknowledged that the
FDA had not reviewed several amendments already submitted by the
Company in response to certain Chemistry, Manufacturing and
Controls (CMC) information requests.
The FDA also stated that certain deficiencies conveyed during a
recent general inspection, not specific to teplizumab, at a
fill/finish manufacturing facility used by the Company will need to
be resolved before approval.
The CRL did not cite any clinical deficiencies related to the
efficacy and safety data packages submitted to the BLA and
confirmed the acceptability of the proposed proprietary name for
teplizumab. The FDA requested that the Company provide a safety
update as part of its BLA resubmission. The CRL contained other
comments and recommendations that do not impact approvability, as
well as general guidance regarding the resubmission process.
"We want to recognize the patients, their families, study
investigators, clinicians and T1D champions that have played such a
crucial role in the development of teplizumab and thank our
partners and our team of dedicated employees and consultants for
their outstanding contributions. We also want to acknowledge the
efforts of Drs. Yanoff and Unger and the review team at the FDA,
who have worked so closely and transparently with us throughout the
priority review of our BLA for this Breakthrough Therapy drug,"
said Ashleigh Palmer, co-founder and
CEO of Provention Bio. "We know the T1D community is urgently
awaiting therapeutic advancements to address their medical needs
and believe our collective passion and committment will continue to
drive us forward to meet this goal. We will continue to work
collaboratively with the FDA to hopefully secure approval of
teplizumab and bring the first disease-modifying therapy for
T1D to at-risk patients as soon as possible."
The Unmet Need in Type 1 Diabetes (T1D):
Over 1.6 million Americans have T1D, an autoimmune disease
caused by the destruction of beta cells. Diagnosis of T1D usually
occurs in children and young adults, but it can happen at any age
after symptoms appear when a person cannot make enough insulin.
However, T1D starts in the body long before any symptoms and can be
detected through a blood test. The psychological impact of T1D is
hard to quantify, but a diagnosis is life-altering, and regular
monitoring and maintenance can be extremely stressful. T1D
typically takes more than a decade off a person's life, and life
expectancy is reduced by 16 years on average for people diagnosed
before the age of 10. Insulin therapy and glucose monitoring are
currently the standard of care for treating clinical-stage T1D, and
are necessary to keep T1D patients alive. The constant monitoring
and administration of insulin represents a significant life-long
burden for patients. No disease-modifying treatments for T1D are
currently available.
About Teplizumab (PRV-031):
Teplizumab is an investigational anti-CD3 monoclonal
antibody (mAb) being developed for the delay of clinical type 1
diabetes (T1D) in at-risk individuals. In the pivotal TN-10 Study,
a single 14-day course of teplizumab delayed insulin-dependent,
clinical-stage disease by a median of at least two years in
presymptomatic patients with Stage 2 T1D compared to placebo. The
observed adverse events were mechanism-based, transient, and
predictable, including lymphopenia, transaminase elevations, rash,
and cytokine release events. These results were published in
the New England Journal of Medicine and simultaneously
presented at the American Diabetes Association meeting in 2019.
More than 800 patients have received teplizumab in multiple
clinical studies involving more than 1,000 subjects. In previous
studies of newly diagnosed patients, teplizumab consistently
demonstrated the ability to preserve beta-cell function as shown by
C-peptide, a measure of endogenous insulin production. It
correspondingly reduced the need for insulin use. Teplizumab has
been granted Breakthrough Therapy Designation by the FDA and PRIME
designation by the European Medicines Administration. Provention is
currently also evaluating teplizumab in patients with newly
diagnosed insulin-dependent T1D (the Phase 3 PROTECT study).
About Provention Bio, Inc.:
Provention Bio, Inc. (Nasdaq: PRVB) is a biopharmaceutical
company focused on advancing the development of investigational
therapies that may intercept and prevent debilitating and
life-threatening immune-mediated disease. The Company's pipeline
includes clinical-stage product candidates that have demonstrated
in pre-clinical or clinical studies proof-of-mechanism and/or
proof-of-concept in autoimmune diseases, including type 1 diabetes,
celiac disease and lupus.
Visit www.ProventionBio.com for more information and follow us
on Twitter: @ProventionBio.
Internet Posting of Information:
Provention Bio, Inc. uses its website, www.proventionbio.com, as
a means of disclosing material nonpublic information and for
complying with its disclosure obligations under Regulation F.D.
Such disclosures will be included on the Company's website in the
"News" section. Accordingly, investors should monitor this portion
of the Company's website, in addition to following its press
releases, SEC filings and public conference calls and webcasts.
Forward-Looking Statements:
Certain statements in this press release are forward-looking,
including but not limited to, statements relating to the medical
need in T1D at-risk patients, the potential therapeutic effects and
safety of teplizumab in at-risk T1D patients, the timing and
ability of the Company to obtain additional PK/PD data from a PK/PD
substudy in the ongoing Phase 3 PROTECT trial and other data and
analysis relevant to PK comparability, the potential for these data
to address the FDA's PK comparability considerations, the Company's
belief that the remaining product quality issues cited in the CRL
are addressed or can be addressed in the short-term, the FDA review
of such data if submitted by the Company, the need for resolution
of deficiencies identified at a fill/finish manufacturer used by
the Company,and the Company's plans to address the other matters
raised in the CRL including plans to continue working
collaboratively with FDA to hopefully secure teplizumab approval .
These statements may be identified by the use of forward-looking
words such as "likely," and "may," among others. These
forward-looking statements are based on the Company's current
expectations and actual results could differ materially. There are
a number of factors that could cause actual events to differ
materially from those indicated by such forward-looking statements.
These factors include, but are not limited to, risks related to
delays in or failure to obtain FDA approvals for teplizumab or
other Company product candidates and the potential for
noncompliance with FDA regulations; any inability to successfully
work with FDA to find a satisfactory solution to address its
concerns in a timely manner or at all, including any inability to
provide the FDA with PK/PD data from our ongoing Phase 3 PROTECT
study or other data sufficient to support an approval of the BLA
for teplizumab; an inability to satisfactorily address other
matters cited in the CRL including relating to product quality,
fill/finish manufacturer deficiencies identified in a general
inspection, safety update required by FDA or any other FDA
requirements for an approval of teplizumabthe potential impacts of
COVID-19 on our business and financial results; changes in law,
regulations, or interpretations and enforcement of regulatory
guidance; uncertainties of patent protection and litigation; the
Company's dependence upon third parties; substantial competition;
the Company's need for additional financing and the risks listed
under "Risk Factors" in the Company's quarterly report on Form 10-Q
for the quarter ended March 31, 2021
and any subsequent filings with the Securities and Exchange
Commission. As with any pharmaceutical under development, there are
significant risks in the development, regulatory approval and
commercialization of new products. Provention does not undertake an
obligation to update or revise any forward-looking statement,
whether as a result of new information, future developments or
otherwise, except as may be required by applicable law. The
information set forth herein speaks only as of the date hereof.
Investor Contacts:
Robert Doody, VP of Investor
Relations
rdoody@proventionbio.com
484-639-7235
Sam Martin, Argot Partners
sam@argotpartners.com
212-600-1902
Media Contact:
Lori Rosen, LDR
Communications
lori@ldrcommunications.com
917-553-6808
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SOURCE Provention Bio, Inc.