SUZHOU, China and ROCKVILLE,
Md., June 17, 2024 /PRNewswire/ -- Ascentage
Pharma (6855.HK), a global biopharmaceutical company engaged in
developing novel therapies for cancer, chronic hepatitis B (CHB),
and age-related diseases, announced today that updated results from
three studies of olverembatinib (HQP1351), the first China-approved third-generation BCR-ABL1
inhibitor, have been released in posters at the 2024 European
Hematology Association Hybrid Congress (EHA 2024), taking place in
Madrid, Spain.
Building on the data reported at the 2023 American Society of
Hematology Annual Meeting, Ascentage Pharma has released the
updated median 1-year follow-up data of olverembatinib in patients
with chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic
leukemia (Ph+ ALL). In the results, olverembatinib showed excellent
durable clinical benefits and favorable long-term tolerability in
patients who had been treated with multiple TKIs (including those
who were resistant to ponatinib and/or asciminib), regardless of
whether they harbored the T315I mutation.
Dr. Elias Jabbour, MD,
Department of Leukemia, The University of
Texas MD Anderson Cancer Center, and the Principal
Investigator of the study, commented, "The study on
olverembatinib demonstrates significant efficacy and a manageable
safety profile in patients with heavily pretreated CML and Ph+ ALL,
including those with resistance or intolerance to ponatinib and
asciminib. These findings indicate that olverembatinib has the
potential to be a valuable treatment option for this challenging
patient population, warranting further investigation through
long-term studies to confirm its clinical benefits."
"Updates released at this year's EHA Hybrid Congress, combined
with previously reported data, reaffirmed the enormous potential of
olverembatinib in patients who are resistant to ponatinib and
asciminib," said Dr. Yifan Zhai,
Chief Medical Officer of Ascentage Pharma. "Moving forward, we
will expeditiously advance the clinical development of this global
best-in-class drug in efforts to bring a new treatment option to
patients as soon as possible."
Olverembatinib is a global best-in-class drug developed by
Ascentage Pharma. As the first China-approved third-generation BCR-ABL1
inhibitor, olverembatinib has been approved for two indications in
China, including adult patients
with tyrosine kinase inhibitor (TKI)-resistant chronic-phase CML
(CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I
mutation; and adult patients with CML-CP resistant to and/or
intolerant of first-and second-generation TKIs. Olverembatinib is
jointly commercialized in China by
Ascentage Pharma and Innovent Biologics. A global registrational
Phase III trial of olverembatinib in treatment-naïve patients with
Ph+ ALL is currently ongoing and could potentially lead
olverembatinib to become the first TKI approved in China for first-line treatment of Ph+ ALL.
The EHA Hybrid Congress is the largest gathering of the
hematology field in Europe. It
showcases the most cutting-edge research and state-of-the-art
innovative therapies, attracting over 10,000 clinical experts and
researchers from more than 100 countries every year. This year, in
addition to the latest data on olverembatinib, Ascentage Pharma
also released those of its Bcl-2 inhibitor lisaftoclax (APG-2575)
and the EED inhibitor APG-5918.
Highlights of those data of olverembatinib presented at EHA 2024
are as follows:
Olverembatinib Overcomes Ponatinib and Asciminib Resistance
in Patients (Pts) with Heavily Pretreated Chronic Myeloid Leukemia
(CML) and Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+
ALL)
- Abstract#: P722
- Presentation Type: Poster presentation
- Topic: Chronic myeloid leukemia – Clinical
- Date & Time: Friday June 14,
2024, 18:00 - 19:00 CEST
- Presenting Author: Dr. Elias Jabbour, Department of
Leukemia, The University of Texas MD
Anderson Cancer Center
Highlights:
- Background: Existing preclinical and clinical data show that
olverembatinib, an investigational, novel, potent BCR::
ABL1 TKI, has strong antitumor activity in CML or
Ph+ ALL.
- Introduction: This multicenter, open-label study was designed
to assess the safety, efficacy, and pharmacokinetic (PK) profiles
of olverembatinib in patients with heavily TKI (including ponatinib
and asciminib) pretreated CML or Ph+ ALL.
- Patient enrollment and methods: As of January 2, 2024, a total of 80 heavily TKI
pretreated patients, including 62 patients with CML-CP and 18
patients with advanced Ph+ leukemia (CML-AP, CML-BP, Ph+ ALL), were
enrolled. These patients were randomly assigned to receive orally
administered olverembatinib at 30, 40, or 50 mg once every other
day (QOD) in 28-day cycles.
- Efficacy results:
1) In patients with
CML-CP:
-
- 31/51 (60.8%) patients achieved a complete cytogenetic response
(CCyR), and 25/59 (42.4%) achieved a major molecular response
(MMR). No differences in the response rates of patients
with/without the T315I mutation were observed.
- In patients who failed prior treatment with ponatinib,
15/26 (57.7%) achieved a CCyR (including 10/19 [52.6%] patients
with prior resistance to ponatinib and 3/4 [75.0%] with prior
intolerance of ponatinib), and 11/30 (36.7%) patients achieved an
MMR (including 9/21 [42.9%] patients with prior resistance to
ponatinib and 1/6 [16.7%] with prior intolerance of
ponatinib).
- In patients who were asciminib-resistant, 4/8 (50.0%)
achieved a CCyR, and 4/12 (33.3%) achieved an MMR.
2) In patients with advanced
Ph+ leukemia:
-
- 3/14 (21.4%) patients achieved a CCyR, and 3/17 (17.6%)
patients achieved an MMR.
- Safety results:
- 72 (90.0%) patients experienced treatment emergent adverse
events (TEAEs) during their treatment with olverembatinib. Most of
the TEAEs were mild to moderate in severity.
- Common grade≥3 TEAEs included thrombocytopenia (17.5%),
neutropenia (12.5%), and increases in blood creatine phosphokinase
(12.5%). Serious adverse events occurring in ≥3 (3.8%) patients
included atrial fibrillation, COVID-19 infection, febrile
neutropenia, and intestinal obstruction. No treatment-related
adverse events (TRAE) led to death. Two (2.5%) patients experienced
Grade 1 treatment-related arterial occlusive events, one each with
angina pectoris and cardiac failure.
- Conclusions: Olverembatinib was efficacious and well tolerated
in patients with heavily TKI pretreated CML-CP and advanced Ph+
leukemias, including ponatinib- or asciminib-resistant/intolerant
disease.
Combination of Third Generation TKI Olverembatinib and
Chemotherapy or Blinatumomab for New Diagnosed Adult Ph+ ALL
Patients
- Abstract#: P427
- Presentation Type: Poster presentation
- Topic: Acute lymphoblastic leukemia – Clinical
- Date & Time: Friday June 14,
2024, 18:00 - 19:00 CEST
- Presenting Author: Junjie Chen, Nanfang Hospital, Southern
Medical University
Highlights:
- Background: TKIs have improved the long-term outcomes of
patients with Ph+ ALL, but resistance to TKIs remains a challenge.
Previous reports showed that third-generation TKI ponatinib,
combined with chemotherapy, results in a modest rate of complete
molecular response (CMR) of 75% in 3 months. Our recent study, a
front-line combination of olverembatinib and the PDT-ALL-2016
regimen in Ph+ ALL, had shown a promising outcome, achieving a CMR
rate of 84.6% at day 90. Furthermore, the combination of TKI and
blinatumomab (BITE) as a chemotherapy-free treatment approach has
demonstrated safety and effectiveness.
- Introduction: This study explored the clinical efficacy of the
front-line combination of olverembatinib and chemotherapy
(TKI+chemotherapy) or olverembatinib and blinatumomab (TKI+BITE)
for the treatment of Ph+ ALL.
- Patient enrollment and methods: From Jan
2022 to Dec 2023, 31 patients
with newly diagnosed Ph+ ALL treated with olverembatinib (40mg once
every other day) with pediatric-inspired chemotherapy (n=19;
PDT-ALL-2016 protocol) or blinatumomab (n=12; administered for a
total of 2 weeks followed by 2 weeks of break) were enrolled. The
median age was 40 years old, 15 (48.4%) patients had one comorbid
disease, and 8 (25.81%) patients had≥2 comorbid diseases.
- Efficacy results: With a median follow-up of 16 months, all
patients achieved a complete remission (CR) after one cycle of
treatment. For the entire cohort, 28 (90.3%) patients achieved a
CMR within 3 months. Among them, 16 (84.2%) and 12 (100.0%)
patients in the TKI + chemotherapy and TKI + BITE cohorts achieved
a CMR within 3 months, respectively. The 1-year overall survival
(OS) rate was 93.1% and event-free survival (EFS) rate was 78.4% in
the entire cohort. For the TKI + chemotherapy cohort, the 1-year OS
rate was 96.2% and the EFS rate was 71.5%. In the TKI + BITE
cohort, the 1-year OS rate was 100.0% and the EFS rate was
90.0%.
- Safety results: Adverse events were observed in 10 (32.3%)
patients: 3 patients (9.6%) developed septic shock during
treatment, 2 patients (6.4%) experienced mild pancreatitis, 2
patients (6.4%) experienced Pneumocystis jiroveci pneumonia,
2 patients (6.4%) experienced grade 2 cytokine release syndrome
(CRS), and 1 patient (3.2%) developed pulmonary embolism.
- Conclusions: This study showed the combination of
olverembatinib and chemotherapy or blinatumomab for treating adult
patients with Ph+ ALL. Among the 31 patients enrolled, a notable
rate of 1-year survival and CMR was observed, which holds promise
for improved long-term survival. Both the TKI + chemotherapy and
TKI + BITE cohorts showed good clinical outcomes, although the TKI
+ BITE cohort exhibited better survival than the TKI + chemotherapy
cohort. It is important to note that, although 74.19% of enrolled
patients had at least one comorbid disease and the median age was
40 years, the safety profile was acceptable.
Patient Reported Outcomes in Adults with TKI-Resistant
Chronic Myeloid Leukemia Receiving Olverembatinib-Therapy
- Abstract#: P1862
- Presentation Type: e-Poster presentation
- Topic: Chronic myeloid leukemia – Clinical
- Date & Time: 14, 2024, 18:00 - 19:00
CEST
- Presenting Author: Lu Yu, Peking
University People's Hospital
Highlights:
- Background: Third-generation (3G) TKIs have improved the
outcomes of patients with TKI-resistant CML. However, there are
very limited data on patient reported outcomes in adults receiving
3G TKIs such as olverembatinib.
- Introduction: The aim of this study was to assess
health-related quality of life (HRQoL), anxiety and depression
symptoms and identify variables associated with them in patients
with TKI-resistant CML receiving olverembatinib-therapy.
- Patient enrollment and methods:
- Subjects with TKI-resistance receiving olverembatinib in
the multicenter study were invited to complete the European
Organization for Research and Treatment of Cancer (EORTC) Quality
of Life Questionnaire (QLQ-C30), the Self-Rating Anxiety Scale
(SAS) and the Self-Rating Depression Scale (SDS) questionnaires at
baseline and regularly during the study treatment. The time trends
of the patient reported outcomes were estimated by a linear model
using the generalized estimating equation based on the independent
working correlation matrix. The generalized estimating equation
model was utilized to assess the impact of patients'
characteristics at baseline and treatment response during
olverembatinib therapy on HRQoL, SAS, and SDS.
- A total of 159 patients in CP or AP CML were included in
this study. Median (range) age was 42 (20-74) years. 104 (65%)
patients were male. Interval from diagnosis of CML to initiation of
olverembatinib therapy was 5 (0.3-23) years. 77 (48%) patients
received olverembatinib therapy within 5 years from the diagnosis
of CML. All patients completed the QLQ-C30 questionnaire; and 115
completed the SAS and SDS questionnaires.
- Survey results:
- Assessed by the EORTC QLQ-C30 questionnaire, the top 3
severe symptom burdens at baseline were financial difficulties,
fatigue, and insomnia. Eight scale items including global health,
physical functioning, emotional functioning, fatigue, pain,
dyspnea, diarrhea and financial difficulties improved significantly
during olverembatinib therapy. No scale deteriorated significantly.
In multivariate analysis, age < 40 years was associated with
better improvement of social functioning (p = 0.021); CP (vs. AP),
better improvement of dyspnea (p = 0.028) and diarrhea (p = 0.042);
achieving MMR, better improvement of global health (p = 0.005),
nausea and vomiting (p = 0.009), and diarrhea (p = 0.001).
- At baseline, 96 (84%) patients were normal according to
the SAS score; and 19 (16%) had mild or moderate anxiety
symptoms. 64 (56%) patients were normal according to the SDS score;
37 (32%) had mild depression symptoms; and 14 (12%), moderate or
severe depression symptoms. SAS score was decreased significantly
during olverembatinib therapy over time (p < 0.001) while the
SDS score did not change significantly. At 36 months on
olverembatinib therapy, 78 (95%) and 48 (59%) patients had no
anxiety and depression symptoms assessed by SAS and SDS
questionnaires, respectively. There was no variable identified that
impacted the change of SAS score during olverembatinib
therapy.
- Conclusions: HRQoL and anxiety symptoms significantly
improved over time during olverembatinib therapy in patients with
TKI-resistant CML. Younger age, CP than AP, and achieving MMR on
olverembatinib therapy were associated with better improvements of
HRQoL.
*Olverembatinib is an investigational drug that has not been
approved for any indication outside the Chinese mainland.
About Ascentage Pharma
Ascentage Pharma (6855.HK) is a globally focused
biopharmaceutical company engaged in developing novel therapies for
cancers, chronic hepatitis B, and age-related diseases. 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.
Ascentage Pharma focuses on developing therapeutics that inhibit
protein-protein interactions to restore apoptosis, or programmed
cell death. The company has built a pipeline of 9 clinical 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 tyrosine kinase inhibitors
(TKIs). Ascentage Pharma is also the registrational phase III
studies, in the US, Australia,
Europe, and China. Ascentage Pharma has been designated
for multiple Major National R&D Projects, including five Major
New Drug Projects, one New Drug Incubator status, four Innovative
Drug Programs, and one Major Project for the Prevention and
Treatment of Infectious Diseases.
Olverembatinib, the company's core drug candidate 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 2022 National Reimbursement
Drug List (NRDL). Furthermore, olverembatinib has been granted an
Orphan Drug Designation (ODD) 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 with numerous renowned
biotechnology and pharmaceutical companies and research institutes
such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo
Clinic, Dana-Farber Cancer Institute, MSD, and AstraZeneca. The
company has built a talented team with global experience in the
discovery and development of innovative drugs and is setting up its
world-class 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 or those of any of our Directors or
our Company are made as of the date of this article. Any of these
intentions may alter in light of future development.
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