Agios Establishes Proof-of-Concept for Mitapivat in Non-transfusion-dependent Thalassemia Based on Preliminary Phase 2 Result...
December 08 2019 - 9:00AM
Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of
cellular metabolism to treat cancer and rare genetic diseases,
today announced that clinical proof-of-concept has been established
based on a preliminary analysis of the Phase 2 trial of mitapivat
(AG-348) in patients with non-transfusion-dependent thalassemia.
Mitapivat is an investigational, first-in-class, oral, small
molecule allosteric activator of wild-type and a variety of mutated
pyruvate kinase-R (PKR) enzymes.
The Phase 2 study has enrolled 12 of the intended 17 patients
(nine with β-thalassemia and three with α-thalassemia). As of the
November 14, 2019 data cutoff date, eight patients, all with
β-thalassemia, were evaluable for the primary endpoint of a
hemoglobin increase of ≥1.0 g/dL from baseline in at least one
assessment during Weeks 4-12. All eight patients were treated with
50 mg of mitapivat twice daily for the first six weeks and
escalated to 100 mg twice daily, and all patients remain on
treatment (range 12.4-34.3 weeks). Seven of eight efficacy
evaluable patients achieved a hemoglobin increase of ≥1.0 g/dL, and
for responders the mean hemoglobin increase from baseline was 1.76
g/dL (range, 0.9–3.3 g/dL) during Weeks 4-12. The majority of
adverse events were Grade 1 or 2 and consistent with previously
published Phase 2 data for mitapivat in patients with pyruvate
kinase (PK) deficiency. Updated results from the Phase 2
thalassemia study will be presented at a medical meeting in the
first half of 2020.
“These data demonstrate proof of concept that activation of
wild-type PKR has the potential to convey clinical benefit in
thalassemia and provides compelling evidence to broaden mitapivat
clinical development in this disease,” said Chris Bowden, M.D.,
chief medical officer at Agios. “The safety and tolerability
profile observed in this trial and in adults with pyruvate kinase
deficiency supports the continued investigation of mitapivat
treatment across severe, lifelong hemolytic anemias such as
pyruvate kinase deficiency, thalassemia and sickle cell
disease.”
Mitapivat Phase 2 Trial in Thalassemia The
ongoing Phase 2 study is evaluating the efficacy, safety,
pharmacokinetics and pharmacodynamics of treatment with mitapivat
in adults with non-transfusion-dependent β- and α-thalassemia
(NTDT). This study includes a 24-week core period followed by a
2-year extension period for eligible participants. The primary
endpoint is hemoglobin response. Approximately 17 participants with
NTDT who have a baseline hemoglobin concentration of ≤10 g/dL will
be enrolled. The initial dose of mitapivat is 50 mg twice daily
with one potential dose-level increase to 100 mg twice daily, at
the week six visit based on the participant's safety and hemoglobin
(Hb) concentrations. With a total of 17 patients enrolled, the
study would have 80% power to reject a ≤30% response rate at a
one-sided 0.05 type 1 error rate.
Mitapivat Clinical DevelopmentAgios has two
ongoing global, pivotal trials in adults with PK deficiency that
are on track to complete enrollment by year-end 2019. Learn more at
activatetrials.com.
- ACTIVATE: A placebo-controlled trial with a 1:1 randomization,
expected to enroll approximately 80 patients who do not receive
regular transfusions. The primary endpoint of the trial is the
proportion of patients who achieve a sustained hemoglobin increase
of ≥1.5 g/dL.
- ACTIVATE-T: A single arm trial of up to 40 regularly transfused
patients with a primary endpoint of reduction in transfusion burden
over six months compared to individual historical transfusion
burden over prior 12 months.
In addition to the thalassemia Phase 2 study, mitapivat is being
studied in sickle cell disease under a Cooperative Research and
Development Agreement (CRADA) with the U.S. National Institutes of
Health.
Mitapivat is not approved for use by any regulatory
authority.
Investor Event and Webcast InformationAgios
will host an investor event on Monday, December 9, 2019 at 8:00
p.m. ET in Orlando, Fla. The event will be webcast live and can be
accessed under "Events & Presentations" in the Investors
section of the company's website at www.agios.com. The archived
webcast will be available on the company's website beginning
approximately two hours after the event.
About AgiosAgios is focused on discovering and
developing novel investigational medicines to treat cancer and rare
genetic diseases through scientific leadership in the field of
cellular metabolism. In addition to an active research and
discovery pipeline across both therapeutic areas, Agios has two
approved oncology precision medicines and multiple first-in-class
investigational therapies in clinical and/or preclinical
development. All Agios programs focus on genetically identified
patient populations, leveraging our knowledge of metabolism,
biology and genomics. For more information, please visit the
company's website at www.agios.com.
Cautionary Note Regarding Forward-Looking
Statements This press release contains forward-looking
statements within the meaning of The Private Securities Litigation
Reform Act of 1995. Such forward-looking statements include those
regarding: the potential benefits of mitapivat; Agios’ plans for
the further clinical development of mitapivat and Agios’ strategic
plans and prospects. The words “anticipate,” “believe,” “estimate,”
“expect,” “intend,” “may,” “plan,” “predict,” “project,” “would,”
“could,” “potential,” “possible,” “hope” and similar expressions
are intended to identify forward-looking statements, although not
all forward-looking statements contain these identifying words.
Such statements are subject to numerous important factors, risks
and uncertainties that may cause actual events or results to differ
materially from Agios' current expectations and beliefs. For
example, there can be no guarantee that any product candidate Agios
is developing will successfully commence or complete necessary
preclinical and clinical development phases; that positive safety
and efficacy findings observed in early stage clinical trials will
be replicated in later stage trials; or that development of any of
Agios' product candidates will successfully continue. There can be
no guarantee that any positive developments in Agios' business will
result in stock price appreciation. Management's expectations and,
therefore, any forward-looking statements in this press release
could also be affected by risks and uncertainties relating to a
number of other important factors, including: Agios' results of
clinical trials and preclinical studies, including subsequent
analysis of existing data and new data received from ongoing and
future studies; the content and timing of decisions made by the
U.S. FDA and other regulatory authorities,
investigational review boards at clinical trial sites and
publication review bodies; Agios' ability to obtain and maintain
requisite regulatory approvals and to enroll patients in its
planned clinical trials; unplanned cash requirements and
expenditures; competitive factors; Agios' ability to obtain,
maintain and enforce patent and other intellectual property
protection for any product candidates it is developing; Agios'
ability to maintain key collaborations; and general economic and
market conditions. These and other risks are described in greater
detail under the caption “Risk Factors” included in Agios’ public
filings with the Securities and Exchange Commission. Any
forward-looking statements contained in this press release speak
only as of the date hereof, and Agios expressly disclaims any
obligation to update any forward-looking statements, whether as a
result of new information, future events or otherwise.
Investor & Media Contact: Holly Manning,
617-844-6630 Associate Director, Investor Relations
Holly.Manning@agios.com
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