-- Initiation of Monotherapy Efficacy Evaluation Follows
Selection of Recommended Phase 2 Dose in Dose-Escalation Stage
--
-- Proof-of-Mechanism Demonstrated by Desired Expansion of
Tumor-Killing Immune Cells
While Avoiding Activation of Immunosuppressive Cells --
DUBLIN, June 12, 2019 /PRNewswire/ -- Alkermes plc
(Nasdaq: ALKS) today announced the initiation of the monotherapy
expansion stage of its ARTISTRY-1 clinical trial to evaluate the
efficacy, safety and tolerability of ALKS 4230 in treating patients
with renal cell carcinoma or melanoma. Initiation of this portion
of the ongoing study follows the identification of 6 µg/kg/day
administered intravenously as the recommended monotherapy dose of
ALKS 4230 to evaluate in these select tumor types. The maximum
tolerated dose of ALKS 4230 has not yet been reached, and the
dose-escalation stage of the ARTISTRY-1 study is continuing. ALKS
4230 is a novel, engineered fusion protein designed to selectively
expand tumor-killing immune cells while avoiding the activation of
immunosuppressive cells by preferentially binding to the
intermediate-affinity interleukin-2 (IL-2) receptor complex.
"At the 6 µg/kg/day dose, data from the dose-escalation stage of
ARTISTRY-1 demonstrated the tolerability profile we set out to
achieve for ALKS 4230, along with desired lymphocyte cell expansion
without corresponding Treg activation. This validates
our design rationale for ALKS 4230, and we now look forward to
progressing into the expansion stage to evaluate ALKS 4230 as
monotherapy in select tumor types," said Craig Hopkinson, M.D., Chief Medical Officer and
Senior Vice President of Medicines Development and Medical Affairs
at Alkermes. "We plan to present the first efficacy data from
across the ALKS 4230 development program at a medical meeting later
this year, pending conference acceptance."
Selection of the recommended phase 2 dose of ALKS 4230 as
monotherapy was made following the completion of five
dose-escalation cohorts, spanning a dose range of 0.1 µg/kg/day to
6 µg/kg/day, in 36 patients who were refractory to prior
administered therapies known to demonstrate clinical benefit. Data
from the completed cohorts demonstrated dose-dependent
pharmacodynamic effects on circulating natural killer (NK) cells
and CD8+ T cells, and minimal and non-dose dependent
effects on immunosuppressive regulatory T cells (Tregs).
The newly initiated monotherapy expansion stage will assess
objective efficacy measures of ALKS 4230 administered intravenously
daily for five consecutive days in up to 105 patients refractory to
prior administered therapies with renal cell carcinoma or melanoma,
two tumor types for which high-dose IL-2 has demonstrated durable
anti-tumor responses as a monotherapy
treatment.1
Data from the initial four cohorts of the dose-escalation stage
of ARTISTRY-1 were presented at the 2018 Society for Immunotherapy
of Cancer (SITC) Annual Meeting. Treatment with ALKS 4230 at 3
µg/kg/day resulted in a dose-dependent increase in circulating NK
cells and CD8+ T cells with a near 4-fold and 2-fold
expansion, respectively, and minimal, non-dose-dependent change in
Tregs. Further effector-cell expansion was observed in
cohort 5 at the 6 µg/kg/day dose, with minimal increase in
circulating Tregs. No dose-limiting toxicities were
observed in cohort 5. Fever and chills were the most common
treatment-related adverse events (AEs) for ALKS 4230 across all
cohorts, and the safety profile observed with ALKS 4230 was
consistent with the known profile of cytokine therapy.
About ALKS 4230
ALKS 4230 is a novel, engineered fusion protein designed to
selectively expand tumor-killing immune cells while avoiding the
activation of immunosuppressive cells by preferentially binding to
the intermediate-affinity interleukin-2 (IL-2) receptor complex.
The selectivity of ALKS 4230 is designed to leverage the proven
anti-tumor effects of existing IL-2 therapy while mitigating
certain limitations.
About the ARTISTRY Clinical Program
ARTISTRY is an Alkermes-sponsored clinical program evaluating ALKS
4230 in patients with advanced solid tumors. ARTISTRY-1 is an
ongoing phase 1/2 study in which ALKS 4230 is administered as an
intravenous infusion daily for five consecutive days. ARTISTRY-1
has three distinct stages: an ongoing monotherapy dose-escalation
stage, the newly initiated monotherapy expansion stage and an
ongoing combination therapy stage with the PD-1 inhibitor
KEYTRUDA® (pembrolizumab) in patients with select
advanced solid tumors.
ARTISTRY-2 is an ongoing phase 1/2 study of ALKS 4230
administered subcutaneously as monotherapy and in combination with
pembrolizumab in patients with advanced solid tumors. ARTISTRY-2 is
designed to explore the safety, tolerability and efficacy of ALKS
4230 administered subcutaneously and assess once-weekly and
once-every-three-week dosing schedules.
About Alkermes
Alkermes plc is a fully integrated, global biopharmaceutical
company developing innovative medicines for the treatment of
central nervous system (CNS) diseases and oncology. The company has
a diversified commercial product portfolio and a substantial
clinical pipeline of product candidates for chronic diseases that
include schizophrenia, depression, addiction, multiple sclerosis
and cancer. Headquartered in Dublin,
Ireland, Alkermes plc has an R&D center in Waltham, Massachusetts; a research and
manufacturing facility in Athlone, Ireland; and a manufacturing facility in
Wilmington, Ohio. For more
information, please visit Alkermes' website at
www.alkermes.com.
Note Regarding Forward-Looking Statements
Certain statements set forth in this press release constitute
"forward-looking statements" within the meaning of the Private
Securities Litigation Reform Act of 1995, as amended, including,
but not limited to, statements concerning: the potential
therapeutic value of ALKS 4230; clinical development plans for ALKS
4230, including details of the ongoing ARTISTRY-1 and ARTISTRY-2
phase 1/2 studies and the company's plans for presentation of data
relating to the ARTISTRY development program. You are cautioned
that forward-looking statements are inherently uncertain. Although
the company believes that such statements are based on reasonable
assumptions within the bounds of its knowledge of its business and
operations, the forward-looking statements are neither promises nor
guarantees and are subject to a variety of risks and uncertainties,
many of which are beyond the company's control, which could cause
actual results to differ materially from those expressed or implied
in the forward-looking statements. These risks and uncertainties
include, among others, whether preclinical and early clinical
results for ALKS 4230, as a monotherapy or in combination with
pembrolizumab, will be predictive of future clinical study results;
whether ALKS 4230, as a monotherapy or in combination, could be
shown to be unsafe or ineffective; whether future clinical trials
or future stages of ongoing clinical trials for ALKS 4230, as a
monotherapy or in combination, will be initiated or completed on
time or at all; changes in the cost, scope and duration of
development activities for ALKS 4230; and those risks and
uncertainties described under the heading "Risk Factors" in the
company's Annual Report on Form 10-K for the year ended
Dec. 31, 2018 and in subsequent
filings made by the company with the U.S. Securities and Exchange
Commission (SEC), which are available on the SEC's website at
www.sec.gov. Existing and prospective investors are cautioned not
to place undue reliance on these forward-looking statements, which
speak only as of the date hereof. Except as required by law, the
company disclaims any intention or responsibility for updating or
revising any forward-looking statements contained in this press
release.
KEYTRUDA® is a registered trademark of Merck &
Co., Inc.
1 Rosenberg S. A. (2014). IL-2: the first effective
immunotherapy for human cancer. Journal of immunology
(Baltimore, Md.:
1950), 192(12), 5451–5458.
doi:10.4049/jimmunol.1490019
Alkermes Contacts:
For Investors: Sandy Coombs, +1 781 609 6377
For Media: Gretchen Murphy, +1 781 609 6419
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