RED BANK, N.J., Nov. 22, 2021 /PRNewswire/ -- Provention
Bio, Inc. (Nasdaq: PRVB), a biopharmaceutical company dedicated to
intercepting and preventing immune-mediated disease, today provided
an update on its ongoing efforts to address U.S. Food and Drug
Administration (FDA) considerations cited in the Complete Response
Letter (CRL) issued to the Company by the FDA on July 2, 2021, pertaining to comparability between
the Company's planned teplizumab commercial product and clinical
drug product used in historical trials of teplizumab.
On November 18, 2021, the Company
had a Type A meeting with the FDA to discuss the population
pharmacokinetic (popPK) model to be used for the purpose of planned
commercial and clinical drug product comparison. In preliminary
meeting comments, the FDA approved the Company proceeding to
populate the popPK model with data collected from patients
receiving therapeutic doses of teplizumab in a
pharmacokinetic/pharmacodynamic (PK/PD) substudy of the ongoing
PROTECT Phase 3 trial in newly diagnosed type 1 diabetes (T1D)
patients (Commercial Product N~30 patients, Clinical Drug Product
N~130 patients).
The Company's preliminary analysis from the popPK model produced
the following top-line results:
Geometric mean of the ratio of commercial to clinical drug
product [90% Confidence Interval (CI)]
- 83.2% AUC Infinity [CI: 76.9 – 89.9]
- 85.3% AUC Day 13 [CI: 78.0 – 93.3]
- 86.5% CMAX [CI: 83.9 – 89.3]
These results are not final and are subject to ongoing review of
both the data and the popPK model by the FDA and the Company.
As anticipated, given teplizumab's target mediated mechanism of
clearance, the difference in exposure (AUC Day 13 and 0-infinity)
between commercial product and clinical drug product observed in a
prior single, fractional low dose PK/PD study in healthy volunteers
is greatly reduced when the products are administered and compared
in accordance with the higher therapeutic dosing regimen used in
T1D patients. Along with previously reported physicochemical and
pharmacodynamic data, as well as the immunogenicity and safety
profiles, it is the Company's current opinion that, collectively,
these preliminary results support comparability of the commercial
product and clinical drug product. The FDA, the ultimate decision
maker on the matter, is conducting an independent review of the
data and may have a different opinion. The Company looks forward to
further discussing these results with the FDA to support the FDA's
review.
"We are very pleased that we were able to reach agreement with
the FDA on progressing the popPK model, which enabled us to
generate the comparability results being shared with you today,"
said Ashleigh Palmer, Co-Founder and
CEO of Provention Bio. "We are encouraged by these preliminary
results, which we believe are consistent with our understanding of
the target mediated clearance mechanism of teplizumab and could
potentially explain the differences observed in the previously
reported single, fractional low dose PK/PD study in healthy
volunteers. We look forward to continuing our discussions with the
FDA as they conduct their own review of the data and determining
the next steps in the pathway to the Company's goal of ultimately
providing teplizumab to T1D patients who are at risk of developing
end-stage insulin-dependent disease."
Additionally, at the Type A meeting held on November 18, 2021, the FDA expressed its
concurrence with the Company proceeding to schedule a Type B,
pre-Biologics License Application (BLA) re-submission meeting.
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 Company's
preliminary analysis and ongoing review of the results of the PK/PD
substudy data, the potential for PK/PD substudy data and analyses
to address the FDA's PK comparability considerations, the timing of
the FDA's review of such data and analyses if submitted by the
Company and the Company's plans to address the other matters raised
in the CRL. These statements may be identified by the use of
forward-looking words such as "will," "believe," 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 FDA disagreeing with the Company's interpretation of
data and analysis, including the preliminary PK/PD data referenced
in this release which could change as these data are finalized;
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; any inability to satisfactorily address other
matters cited in the CRL including relating to product quality, the
safety update required by FDA or any other FDA requirements for an
approval of teplizumab; the 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 September 30, 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.