Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field
of cellular metabolism to treat cancer and rare genetic diseases,
today reported new data from the extension phase of the DRIVE PK
Phase 2 study of mitapivat (AG-348) in adults with pyruvate kinase
(PK) deficiency at the 2019 American Society of Hematology (ASH)
Annual Meeting. 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 that directly
targets the underlying metabolic defect in PK deficiency, a rare,
potentially debilitating, hemolytic anemia. In addition, data was
shared from the Agios-sponsored Natural History Study of PK
deficiency that detailed the comorbidities and complications
associated with the disease and the impact of transfusion history.
“DRIVE PK was the first clinical trial aimed at addressing the
metabolic defect in PK deficiency, and demonstrated that clinically
meaningful and robust increases in hemoglobin can be achieved with
an oral PKR activator,” said Eduard J. van Beers, M.D., Ph.D.,
University Medical Center Utrecht and an investigator in the study.
“These new data demonstrate that chronic treatment with mitapivat
is well tolerated and can lead to a reduction in hemolysis as
demonstrated by sustained improvements in hemoglobin and other
markers for more than three years.”
“As a rare hemolytic anemia, PK deficiency has historically been
under diagnosed and not well characterized. The new and emerging
data from the Natural History Study demonstrate that adults with PK
deficiency are at increased risk of comorbidities and complications
resulting from chronic hemolysis and iron overload, regardless of
transfusion history,” said Chris Bowden, M.D., chief medical
officer at Agios. “We are committed to advancing the first
potential disease-modifying therapy for these patients and are on
track to complete enrollment in both of our pivotal Phase 3 trials
of mitapivat in PK deficiency by the end of the year. In addition,
we are exploring the utility of wildtype PKR activation in other
hemolytic anemias, such as thalassemia and sickle cell
disease.”
Data from the Extension Phase of the DRIVE PK Study of
MitapivatDRIVE PK is an ongoing global, open-label, Phase
2, safety and efficacy study evaluating mitapivat in adults with PK
deficiency who do not receive regular transfusions. Patients were
randomly assigned to receive either 50 mg or 300 mg of mitapivat
twice daily for a 24-week core period and eligible patients could
continue treatment in an ongoing extension phase. In the extension
phase, patients treated with mitapivat doses >25 mg twice daily
in the core period undergo a dose taper and continue on a dose that
maintained their Hb level at no lower than 1.0 g/dL below their
pre-taper level. As of the March 27, 2019 data cutoff, 18 of the 36
patients remain in the extension phase with a median treatment
duration of 35.6 months (range 28.7-41.9).
For the 18 patients in the extension phase, improvements in
hemoglobin and other markers of hemolysis including reticulocytes,
indirect bilirubin and haptoglobin achieved during the core period
were sustained during the extension period up to 42 months, as of
the data cutoff.
Adverse events (AEs) for patients who continued in the study
(n=18) were comparable in the core and extension periods. In the
extension, the most common AEs were headache (39%), insomnia (28%),
fatigue (28%) and nasopharyngitis (28%). No new safety signals were
identified in the extension period.
Data from the Natural History Study Evaluating
Comorbidities and Complications in Adults with PK
DeficiencyThe ongoing PK Deficiency Natural History Study
(NHS) evaluated 254 patients (131 adults) at 31 centers in six
countries who enrolled from June 2014 through April 20172. Data
reported at ASH compare baseline rates of comorbidities and
complications in adult patients from the NHS with the general
population (U.S.-based IBM MarketScan® claims database), and assess
the impact of transfusion frequency on the prevalence of these
comorbidities and complications. Individuals from the general
population were matched 10:1 to patients with PK deficiency based
on age, gender and year of enrollment in the NHS. The analysis
showed that patients with PK deficiency, regardless of current or
prior transfusion status, have higher rates of the following
comorbidities and complications than observed in the general
population.
- Adults with PK deficiency had higher lifetime rates of
pulmonary hypertension (4.6% compared to 0.3% in the general
population), osteoporosis (15.6% compared to 0%) and liver
cirrhosis (5.6% compared to 0.4%).
- Adults with PK deficiency had higher rates of splenectomy (4.9%
compared to 0.2% in the general population), cholecystectomy (13.1%
compared to 3.6%) and gallstones (16.9% compared to 4.3%) over the
preceding eight years.
- Rates of current prophylactic antibiotic and anticoagulant use
were significantly higher among patients with PK deficiency.
- It was observed that for some conditions, a gradient is seen
across PK deficiency transfusion cohorts, with the highest rates
observed in patients who receive regular transfusions (≥ 6 per
year). However, even patients with PK deficiency who have never
received blood transfusion are at increased risk of complications
of the disease and its treatment.
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, Agios is conducting a Phase 2 study evaluating the
efficacy, safety, pharmacokinetics and pharmacodynamics of
treatment with mitapivat in adults with non-transfusion-dependent
β- and α-thalassemia (NTDT). The primary endpoint is hemoglobin
response, and approximately 17 participants with NTDT will be
enrolled. Mitapivat is also 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.
About Pyruvate Kinase Deficiency and Genetic
BackgroundPyruvate kinase (PK) deficiency is a rare,
inherited disease that presents as chronic hemolytic anemia, which
is the accelerated destruction of red blood cells. The inherited
mutations in PKR genes cause a deficit in cellular energy within
the red blood cell, as evidenced by lower PK enzyme activity, a
decline in adenosine triphosphate levels and a build-up of upstream
metabolites, including 2,3-DPG (2,3-diphosphoglycerate).
PK deficiency is associated with chronic hemolysis leading to
complications including gallstones, pulmonary hypertension,
extramedullary hematopoiesis, cirrhosis, osteoporosis, and iron
overload and its sequelae, which occur regardless of transfusion
burden. Current management strategies for PK deficiency, including
blood transfusion and splenectomy, are associated with both short-
and long-term risks.
More than 300 different mutations have been identified to date.
The mutations observed in PK deficiency patients are classified in
two main categories. A missense mutation causes a single amino acid
change in the protein, generally resulting in some functional
protein. A non-missense mutation is any mutation other than a
missense mutation, generally resulting in little functional
protein. It is estimated that 58 percent of patients with PK
deficiency have two missense mutations, 27 percent have one
missense and one non-missense mutation, and 15 percent have two
non-missense mutations1. For more information about PK deficiency,
including the signs and symptoms, how to test for it (including a
free testing option), and how it is currently managed, visit
knowpkdeficiency.com.
The Peak Registry, a global, longitudinal study of children and
adults with PK deficiency, has been established to better
understand the full spectrum of disease variability, including
impact on quality of life. The Registry is open and recruiting
patients. Learn more at www.peakregistry.com.
Investor Event and Webcast InformationAgios
will host an investor event today at 8:00 p.m. ET in Orlando, Fla.
to review the IDH and PKR data presented at ASH. 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 Agios Agios 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 and adjacent areas of biology. 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
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: 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.
______________________________ 1 Bianchi P et
al. poster, 2017 ASH Annual Meeting2 Grace RF et al. Blood
2018;131:2183-92
Investor & Media Contact:
Holly Manning, 617-844-6630 Associate Director, Investor Relations
Holly.Manning@agios.com
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