Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in the field
of cellular metabolism pioneering therapies for rare diseases,
today announced that the Phase 2 portion of the global RISE UP
study of mitapivat in sickle cell disease met its primary endpoint
of hemoglobin response for patients in both the 50 mg and 100 mg
twice daily (BID) mitapivat arms. The safety profile for mitapivat
observed in the study was generally consistent with previously
reported data in other studies of sickle cell disease and other
hemolytic anemias. Improvements were observed in markers of
hemolysis and erythropoiesis and annualized rates of sickle cell
pain crises at both mitapivat doses compared to placebo. These
results support proceeding with the Phase 3 portion of the study.
“We are pleased with the results of the Phase 2 portion of the
RISE UP pivotal study in sickle cell disease, which bring us closer
to our goal of providing a novel oral therapy that may improve
anemia, reduce sickle cell pain crises and improve how patients
feel and function,” said Sarah Gheuens, M.D., Ph.D., chief medical
officer and head of R&D. “We are grateful to all of the
patients who participated in our trial, our collaborators, study
investigators and advisors in the patient and clinical communities
for their partnership in achieving this milestone. The Phase 2 RISE
UP data further enhance the consistency of the dataset for
mitapivat across a range of hemolytic anemias.”
“It gives me great satisfaction to see the positive results from
the Phase 2 portion of the RISE UP study. Mitapivat has a high
potential to address aspects of the disease of greatest concern to
patients,” said Modupe Idowu, M.D., associate professor at The
University of Texas Health Science Center at Houston and medical
director of UT Physicians Comprehensive Sickle Cell Center, UT
Houston. “Sickle cell disease is a complex and debilitating disease
characterized by anemia, pain crises, fatigue, cognitive effects
and more. The sickle cell community is in dire need of effective
disease-modifying therapies – particularly novel oral therapies –
to address these unmet needs. I look forward to continuing the
Phase 3 RISE UP study and am hopeful this will deliver a potential
new treatment option for sickle cell warriors.”
The data from the Phase 2 RISE UP study, representing the first
placebo-controlled trial of mitapivat in sickle cell disease,
underscore the potential of mitapivat to be a safe and effective
oral treatment option for people living with sickle cell disease.
Based on the data reported to date, Agios plans to proceed with the
Phase 3 portion of the RISE UP study, which is expected to enroll
198 patients. The operationally seamless Phase 2/3 study design
allows Agios to leverage and create efficiencies in the start and
conduct of the Phase 3 portion of RISE UP, with a goal of enrolling
the first patient in Q4 of this year, reporting the Phase 3 data in
2025 and potentially receiving U.S. approval in 2026.
Results for the Phase 2 portion of RISE UP were as follows:
- A total of 79 patients were enrolled in the Phase 2 portion of
the study, with 26 patients in the 50 mg BID mitapivat arm, 26
patients in the 100 mg BID mitapivat arm, and 27 patients in the
placebo arm.
- Treatment with mitapivat demonstrated a statistically
significant increase in hemoglobin response rate compared to
placebo. Hemoglobin response was defined as an increase of ≥1 g/dL
in average hemoglobin concentrations from Week 10 through Week 12
compared with baseline.
- 46.2 percent of patients (n=12) in the 50 mg BID mitapivat arm
and 50.0 percent of patients (n=13) in the 100 mg BID mitapivat arm
achieved a hemoglobin response, compared to 3.7 percent of patients
(n=1) in the placebo arm (2-sided p=0.0003 and 0.0001,
respectively).
- Over the course of this 12-week study, the annualized rates of
sickle cell pain crises for patients in the 50 mg BID and 100 mg
BID mitapivat arms were 0.83 and 0.51, respectively, compared to
1.71 for patients in the placebo arm.
- The safety profile for mitapivat observed in the study was
generally consistent with previously reported data in other studies
of sickle cell disease and other hemolytic anemias.
- There were no adverse events (AEs) leading to discontinuation
in either the mitapivat or the placebo arms.
- Of the 79 patients enrolled in the study, 73 continued into the
Phase 2 open-label extension period.
Given the promising data for both mitapivat dose arms, the
company will continue to analyze the study data over the coming
weeks to select a dose for the Phase 3 study. Agios plans to
present a full analysis of the RISE UP Phase 2 data at an upcoming
medical meeting.
About the Phase 2/3 RISE UP StudyThe Phase 2/3
RISE UP study is evaluating the efficacy and safety of mitapivat in
sickle cell disease patients who are 16 years of age or older, have
had between two and 10 sickle cell pain crises in the past 12
months, and have hemoglobin within the range of 5.5 to 10.5 g/dL
during screening. The Phase 2 and Phase 3 portions of the study are
being conducted under a single protocol. The two portions of the
study will enroll different participants and will achieve
operational efficiency through leveraging the same sites, vendors
and other resources.
The Phase 2 portion included a 12-week randomized,
placebo-controlled period in which participants were randomized in
a 1:1:1 ratio to receive 50 mg mitapivat twice daily, 100 mg
mitapivat twice daily or matched placebo. The primary endpoints
were hemoglobin response, defined as ≥1 g/dL increase in average
hemoglobin concentration from Week 10 through Week 12 compared to
baseline, and safety.
The Phase 3 portion includes a 52-week randomized,
placebo-controlled period in which participants will be randomized
in a 2:1 ratio to receive the selected dose of mitapivat or
placebo. The primary endpoints are hemoglobin response, defined as
≥1 g/dL increase in average hemoglobin from baseline to Week 52,
and annualized rate of sickle cell pain crises. Participants who
complete either the Phase 2 or Phase 3 portion will have the option
to move into a 216-week open-label extension period to receive
mitapivat.
About PYRUKYND®
(mitapivat)PYRUKYND is a pyruvate kinase activator
indicated for the treatment of hemolytic anemia in adults with
pyruvate kinase (PK) deficiency.
IMPORTANT SAFETY INFORMATIONAcute
Hemolysis: Acute hemolysis with subsequent anemia has been
observed following abrupt interruption or discontinuation of
PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing
PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue
treatment if possible. When discontinuing treatment, monitor
patients for signs of acute hemolysis and anemia including
jaundice, scleral icterus, dark urine, dizziness, confusion,
fatigue, or shortness of breath.
Adverse Reactions: Serious adverse reactions
occurred in 10% of patients receiving PYRUKYND in the ACTIVATE
trial, including atrial fibrillation, gastroenteritis, rib
fracture, and musculoskeletal pain, each of which occurred in 1
patient. In the ACTIVATE trial, the most common adverse reactions
including laboratory abnormalities (≥10%) in patients with PK
deficiency were estrone decreased (males), increased urate, back
pain, estradiol decreased (males), and arthralgia.
Drug Interactions:
- Strong CYP3A Inhibitors and Inducers: Avoid concomitant
use.
- Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg
twice daily.
- Moderate CYP3A Inducers: Consider alternatives that are not
moderate inducers. If there are no alternatives, adjust PYRUKYND
dosage.
- Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal
Contraceptives: Avoid concomitant use with substrates that have
narrow therapeutic index.
- UGT1A1 Substrates: Avoid concomitant use with substrates that
have narrow therapeutic index.
- P-gp Substrates: Avoid concomitant use with substrates that
have narrow therapeutic index.
Hepatic Impairment: Avoid use of PYRUKYND in
patients with moderate and severe hepatic impairment.
Please see full Prescribing
Information for PYRUKYND.
Conference Call InformationAgios will host a
webcast investor event today at 8:00 a.m. ET to review the RISE UP
Phase 2 data and next steps for the Phase 3 portion of the study.
The event 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 the pioneering leader in PK
activation and is dedicated to developing and delivering
transformative therapies for patients living with rare diseases. In
the U.S., Agios markets a first-in-class pyruvate kinase (PK)
activator for adults with PK deficiency, the first
disease-modifying therapy for this rare, lifelong, debilitating
hemolytic anemia. Building on the company's leadership in the field
of cellular metabolism, Agios is advancing a robust clinical
pipeline of investigational medicines with programs in alpha- and
beta-thalassemia, sickle cell disease, pediatric PK deficiency and
MDS-associated anemia. In addition to its clinical pipeline, Agios
has a PAH stabilizer in preclinical development as a potential
treatment for phenylketonuria (PKU) and deep scientific expertise
in classical hematology. 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 future clinical development of mitapivat in sickle cell
disease; 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 or its collaborators is
developing will successfully commence or complete necessary
preclinical and clinical development phases, 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: 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; 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 with
Servier; risks and uncertainties related to the impact of pandemics
or other public health emergencies 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; 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:
Investor ContactChris Taylor, VP Investor
Relations and Corporate CommunicationsAgios
PharmaceuticalsIR@agios.com
Media Contact Dan Budwick1AB Media
dan@1abmedia.com
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