Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field
of cellular metabolism to treat genetically defined diseases, today
announced positive results from its Phase 2, open-label,
multicenter study of mitapivat in adults with non-transfusion
dependent α- or β-thalassemia. Data from the study will be featured
in an oral presentation on Tuesday, June 15, at the European
Hematology Association (EHA) Virtual Congress.
Consistent with previously announced proof-of-concept data, the
study met its primary endpoint, with 16 of the 20 patients (80%)
achieving a hemoglobin increase of ≥1.0 g/dL from baseline at one
or more assessments during Weeks 4-12. Additionally, a sustained
hemoglobin response and improvements in hemolysis and ineffective
erythropoiesis were observed in both α- or β-thalassemia patients
treated with mitapivat. Mitapivat was well tolerated, and the
safety profile was consistent with previous studies. Mitapivat is a
first-in-class, investigational, oral, small molecule allosteric
activator of wild-type and a variety of mutated pyruvate kinase R
(PKR) enzymes.
“These data continue to validate the potential of PK activation
as an entirely new mechanism for treating thalassemia, a disease
for which there have been few medical advancements. In particular,
we are excited to see data generated, for the first time, in
α-thalassemia, demonstrating an increase in hemoglobin from
baseline in all five patients in this subgroup,” said Kevin Kuo,
M.D., hematologist at University Health Network, University of
Toronto, and an investigator in the study. “The impressive results
reported today underscore the potential of mitapivat to
meaningfully improve hallmarks of this disease, including hemolysis
and ineffective erythropoiesis.”
Mitapivat Phase 2 Proof-of-concept StudyThe
open-label Phase 2 study evaluated the efficacy, safety,
pharmacokinetics and pharmacodynamics of mitapivat treatment in
adults with either non-transfusion-dependent α- or β-thalassemia
who have a baseline hemoglobin (Hb) concentration of ≤10 g/dL. The
trial enrolled 20 patients. All patients were treated with an
initial dose of mitapivat 50 mg twice daily followed by a
dose-level increase to 100 mg twice daily at the Week 6 visit based
on safety evaluations and hemoglobin concentrations. Following the
completion of the 24-week core period, patients had the opportunity
to enroll in an optional 10-year extension period which will
evaluate long-term efficacy and safety of mitapivat in this
population.
- Of the 20 patients, 5 patients had α-thalassemia, and 15
patients had β-thalassemia.
- Median hemoglobin at baseline was 8.43 (range 5.13-9.8)
g/dL.
- Median age was 44 (range 29-67) years.
Efficacy Data
- The primary endpoint, defined as a ≥1.0 g/dL increase in
hemoglobin concentration from baseline at one or more assessments
between Week 4 and Week 12, was met by 16 of 20 (80%) patients
(1-sided p<0.0001), including all 5 (100%) α-thalassemia
patients and 11 of 15 (73.3%) β-thalassemia patients. The 1-sided
p-value associated with the test of H0: hemoglobin response rate
=30% vs H1: hemoglobin response rate >30%, based on the
Clopper-Pearson method.
- The secondary endpoint of sustained hemoglobin response,
defined as a primary endpoint response and a ≥1.0 g/dL increase in
hemoglobin concentration from baseline at two or more assessments
between Week 12 and Week 24, was met by 13 of 20 (65%) patients,
including all 5 (100%) α-thalassemia patients and 8 of 15 (53.3%)
patients with β-thalassemia.
- During Weeks 12-24, the mean hemoglobin change from baseline
was 1.3 g/dL. The mean change was 1.2 g/dL for α-thalassemia
patients, and 1.3 g/dL for β-thalassemia patients.
- Among hemoglobin responders, mean time to first ≥1.0 g/dL
increase in hemoglobin concentration was 4.5 weeks.
- Markers of hemolysis and erythropoiesis – including indirect
bilirubin, lactate dehydrogenase and erythropoietin – demonstrated
improvements that were consistent with the hemoglobin increase in
both α- and β-thalassemia patients.
- Adenosine triphosphate (ATP) levels showed mean increases of up
to 86.7% from baseline.
Safety DataThe majority of adverse events (AEs) observed were
consistent with previously published data for mitapivat in healthy
volunteers and patients with pyruvate kinase (PK) deficiency.
- Dose escalation to 100 mg twice daily was well tolerated.
- The most commonly reported AEs were initial insomnia (n=10
[50%]), dizziness (n=6 [30%]) and headache (n=5 [25%]).
- One patient (5%) discontinued treatment during the study; the
adverse event leading to study drug discontinuation was not
treatment-related.
- Seventeen patients continued to the extension period of the
study, and as of March 27, 2021, 17 patients remain on study
drug.
“We are pleased to present data from our Phase 2 trial of
mitapivat, which is the first clinical study of a PK activator in
thalassemia and the first drug trial in α-thalassemia, and
represents a potentially innovative therapeutic approach for these
patients who are in need of new treatment options,” said Chris
Bowden, chief medical officer at Agios. “Our focus now is to
advance the development of mitapivat in thalassemia as quickly and
efficiently as possible, with the initiation of two Phase 3 studies
of mitapivat, ENERGIZE and ENERGIZE-T, in not regularly transfused
and regularly transfused adults with thalassemia. Additionally, we
look forward to further advancing mitapivat as a potential
treatment for other underserved patients with hemolytic anemias,
including individuals with pyruvate kinase deficiency, where our
U.S. and EU regulatory filing plans are on track, and sickle cell
disease, where our pivotal development program is on track to
initiate by year-end.”
Oral Presentation Information
Title: Results from a Phase 2, open-label,
multicenter study of the oral pyruvate kinase activator mitapivat
in adults with non-transfusion dependent alpha- or
beta-thalassemiaLive Q&A Session Date and
Time: Tuesday, June 15, 2021, at 8:45 p.m. CEST / 2:45
p.m. ETOral Abstract Session: Changing the scene
on thalassemiasAbstract:
S267Presenter: Kevin H. M. Kuo, M.D., Division of
Hematology, University of Toronto, Toronto, Canada
Mitapivat Clinical DevelopmentIn addition to
the Phase 2 extension study of mitapivat in adults with
non-transfusion-dependent α- and β-thalassemia, Agios is initiating
two Phase 3 studies of mitapivat in adults with thalassemia in the
second half of 2021. They are:
- ENERGIZE: A placebo-controlled trial with a 2:1 randomization
evaluating patients who do not receive regular transfusions. The
primary endpoint of the trial is hemoglobin response, defined as a
≥1.0 g/dL increase in average hemoglobin concentration from Week 12
through Week 24 compared with baseline.
- ENERGIZE-T: A placebo-controlled trial with a 2:1 randomization
evaluating patients who receive regular transfusions. The primary
endpoint of the trial is transfusion reduction response, defined as
a ≥50% reduction in transfused red blood cell units with a
reduction of ≥2 units of transfused red blood cells in any
consecutive 12-week period through Week 48 compared with
baseline.
In addition to its Phase 2 study of mitapivat in adults with
non-transfusion-dependent α- or β-thalassemia, Agios has completed
two global, pivotal trials in adults with pyruvate kinase (PK)
deficiency. Final data from these studies will be presented in an
oral session at the EHA Virtual Congress. They are:
- ACTIVATE: A placebo-controlled trial with a 1:1 randomization
evaluating patients who do not receive regular transfusions. The
primary endpoint of the study was hemoglobin response, defined as a
≥1.5 g/dL increase in hemoglobin concentration from baseline that
is sustained at two or more scheduled assessments at Weeks 16, 20
and 24 during the fixed dose period.
- ACTIVATE-T: A single arm trial of regularly transfused patients
with a primary endpoint of reduction in transfusion burden, a
reduction of ≥33 percent in the number of red blood cell units
transfused during the 24-week fixed dose period compared with the
historical transfusion burden standardized to 24 weeks.
ACTIVATE and ACTIVATE-T are intended to support global
regulatory filings for mitapivat in adults with PK deficiency in
the U.S. in the second quarter of 2021 and in the EU in mid-2021.
Agios also is conducting an extension study for adults with PK
deficiency previously enrolled in ACTIVATE or ACTIVATE-T, which is
designed to evaluate the long-term safety, tolerability and
efficacy of treatment with mitapivat.
In addition, mitapivat is being evaluated as a potential
treatment for sickle cell disease under a Cooperative
Research and Development Agreement (CRADA) with
the U.S. National Institutes of Health. Mitapivat has
been shown to decrease 2,3-diphosphoglycerate (2,3-DPG) and
increase adenosine triphosphate (ATP), and through this mechanism,
it may reduce hemoglobin S polymerization and red blood cell
sickling. Preliminary clinical data establishing
proof-of-concept for mitapivat in sickle cell disease were
disclosed in June 2020, and updated data were
presented at the American Society of
Hematology (ASH) Annual Meeting in December 2020. Agios
is initiating its pivotal Phase 2/3 study in sickle cell disease by
year-end 2021.
Mitapivat has been granted orphan drug designation for the
treatment of PK deficiency by the U.S. Food and Drug
Administration (FDA) and the European Medicines Agency.
Additionally, mitapivat has received orphan drug designation from
the FDA for the treatment of thalassemia and sickle
cell disease.
Mitapivat is not approved for use by any regulatory
authority.
CONFERENCE CALL INFORMATION
Agios will host a virtual investor event today at 7:30 a.m.
ET to review the mitapivat clinical data. The event will be
webcast live and can be accessed under "Events & Presentations"
in the Investors and Media 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 genetically
defined diseases through scientific leadership in the field of
cellular metabolism. The company’s most advanced drug candidate is
a first-in-class pyruvate kinase R (PKR) activator, mitapivat, that
is currently being evaluated for the treatment of three distinct
hemolytic anemias. In addition to its active late-stage clinical
pipeline, Agios has multiple novel, investigational therapies in
clinical and preclinical development. For more information, please
visit the company’s website at www.agios.com.
Cautionary Note Regarding Forward-Looking
StatementsThis 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 Agios’ plans, strategies and expectations for the
preclinical, clinical and commercial advancement of its drug
development programs, including mitapivat; the potential benefits
of Agios’ products and product candidates, including mitapivat;
Agios’ key milestones and guidance for 2021; and the potential
benefits of Agios’ strategic plans and focus. The words
“anticipate,” “expect,” “goal,” “hope,” “milestone,” “plan,”
“potential,” “possible,” “strategy,” “will,” “vision,” 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. 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, without limitation risks and
uncertainties related to: the failure of Agios to receive milestone
or royalty payments related to the sale of its oncology business,
the uncertainty of the timing of any receipt of any such payments,
and the uncertainty of the results and effectiveness of the use of
proceeds from the transaction; the impact of the COVID-19 pandemic
to Agios’ business, operations, strategy, goals and anticipated
milestones, including its ongoing and planned research activities,
ability to conduct ongoing and planned clinical trials, clinical
supply of current or future drug candidates, commercial supply of
future approved products, and launching, marketing and selling
future approved products; 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, the EMA or
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 and 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 establish and maintain
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, or SEC, including
the risks and uncertainties set forth under the heading Risk
Factors in our filings with the SEC. While the list of factors
presented here is considered representative, this list should not
be considered to be a complete statement of all potential risks and
uncertainties. Any forward-looking statements contained in this
communication are made only as of the date hereof, and we undertake
no obligation to update forward-looking statements to reflect
developments or information obtained after the date hereof and
disclaim any obligation to do so other than as may be required by
law.
Contacts
Investors: 1AB Steve
Klasssteve@1abmedia.com
Media: 1AB Josie Butlerjosie@1abmedia.com
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