– Safety and Efficacy Profile Consistent with
Previously Reported Data –
Agios Pharmaceuticals, Inc. (Nasdaq:AGIO) presented updated data
today from its wholly owned pyruvate kinase-R (PKR) activator,
AG-348, demonstrating its potential as the first disease-modifying
treatment for patients with pyruvate kinase (PK) deficiency at the
2017 American Society of Hematology (ASH) Annual Meeting and
Exposition. PK deficiency is a rare, potentially debilitating,
congenital anemia.
DRIVE PK is an ongoing global open-label, Phase 2, safety and
efficacy trial evaluating AG-348 in 52 adult,
transfusion-independent patients with PK deficiency. As of the July
14, 2017 data cut-off 43 patients had completed the six-month core
dosing period and 9 patients discontinued treatment during the core
dosing period. Of the 52 patients enrolled, 26 (50%)
experienced a maximum hemoglobin (Hb) increase from baseline of
>1.0 gram per deciliter (g/dL) during the six-month core
period. For the 42 patients enrolled with at least 1 missense
mutation, 25 (60%) experienced a maximum Hb increase from baseline
of >1.0 g/dL. AG-348 remains well-tolerated with the majority of
adverse events (AEs) being Grade 1 or 2. The median treatment
duration was 37.5 weeks, with a maximum of 92.4 weeks.
“With some patients approaching two years of treatment, we are
encouraged that AG-348 continues to be well-tolerated and
demonstrates clinically relevant, sustained increases in hemoglobin
in adults with PK deficiency,” said Rachael Grace, M.D., of the
Dana-Farber Boston Children's Cancer and Blood Disorder Center and
a principal investigator for the study. “AG-348 has the potential
to be the first therapy for patients with PK deficiency that
targets the underlying cause of this chronic anemia and its
associated complications.”
Patients in DRIVE PK were randomized to a starting dose of 50 mg
or 300 mg twice daily, treated for six months in a core treatment
period and then offered treatment in an extension period.
Enrollment was completed in November 2016 with 52 patients.
Nine subjects discontinued during the core treatment period.
Thirty-six of 43 patients who completed the six month core
treatment period entered the extension period. As of the data
cut-off, 29 patients remain on treatment in the extension
period.
“DRIVE PK has established a clear signal of activity for AG-348
in PK deficiency and was instrumental in informing the design of
the pivotal program we are on track to initiate in the first half
of 2018,” said Chris Bowden, M.D., chief medical officer at Agios.
“In addition to this clinical work, our planned global PKD patient
registry will complement our patient finding efforts and further
advance our understanding of the disease burden for this rare
anemia.”
Safety Data
A safety analysis conducted for all 52 treated patients as of
the data cut-off shows that AG-348 continues to be well
tolerated.
- The majority of treatment-related AEs were Grade 1-2; the most
frequent were headache, insomnia and nausea.
- As previously reported, four patients experienced
treatment-related AEs leading to discontinuation: pleural effusion
(n=1), hypertriglyceridemia (n=1), pharyngitis/nausea (n=1) and
anemia (n=1).
- As previously reported, four patients experienced
treatment-related serious adverse events: withdrawal hemolysis
followed by anemia (n=1), anemia (n=1), osteoporosis (n=1) and
hypertriglyceridemia (n=1).
- A previously reported case of drug-related pharyngitis (n=1)
was subsequently deemed unrelated to study drug.
- Measurements of hormone levels in men at doses ≤50 mg BID
suggest mild aromatase inhibition by AG-348; ongoing follow-up will
continue to assess potential clinical significance.
Efficacy Data
In the efficacy analysis 26 of 52 patients (50%) overall and 25
of 42 patients (60%) with at least one missense mutation achieved
rapid and sustained Hb increases from baseline of >1.0 g/dL as
of the data cut-off.
- In patients who had Hb increases of >1.0 g/dL, the mean
maximum Hb increase was 3.4 g/dL (range 1.1-5.8 g/dL).
- The median time to first Hb increase of >1.0 g/dL was 10
days (range 7–187 days).
- As previously reported, the median baseline Hb in patients who
experienced a maximum Hb increase of >1.0 g/dL was 9.7 g/dL
(range 7.3–12.3 g/dL) vs. 8.0 g/dL (range 6.5–10.1 g/dL) in
patients who did not experience the increase.
Pivotal Development Plan
Agios plans to initiate two global, pivotal trials in adults
with PK deficiency in the first half of 2018 based on transfusion
status:
- A randomized, placebo-controlled trial with a 1:1 randomization
known as ACTIVATE is 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 ≥1.5 g/dL.
- A single arm trial of approximately 20 regularly transfused
patients known as ACTIVATE-T will have a primary endpoint of
reduction in transfusion burden over six months.
About Pyruvate Kinase Deficiency and Genetic
Background
PK deficiency is a rare inherited disease that presents as
hemolytic anemia, which is the accelerated destruction of red blood
cells. The inherited mutations in PKR enzymes cause a deficit in
cellular energy within the red blood cell, as evidenced by lower
pyruvate kinase enzyme activity and a decline in ATP (adenosine
triphosphate) levels and a build-up of upstream metabolites,
including 2,3-DPG (2,3-diphosphoglycerate).
The current standard of care for PK deficiency is supportive,
including blood transfusions, splenectomy, chelation therapy to
address iron overload and/or interventions for other treatment- and
disease-related morbidities. There is no approved therapy to treat
the underlying cause of PK deficiency.
PK deficiency is an autosomal recessive disease whereby all
patients inherit two mutations, one from each parent. More than 250
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.
Boston Children’s Hospital, in collaboration with Agios, is
conducting a Natural History Study to better understand the
symptoms and complications of PK deficiency, identify patients and
treatment centers, and capture other clinical data, including
quality of life measures and genetic information.
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.
In addition to an active research and discovery pipeline across
both therapeutic areas, Agios has multiple first-in-class
investigational medicines 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
Statements
This 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 AG-348; Agios’ plans for the further clinical
development of AG-348; 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, such as its agreements with
Celgene; 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 Meeting
Contacts
Investors:Renee Leck, 617-649-8299Senior Manager, Investor &
Public RelationsRenee.Leck@agios.com
Media:Holly Manning, 617-844-6630Associate Director, Corporate
CommunicationsHolly.Manning@agios.com
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