Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field
of cellular metabolism to treat cancer and rare genetic diseases,
today reported interim data from its ongoing Phase 2 study
evaluating single agent mitapivat in non-transfusion-dependent α-
and β-thalassemia. Data from the study were featured in an oral
presentation at the 25th European Hematology Association Annual
Congress, which is being held virtually. 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.
“These data are exciting and further validate the potential of
PKR activation as an entirely new mechanism for treating
thalassemia, including α-thalassemia, for which there have been few
medical advancements,” said Kevin Kuo, M.D., hematologist at
University Health Network, University of Toronto, and an
investigator in the study. “Findings from the study indicate that
activation of wild-type PKR by mitapivat, an oral treatment option,
improved hemoglobin and associated markers of hemolysis and
erythropoiesis in patients with α- and β-thalassemia. In addition,
the safety profile was consistent with previously published data
for mitapivat.”
“We are pleased to share the impressive interim results from our
clinical study of mitapivat in α-and β-thalassemia, as the data
validate pre-clinical work conducted in our laboratories and with
academic collaborators and demonstrate the potential for PKR
activators in hemoglobinopathies such as thalassemia and sickle
cell disease,” said Chris Bowden, chief medical officer at Agios.
“Our focus now is to advance the development of mitapivat for these
patients as quickly and efficiently as possible. By the end of the
year, we expect to finalize a robust pivotal development plan that
spans both α-and β-thalassemia, as well as transfusion dependent
and non-transfusion dependent patients, with a goal of initiating a
pivotal program in 2021.”
Mitapivat Phase 2 Proof-of-concept Study
The ongoing, open-label Phase 2 study is evaluating the
efficacy, safety, pharmacokinetics and pharmacodynamics of
mitapivat treatment in adults with non-transfusion-dependent α- and
β-thalassemia who have a baseline hemoglobin (Hb) concentration of
≤10 g/dL. The trial is fully enrolled with 20 patients, and
includes a 24-week core period followed by a 2-year extension
period for eligible participants. 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 Hb concentrations.
As of the March 3, 2020 data cutoff, 18 patients were dosed and
13 were evaluable for the primary endpoint of a increase of ≥1.0
g/dL from baseline in at least one assessment during weeks
4-12.
- Of the 18 patients dosed, 5 patients have α-thalassemia, 4 of
which were evaluable for efficacy at the 12 week timepoint, and 13
patients have β-thalassemia, 9 of which were efficacy
evaluable.
- Median Hb at baseline was 8.43 (range 5.6-9.8) g/dL.
- Median treatment duration was 20.6 (range 1.1-50.0) weeks.
- Median age was 43.5 (range 29-67) years.
Efficacy Data
Efficacy data from the 13 efficacy evaluable patients as of the
data cutoff demonstrated:
- The primary endpoint defined as a ≥1.0 g/dL increase in Hb
concentration from baseline at 1 or more assessments between week 4
and week 12 was met by 12 of 13 (92.3%) patients who had completed
12 weeks of treatment, including all 4 (100%) α-thalassemia
patients and 8 of 9 (88.9%) patients with β-thalassemia.
- For the 9 β-thalassemia patients who completed 24 weeks of
treatment, 8 of 9 achieved a Hb response defined as ≥1.0 g/dL
increase in Hb concentration from baseline at 1 or more assessments
between week 12 and week 24. Seven of 8 patients met the criteria
for sustained response defined as primary response and Hb response
in ≥2 assessments during weeks 12-24.
- The mean Hb change from baseline for all 13 efficacy evaluable
patients was 1.34 g/dL over weeks 4-12. The mean change for
α-thalassemia patients was 1.17 g/dL over weeks 4-12, and 1.43 g/dL
for β-thalassemia patients over weeks 4-24.
- Median (range) time to Hb increase of >1 g/dL among the Hb
responders was 3.1 (1.4-7.1) weeks.
- Preliminary results for markers of hemolysis and erythropoiesis
demonstrated improvements that were consistent with the Hb
increase. Indirect bilirubin and lactate dehydrogenase showed
declines in α- and β-thalassemia patients, and erythropoietin
achieved near normal levels in both groups by week 6.
- Preliminary analysis of adenosine triphosphate (ATP) levels
showed mean increases of up to 92%, consistent with mitapivat’s
enhancement of glycolysis.
Safety Data
The safety analysis conducted on the 18 patients dosed as of the
data cutoff demonstrated that the majority of adverse events (AEs)
were consistent with previously published Phase 2 data for
mitapivat in patients with pyruvate kinase (PK) deficiency.
- Grade 3 AEs were reported in two patients and neither was
judged to be related to treatment.
- There were no serious adverse events (SAEs) and no AEs leading
to treatment discontinuation. Post-data cutoff, one Grade 3 AE of
renal dysfunction was reported, which was judged to be related to
treatment by the investigator and resolved upon treatment
discontinuation.
- Dose escalation to 100 mg twice daily was well tolerated and
not associated with an increase in AEs.
Mitapivat Clinical Development Agios has two
ongoing global, pivotal trials in adults with PK deficiency that
are fully enrolled.
- ACTIVATE: A placebo-controlled trial with a 1:1 randomization
evaluating 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 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, mitapivat is also being studied in sickle cell
disease under a Cooperative Research and Development Agreement with
the U.S. National Institutes of Health. Preliminary data
establishing proof-of-concept for mitapivat in sickle cell disease
were also disclosed today.
Mitapivat is not approved for use by any regulatory
authority.
Investor Webcast InformationAgios will host an
investor webcast today at 7:30 a.m. ET to review the mitapivat
proof-of-concept data in sickle cell disease and Phase 2
thalassemia data presented at EHA. The event will be webcast live
and can be accessed under "Events & Presentations" in the
Investors section of Agios’ website at www.agios.com. The archived
webcast will be available on Agios’ website beginning approximately
two hours after the event.
About AgiosAgios is focused on discovering and
developing novel investigational medicines to treat malignant
hematology, solid tumors and rare genetic diseases through
scientific leadership in the field of cellular metabolism. In
addition to an active research and discovery pipeline across these
three therapeutic areas, Agios has two approved oncology precision
medicines and multiple first-in-class investigational therapies in
clinical and/or 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: 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, without limitation:
risks and uncertainties related to 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 current or future approved products, and launching,
marketing and selling current or 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 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, except as
required by law.
Contacts
Investors:Holly Manning, 617-844-6630Director,
Investor RelationsHolly.Manning@agios.com
Media:Jessica Rennekamp, 857-209-3286Associate
Director, Corporate CommunicationsJessica.Rennekamp@agios.com
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