ROCKVILLE, Md. and SUZHOU, China, Aug. 12,
2024 /PRNewswire/ -- Ascentage Pharma (6855.HK),
a global, integrated biopharmaceutical company engaged in
discovering, developing and commercializing both first- and
best-in-class therapies for malignancies, announced today it has
been cleared by the Center for Drug Evaluation (CDE) of China
National Medical Products Administration (NMPA) to initiate a
registrational Phase III study of lisaftoclax (APG-2575), one of
the company's key drug candidates, in combination with azacitidine
(AZA) for the first-line treatment of newly-diagnosed patients with
higher-risk myelodysplastic syndrome (MDS). This clears the fourth
registrational Phase III study of lisaftoclax, marking another
major milestone in the clinical development of the drug.
This study (GLORA-4) is a multi-center, randomized,
double-blind, pivotal registrational Phase III trial to evaluate
the efficacy of lisaftoclax in combination with AZA in
newly-diagnosed adult patients with higher-risk MDS.
As a heterogeneous myeloid clonal disease originating from
hematopoietic stem cells, MDS commonly occurs in older population
with a median age of onset of 70 years and an incidence rate that
increases with age.1 MDS is characterized by the
abnormal growth of myeloid cells. Its clinical manifestations
include hematopoietic failure, refractory cytopenia, and the
propensity for high-risk patients to progress to acute myeloid
leukemia (AML). Data show that approximately 10% of low-risk
patients and 50% of high-risk patients with MDS would progress to
AML and thereafter face a dismal prognosis.2
At present, there are limited treatment options for patients
with MDS and the treatment outcome for most patients remains
relatively poor. Demethylation agents (AZA or decitabine) are the
current standard first-line treatment for patients with higher-risk
MDS. Studies showed that compared to conventional care regimens,
monotherapy with AZA can improve the overall survival of patients
with MDS.3 Allogeneic hematopoietic stem cell
transplantation (allo-HSCT) is the only available curative
treatment for MDS. However, the complex characteristics of MDS and
the old ages of patients have resulted in the intolerability of
chemotherapies that limited the rate of transplantation, and the
high rate of transplantation-associated mortality among patients
with MDS. The low survival rate of patients with higher-risk MDS
underscores an urgent unmet medical need for novel therapies and
medicines that can offer higher efficacies.
Lisaftoclax is a novel, orally administered Bcl-2 selective
inhibitor being developed by Ascentage Pharma to treat the patients
with malignancies by selectively blocking the antiapoptotic protein
Bcl-2 and hence restoring the normal apoptosis process in cancer
cells. Lisaftoclax is expected to be the first Bcl-2 inhibitor for
which an NDA will be filed for chronic lymphocytic leukemia
(CLL)/ small lymphocytic lymphoma (SLL) in China and the second anywhere globally that
has demonstrated clinical activity for the treatment of patients
with CLL and entered pivotal registrational studies. In published
clinical results released at the 2023 American Society of
Hematology (ASH) Annual Meeting, the drug candidate lisaftoclax has
demonstrated clinical benefit and tolerability in patients
with higher-risk MDS.4
"There is considerable unmet clinical need for patients with
MDS. Lisaftoclax, a Bcl-2 inhibitor, has already shown promising
clinical benefit and tolerability in early studies in patients with
MDS," said Dr. Yifan Zhai, Chief
Medical Officer of Ascentage Pharma. "We are very encouraged by
this approval for initiation of the registrational Phase III study
in the first-line treatment of patients with higher-risk MDS, as it
clears the way for the fourth registrational Phase III study of
lisaftoclax. Fulfilling our mission of addressing unmet clinical
needs in China and around the
world, we will actively press ahead with the clinical trials of
lisaftoclax for the benefit of more patients."
*Lisaftoclax is an investigational drug that has not been
approved in any country or region.
References:
- Fenaux P, Haase D, Santini V, et al. Myelodysplastic syndromes:
ESMO Clinical Practice Guidelines for diagnosis, treatment and
follow-up. Ann Oncol. 2021 Feb;32(2):142-156. doi:
10.1016/j.annonc.2020.11.002.
- NCCN Guidelines® Version 1.2023 on Myelodysplastic
Syndromes
- Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. International
Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine
compared with that of conventional care regimens in the treatment
of higher-risk myelodysplastic syndromes: a randomised, open-label,
phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. doi:
10.1016/S1470-2045(09)70003-8.
- Wang H, Wei X, Jiang Q, et al. Safety and Efficacy of
Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor (BCL-2i), in
Relapsed or Refractory (R/R) or Treatment-Naïve (TN) Patients (Pts)
with Acute Myeloid leukemia (AML), Myelodysplastic Syndrome (MDS),
or Other Myeloid Neoplasms. Blood (2023) 142 (Supplement 1): 2925.
https://doi.org/10.1182/blood-2023-188489
About Ascentage Pharma
Ascentage Pharma (6855.HK) is a global, integrated
biopharmaceutical company engaged in discovering, developing and
commercializing both first-in-class and best-in-class therapies to
address global unmet medical needs primarily in malignancies. On
October 28, 2019, Ascentage Pharma
was listed on the Main Board of the Stock Exchange of Hong Kong
Limited with the stock code 6855.HK.
The company has built a pipeline of 9 clinical-stage drug
candidates, including novel, highly potent Bcl-2 and dual
Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and
MDM2-p53 pathways, and next-generation TKIs. Ascentage Pharma is
also the only company in the world with active clinical programs
targeting all three known classes of key apoptosis regulators. The
company has conducted more than 40 clinical trials in the US,
Australia, Europe, and China, including 11 registrational studies
(completed/ ongoing/planned).
Olverembatinib, the company's first lead asset developed for the
treatment of drug-resistant chronic myeloid leukemia (CML) and the
company's first approved product in China, has been granted Priority Review
Designations and Breakthrough Therapy Designations by the Center
for Drug Evaluation (CDE) of China National Medical Products
Administration (NMPA). To date, the drug had been included into the
China National Reimbursement Drug List (NRDL). Furthermore,
olverembatinib has been granted Orphan Drug Designations (ODDs) and
a Fast Track Designation (FTD) by the US FDA, and an Orphan
Designation by the EMA of the EU.
To date, Ascentage Pharma has obtained a total of 16 ODDs from
the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of
the company's investigational drug candidates. Leveraging its
robust R&D capabilities, Ascentage Pharma has built a portfolio
of global intellectual property rights and entered into global
partnerships and other relationships with numerous leading
biotechnology and pharmaceutical companies such as Takeda,
AstraZeneca, Merck, Pfizer and Innovent; and research and
development relationships with leading research institutions such
as Dana-Farber Cancer Institute, Mayo Clinic, MD Anderson Cancer
Center, National Cancer Institute and the University of Michigan.
The company has built a talented team with a wealth of global
experience in the discovery and development of innovative drugs and
fully functional commercial manufacturing and Sales & Marketing
teams. One pivotal aim of Ascentage Pharma is to continuously
strengthen its R&D capabilities and accelerate its clinical
development programs, in order to fulfil its mission of addressing
unmet clinical needs in China and
around the world for the benefit of more patients.
Forward-Looking Statements
The forward-looking statements made in this article relate only
to the events or information as of the date on which the statements
are made in this article. Except as required by law, Ascentage
Pharma undertakes no obligation to update or revise publicly any
forward-looking statements, whether as a result of new information,
future events, or otherwise, after the date on which the statements
are made or to reflect the occurrence of unanticipated events. You
should read this article completely and with the understanding that
our actual future results or performance may be materially
different from what we expect. In this article, statements of, or
references to, our intentions and expectations or those of any of
our Directors or our Company are made as of the date of this
article. Any of these intentions and expectations may alter in
light of future development.
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