Constellation Pharmaceuticals, Inc., a clinical-stage
biopharmaceutical company using its expertise in epigenetics to
discover and develop novel therapeutics, today provided an update
of preliminary data from the MANIFEST clinical trial in oral and
poster presentations at the annual meeting of the American Society
of Hematology (ASH) in Orlando.
MANIFEST is an open-label Phase 2 clinical trial of the
Company’s bromodomain and extra-terminal domain (BET) protein
inhibitor CPI-0610 in patients with myelofibrosis (MF). Arm 3 is
evaluating CPI-0610 in combination with ruxolitinib in
JAK-inhibitor-naïve MF patients. Arms 1 and 2 are studying CPI-0610
as a monotherapy or in combination with ruxolitinib in
ruxolitinib-resistant or -intolerant MF patients.
The updated preliminary data presented at ASH showed signs of
clinical activity for CPI-0610 similar to that previously reported
at the annual meetings of the American Society for Clinical
Oncology (ASCO) and the European Hematology Association (EHA) and
in the ASH abstracts. The preliminary data included data on
additional patients and showed evidence of activity across a broad
range of myelofibrosis parameters in both JAK-inhibitor-naïve and
ruxolitinib-resistant or -intolerant patients.
“If trends in preliminary data from MANIFEST in
JAK-inhibitor-naïve patients are confirmed with further study,
CPI-0610 has the potential to transform the standard of care in
these patients," said Claire Harrison, D.M., Professor of
Haematology, and Clinical Director, Guy's and St Thomas' NHS
Foundation Trust, and a MANIFEST investigator.
“Preliminary data from MANIFEST in ruxolitinib-resistant or
-intolerant patients are encouraging, suggesting the potential
opportunity for a differentiated treatment option in such
patients,” said John Mascarenhas, M.D., Associate Professor, the
Icahn School of Medicine at Mount Sinai, and a MANIFEST
investigator.
The presentations at ASH reflect data as of an October 17, 2019,
data cutoff, updating preliminary data presented in ASH abstracts
published on November 6, 2019, as of a June 27, 2019, data
cutoff.
Below are highlights of the presentations at ASH:
JAK-Inhibitor-Naïve Patients (Arm 3)
- SVR35: Twelve out of 15 (80%) evaluable
JAK-inhibitor-naïve patients experienced SVR35 at 12 weeks. The
median percent change in spleen volume reduction was -49.7%.
- TSS50: Ten out of 14 (71%) evaluable
patients achieved at least a 50% improvement in Total Symptom Score
(TSS50) at 12 weeks. The median percent change in TSS at 12 weeks
was -60.3%.
Ruxolitinib-Resistant or -Intolerant Patients (Arms 1
and 2)
CPI-0610 Add-on to Ruxolitinib in Transfusion-Dependent Patients
(Cohort 2A)
- SVR35: At 24 weeks, SVR35 was achieved
in 3 out of 12 (25%) evaluable patients, with a median percent
change of -24.9%. An SVR35 at any time (best response) was achieved
in 5 out of 17 (29%) evaluable patients, with a best median percent
change of -21.2%.
- SVR: At 24 weeks, 11 out of 12 (92%) evaluable
patients had a spleen volume reduction.
- TSS50: At 24 weeks, TSS50 was achieved
in 7 out of 13 (54%) evaluable patients, with a median percent
change of -58.8%. A TSS50 at any time (best response) was achieved
in 13 out of 17 (76.5%) evaluable patients, with a median best
change of -71.0%.
- TD to TI: Conversion from transfusion
dependence (TD) to transfusion independence (TI) occurred in 6 out
of 14 (43%) evaluable patients with at least 24 weeks of
treatment.
Other Ruxolitinib-Resistant or -Intolerant Patients (Cohorts 1A,
1B, and 2B)
- SVR35: None of the patients in these
cohorts achieved SVR35 at 24 weeks. An SVR35 at any time (best
response) was achieved in 1 out of 4 evaluable patients in cohort
1A.
- SVR: Nine out of 13 (69%) evaluable
patients in Cohort 2B, 1 out of 2 (50%) evaluable patients in
Cohort 1A, and 5 out of 7 (71%) evaluable patients in Cohort 1B
achieved a spleen volume reduction at 24 weeks. The median
reductions were -10.9%, -3.2%, and -26.0%, respectively.
- TSS50: Five out of 13 (38%) evaluable
patients in Cohort 2B, 0 out of 1 evaluable patient in Cohort 1A,
and 3 out of 5 (60%) evaluable patients in Cohort 1B achieved a
TSS50 at 24 weeks. Median reductions were -44.1%, -18.4%, and
-53.5%, respectively.
- TD to TI: Zero out of 2 TD patients in cohort
1A with at least 24 weeks of treatment converted to TI.
Additional Data Supporting Possible Disease Modification
- Hemoglobin Improvement: Six out of 11
(55%) evaluable patients treated with CPI-0610 monotherapy and 2
out of 15 (13%) evaluable patients treated with CPI-0610 +
ruxolitinib achieved at least a 1.5 g/dL improvement in hemoglobin
without receiving a blood transfusion in the 12 weeks prior to
assessment.
- Bone Marrow Fibrosis Score Improvement:
Twelve out of 32 (38%) evaluable patients in Arms 1 and 2,
including 7 out 11 (63%) evaluable patients in Cohort 2A, achieved
at least a one-grade improvement in bone marrow fibrosis score. Ten
out of 12 improvements occurred within the first six months of
treatment.
Safety
- CPI-0610 in combination with ruxolitinib in JAK-inhibitor-naïve
patients (Arm 3) was generally well tolerated. No adverse events
led to study discontinuation. Three patients (10%) had ≥ Grade 3
anemia. One patient (3.3%) had Grade 4 thrombocytopenia, which was
reversible. The most common non-hematologic adverse events were
diarrhea, nausea, dizziness, and muscle spasms, which were
primarily Grade 1/2.
- CPI-0610 as monotherapy or in combination with ruxolitinib in
ruxolitinib-refractory or -intolerant patients (Arms 1 and 2) was
generally well tolerated. The most common hematologic adverse event
was thrombocytopenia. Nine patients (10%) had ≥ Grade 3
thrombocytopenia, none of which were serious adverse events. These
nine patients included two (5.6%) in Arm 1 and seven (12.9%) in Arm
2. The most common non-hematologic adverse events, primarily Grade
1/2, were diarrhea, nausea, cough, fatigue, vomiting, and upper
respiratory tract infection. Eight out of 90 (8.9%) patients
reported Grade 4 adverse events, all of which resolved. Of these
eight, four (11.1%) occurred in Arm 1, of which three required dose
interruption and one (rash) was considered related to CPI-0610, and
four (7.4%) occurred in Arm 2, none required dose reduction and one
(anemia) was considered related to the combination therapy. One
ruxolitinib-resistant or -intolerant patient (1.1%) discontinued
due to serious adverse event(s), which were reported as unlikely to
have been related to CPI-0610. Three out of 90 (3.3%)
ruxolitinib-resistant or -intolerant patients, all in Arm 2,
reported Grade 5 adverse events—acute kidney injury, traumatic
subdural hematoma (fall due to tripping), and brain stem hemorrhage
(no concomitant thrombocytopenia)—none of which were considered by
Constellation to be related to CPI-0610.
Orphan Drug Designation
- The U.S. Food and Drug Administration (FDA) granted Orphan Drug
Designation to CPI-0610 for the treatment of MF on November 20,
2019.
- The FDA Orphan Drug Designation program provides orphan status
to drugs and biologics that are defined as those intended for the
safe and effective treatment, diagnosis, or prevention of rare
diseases or disorders that affect fewer than 200,000 people in the
United States. Under specified conditions, this designation may
provide companies a seven-year marketing exclusivity period, as
well as certain incentives, including federal grants, tax credits,
and a waiver of Prescription Drug User Fee Act (PDUFA) filing
fees.
Future Plans
- Constellation continues to enroll patients in MANIFEST. As a
result of encouraging preliminary data, Constellation expanded Arm
3 of MANIFEST for JAK-inhibitor-naïve patients from 43 to up to 101
patients. The Company also expanded Cohort 2A, for TD
ruxolitinib-resistant or -intolerant patients adding CPI-0610 to
ruxolitinib, from 16 to up to 60 patients.
- Constellation has started planning for a randomized,
active-controlled, pivotal Phase 3 clinical trial studying the
combination of CPI-0610 and ruxolitinib versus ruxolitinib and
placebo in JAK-inhibitor-naïve patients with MF. The Company
expects this clinical trial to start in 2020.
Investor Event
- Constellation will host an analyst/investor event and webcast
today at 12:30 PM EST in Salon 2 at the Rosen Centre Hotel in
Orlando in conjunction with the annual meeting of the American
Society of Hematology. The event will be webcast live and can be
accessed on the Investor Relations section of Constellation’s
website at
http://ir.constellationpharma.com/events-and-presentations/events.
Analysts and investors may also access the event and participate in
the live question-and-answer session by dialing (877) 473-2077
(domestic) or (661) 378-9662 (international) and referring to
conference ID 7892044. A replay of the call will be available at
(855) 859-2056, (404) 537-3406, or (800) 585-8367.
About MANIFEST
MANIFEST is an open-label Phase 2 clinical trial of CPI-0610 in
patients with myelofibrosis (MF), a rare cancer of the bone marrow
that disrupts the body’s normal production of blood cells.
Constellation is evaluating CPI-0610 in combination with
ruxolitinib in JAK-inhibitor-naïve MF patients (Arm 3), with a
primary endpoint of the proportion of patients with a ≥35% spleen
volume reduction from baseline after 24 weeks of treatment.
Constellation is also evaluating CPI-0610, either as a monotherapy
in patients who are resistant to, intolerant of, or ineligible for
ruxolitinib and no longer on the drug (Arm 1), or as add-on therapy
in combination with ruxolitinib in patients with a sub-optimal
response to ruxolitinib or MF progression (Arm 2). Patients in Arms
1 and 2 are being stratified based on TD status. The primary
endpoint for the patients in cohorts 1A and 2A, who were TD at
baseline, is conversion to TI for 12 consecutive weeks. The primary
endpoint for the patients in cohorts 1B and 2B, who were not TD at
baseline, is the proportion of patients with a ≥35% spleen volume
reduction from baseline after 24 weeks of
treatment.
About Constellation Pharmaceuticals
Constellation Pharmaceuticals is a clinical-stage
biopharmaceutical company developing novel therapeutics that
selectively modulate gene expression to address serious unmet
medical needs in patients with cancer. The Company has a deep
understanding of how epigenetic and chromatin modifications in
cancer cells and in the tumor and immune microenvironment play a
fundamental role in driving disease progression and drug
resistance. Constellation is driving development of the BET
inhibitor CPI-0610 for the treatment of myelofibrosis as well as
the EZH2 inhibitors CPI-1205 and CPI-0209 for the treatment of
metastatic castration-resistant prostate cancer and other cancers.
The Company is also applying its broad research and development
capabilities to explore other novel targets that directly and
indirectly impact gene expression to fuel a sustainable pipeline of
innovative small-molecule product candidates.
Forward-Looking Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of 1995
that involve substantial risks and uncertainties, including
statements regarding the implications of preliminary or interim
clinical data, the development status of the Company’s product
candidates, and the Company’s plans for future data presentations.
All statements, other than statements of historical facts,
contained in this press release, including statements regarding the
Company’s strategy, future operations, future financial position,
prospects, plans and objectives of management, are forward-looking
statements. The words “anticipate,” “believe,” “continue,” “could,”
“estimate,” “expect,” “intend,” “may,” “plan,” “potential,”
“predict,” “project,” “should,” “target,” “will,” “would” and
similar expressions are intended to identify forward-looking
statements, although not all forward-looking statements contain
these identifying words. Any forward-looking statements are based
on management’s current expectations of future events and are
subject to a number of risks and uncertainties that could cause
actual results to differ materially and adversely from those set
forth in, or implied by, such forward-looking statements. These
risks and uncertainties include, but are not limited to, risks
associated with Constellation’s ability to: obtain and maintain
necessary approvals from the FDA and other regulatory authorities;
continue to advance its product candidates in clinical trials;
whether preliminary or interim data from a clinical trial will be
predictive of the final results of the trial; replicate in later
clinical trials positive results found in preclinical studies and
early-stage clinical trials of CPI-0610, CPI-1205, and CPI-0209;
advance the development of its product candidates under the
timelines it anticipates, or at all, in current and future clinical
trials; obtain, maintain, or protect intellectual property rights
related to its product candidates; manage expenses; and raise the
substantial additional capital needed to achieve its business
objectives. For a discussion of other risks and uncertainties, any
of which could cause the Company’s actual results to differ from
those contained in the forward-looking statements, see the “Risk
Factors” section, as well as discussions of potential risks,
uncertainties and other important factors, in the Company’s most
recent filings with the Securities and Exchange Commission,
including the Company’s Quarterly Report on Form 10-Q for the
quarter ended September 30, 2019. In addition, the forward-looking
statements included in this press release represent the Company’s
views as of the date hereof and should not be relied upon as
representing the Company’s views as of any date subsequent to the
date hereof. The Company anticipates that subsequent events and
developments will cause the Company’s views to change. However,
while the Company may elect to update these forward-looking
statements at some point in the future, the Company specifically
disclaims any obligation to do so. CPI-0610, CPI-1205, CPI-0209,
and other product candidates are investigational in nature and have
not yet been approved by the FDA or other regulatory
authorities.
Contacts
Ronald Aldridge Senior Director, Investor RelationsConstellation
Pharmaceuticals+1
617-714-0539ron.aldridge@constellationpharma.com
Lauren ArnoldMedia RelationsMacDougall Biomedical
Communications+1 781-235-3060larnold@macbiocom.com
Constellation Pharmaceut... (NASDAQ:CNST)
Graphique Historique de l'Action
De Juin 2024 à Juil 2024
Constellation Pharmaceut... (NASDAQ:CNST)
Graphique Historique de l'Action
De Juil 2023 à Juil 2024