Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in the field
of cellular metabolism pioneering therapies for rare diseases,
today presented detailed results from the Phase 2 portion of the
global RISE UP study of mitapivat in sickle cell disease in an oral
presentation (abstract #271) at the 65th American Society of
Hematology (ASH) Annual Meeting & Exposition, which is being
hosted Dec. 9-12, 2023, in San Diego.
During the Phase 2 double-blind, placebo-controlled study,
treatment with mitapivat demonstrated statistically significant
improvement in hemoglobin response across both mitapivat dose
levels (50 mg and 100 mg BID), compared to placebo. 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 annualized rates of sickle cell pain crises, and
markers of hemolysis and erythropoiesis for both mitapivat
treatment arms compared to placebo. Improvement in patient-reported
fatigue scores was observed with mitapivat 50 mg BID compared to
placebo.
“We are extremely pleased with the results of the Phase 2
portion of the RISE UP study and firmly believe that mitapivat has
the potential to be a meaningful therapy for the sickle cell
disease community,” said Sarah Gheuens, M.D., Ph.D., chief medical
officer and head of R&D. “The data further add to the
compelling and growing data set supporting the therapeutic
potential of mitapivat, which has demonstrated consistent clinical
and mechanistic improvements across three distinct hemolytic
anemias. We look forward to building on these data through the
Phase 3 portion of RISE UP and continuing to enroll patients around
the world in this study.”
“Sickle cell disease is a tremendously burdensome disease that
impacts all aspects of patients’ and families’ lives. New
therapeutic options – particularly those with convenient and easy
administration – are desperately needed for this underserved
community,” Modupe Idowu, M.D., professor at The University of
Texas Health Science Center at Houston and medical director of UT
Physicians Comprehensive Sickle Cell Center, UT Houston. “Currently
there are no approved oral therapies that address both sickle cell
pain crises and chronic anemia, two of the hallmark symptoms of the
disease. The RISE UP Phase 2 data suggest that mitapivat has the
potential to address both of these aspects with the convenience of
a pill. I look forward to supporting the Phase 3 portion of the
study and to potentially having a much-needed new medicine for
patients.”
Based on the Phase 2 data, Agios selected 100 mg BID as the
Phase 3 dose and is currently enrolling patients in this portion of
the RISE UP study. 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
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.
- Demographics and baseline characteristics for the participants
in each arm were as follows:
- Mean age (standard deviation) for participants in the 50 mg
BID, 100 mg BID, and placebo arms, respectively, was: 29.9 (7.79),
30.2 (10.52), and 28.5 (10.30) years.
- Percentage of female participants in the 50 mg BID, 100 mg BID,
and placebo arms, respectively, was: 57.7%, 61.5%, and 74.1%.
- Mean baseline hemoglobin (standard deviation) for participants
in the 50 mg BID, 100 mg BID, and placebo arms, respectively, was:
8.76 (1.295), 8.82 (0.898), and 8.49 (1.141) g/dL.
- Mean number of sickle cell pain crises during the previous year
(standard deviation) for participants in the 50 mg BID, 100 mg BID,
and placebo arms, respectively, was: 3.1 (1.83), 3.2 (1.65), and
3.4 (1.91).
- The study achieved its primary efficacy endpoint; 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% of patients (n=12) in the 50 mg BID mitapivat arm and
50.0% of patients (n=13) in the 100 mg BID mitapivat arm achieved a
hemoglobin response, compared to 3.7% of patients (n=1) in the
placebo arm (2-sided p=0.0003 and 0.0001, respectively).
- Least-squares mean (95% confidence interval) for average change
from baseline in hemoglobin levels, from Week 10 through Week 12,
for participants in the 50 mg BID, 100 mg BID, and placebo arms,
respectively, was: 1.11 (0.77, 1.45) g/dL, 1.13 (0.79, 1.47) g/dL,
and 0.05 (−0.28, 0.39) g/dL.
- The annualized rate of sickle cell pain crises (95% confidence
interval) for participants in the 50 mg BID and 100 mg BID, arms,
respectively, was 0.83 (0.34, 1.99) and 0.51 (0.16, 1.59), compared
to 1.71 (0.95, 3.08) for participants in the placebo arm.
- Least-squares mean (95% confidence interval) for average
changes from baseline in patient-reported fatigue score, from Week
10 through Week 12, for participants in the 50 mg BID, 100 mg BID,
and placebo arms, respectively, was: −3.80 (−7.16, −0.45), −0.10
(−3.27, 3.08), and −0.17 (−3.40, 3.07).
- 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.
- The most common treatment-emergent adverse events (TEAEs) in
the 50 mg BID, 100 mg BID, and placebo arms, respectively, were:
headache (n=6, 6, 7), arthralgia (n=3, 5, 9), dysmenorrhea (n=0, 3,
0), pain (n=3, 3, 2), pain in extremity (n=1, 3, 6), back pain
(n=4, 2, 3), nausea (n=1, 2, 4), fatigue (n=4, 1, 5), and
influenza-like illness (n=1, 1, 3).
- No serious TEAEs were attributed to mitapivat treatment.
- There were no adverse events leading to drug reduction,
discontinuation, interruption or death 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.
ASH Presentation DetailsTitle:
A Phase 2/3, Double-Blind, Randomized, Placebo-Controlled,
Multicenter Study of Mitapivat in Patients With Sickle Cell
Disease: RISE UP Phase 2 ResultsPresentation Time:
Saturday, Dec. 9, 2023, at 4:00 p.m. PTOral Abstract
Session: 114. Sickle Cell Disease, Sickle Cell Trait and
Other Hemoglobinopathies, Excluding Thalassemias: Clinical and
Epidemiological: Building on Momentum in Disease-Modifying
Therapeutics for Sickle Cell DiseaseAbstract:
271Presenter: Modupe Idowu, MD; McGovern Medical
School, UT Health, Houston, TX
Conference Call InformationAgios will host a
live investor event on Dec. 11, 2023, at 7:00 a.m.
PT in San Diego to review key oral and poster presentations
from this year’s ASH meeting, including the detailed RISE UP Phase
2 results. 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 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 100 mg of mitapivat twice daily or
matched 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 in the United States, and
for the treatment of PK deficiency in adult patients in
the European Union.
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 and Summary of
Product Characteristics for
PYRUKYND.
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 deep scientific
expertise in classical hematology and leadership in the field of
cellular metabolism and rare hematologic diseases, 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 is advancing a preclinical TMPRSS6
siRNA as a potential treatment for polycythemia vera, and a
preclinical PAH stabilizer as a potential treatment for
phenylketonuria (PKU). 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.
Moreover, there can be no guarantee that any medicines ultimately
commercialized by Agios will receive commercial acceptance. 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
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; 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; 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 key collaborations; uncertainty regarding any milestone or
royalty payments related to the sale of Agios’ oncology business or
its in-licensing of TMPRSS6 siRNA, and the uncertainty of the
timing of any such payments; uncertainty of the results and
effectiveness of the use of proceeds from the transaction with
Servier; competitive factors; 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
dan@1abmedia.com
Agios Pharmaceuticals (NASDAQ:AGIO)
Gráfico Histórico do Ativo
De Mai 2024 até Jun 2024
Agios Pharmaceuticals (NASDAQ:AGIO)
Gráfico Histórico do Ativo
De Jun 2023 até Jun 2024