MANIFEST-2 met primary endpoint, nearly
doubling SVR35 response rate (66% versus 35%)
The key secondary endpoints assessing symptom
reduction, TSS50 and absolute change in TSS, showed significant
improvements for intermediate-risk patients (p<0.05, p<0.02,
respectively) and strong numerical improvements for overall
population
Pelabresib plus ruxolitinib showed clinically
meaningful anemia improvement versus placebo and ruxolitinib
Safety results were consistent with prior
clinical trials, with no new safety signals
MorphoSys intends to submit for approval in the
U.S. and Europe in mid-2024
Company to host conference call and webcast on
Tuesday, November 21, at 2:00 p.m. CET (1:00 p.m. GMT; 8:00 a.m.
EST)
MorphoSys AG (FSE: MOR; NASDAQ: MOR) today announced strong
topline results from the Phase 3 MANIFEST-2 study investigating
pelabresib, an investigational BET inhibitor, in combination with
the JAK inhibitor ruxolitinib compared with placebo plus
ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis.
MANIFEST-2 met its primary endpoint, as the combination therapy
demonstrated a statistically significant and clinically meaningful
improvement in the proportion of patients achieving at least a 35%
reduction in spleen volume (SVR35) at week 24. The key secondary
endpoints assessing symptom improvement – proportion of patients
achieving at least a 50% reduction in total symptom score (TSS50)
and absolute change in total symptom score (TSS) from baseline at
week 24 – showed a strong positive trend favoring the pelabresib
and ruxolitinib combination. In an analysis of patients classified
as intermediate risk (Dynamic International Prognostic Scoring
System [DIPSS] Int-1 and Int-2) – constituting more than 90% of
patients in MANIFEST-2 – the combination therapy demonstrated
significant improvements in both key secondary endpoints. DIPSS was
a pre-defined stratification factor in the MANIFEST-2 study
protocol.
“We are very pleased with this positive outcome. Pelabresib in
combination with ruxolitinib demonstrated strong reductions in
spleen volume and symptoms over ruxolitinib monotherapy – the most
impressive benefits seen in clinical studies of patients with
myelofibrosis,” said Jean-Paul Kress, M.D., Chief Executive Officer
of MorphoSys. “Importantly, we saw significant symptom improvements
for the vast majority of patients in the study. We look forward to
our continued conversations with regulatory agencies and intend to
file for approval in the U.S. and Europe.”
MANIFEST-2 Topline Results Overview
MANIFEST-2 is a global, multicenter, double-blind, Phase 3 study
that randomized 430 JAK inhibitor-naïve adult myelofibrosis
patients, making it one of the largest myelofibrosis studies
conducted to date.
Significant Improvement in Spleen Volume Reduction
In MANIFEST-2, 66% of patients receiving pelabresib in
combination with ruxolitinib achieved SVR35 at week 24, the primary
endpoint, versus 35% of those receiving placebo and ruxolitinib,
nearly doubling SVR35 response rates (95% CI [21.6; 39.3],
p<0.001).
“I believe MANIFEST-2 provides us with valuable evidence that
the addition of pelabresib offers meaningful improvements over JAK
inhibitor monotherapy as a first-line approach for patients with
myelofibrosis,” said John Mascarenhas, M.D., Director of the Adult
Leukemia Program at The Tisch Cancer Institute at Mount Sinai, New
York. “The pelabresib and ruxolitinib combination therapy
significantly reduced spleen volume – the best prognostic indicator
we have at our disposal for long-term myelofibrosis patient
outcomes. Based on insights from MANIFEST-2, pelabresib represents
a promising and well-tolerated therapeutic option for a community
in need of innovation.”
Meaningful Improvements to Myelofibrosis Symptoms
In a key secondary endpoint, TSS was reduced by 15.99 points at
week 24, from 28.26 at baseline, in the pelabresib and ruxolitinib
treatment arm and by 14.05 points at week 24, from 27.36 from
baseline, in the placebo plus ruxolitinib arm (Δ -1.94, 95% CI
[-3.92; 0.04], p=0.0545), using least square mean estimate.
In intermediate-risk patients (DIPSS Int-1 and Int-2), TSS was
reduced by 15.18 points at week 24, from 28.20 at baseline, in the
pelabresib and ruxolitinib treatment arm versus 12.74 points at
week 24, from 27.53 at baseline, in the placebo plus ruxolitinib
arm, which was significant (Δ -2.44, 95% CI [-4.48; -0.40],
p<0.02). DIPSS is an established prognostic system used to
predict patient survival, classifying myelofibrosis patients into
the following risk categories: low, intermediate-1, intermediate-2
or high.
Absolute change in TSS was included as a key secondary endpoint
to directly measure change in the average TSS from baseline to week
24. It is a continuous endpoint that provides a meaningful,
detailed assessment of symptom score reductions, thereby enhancing
precision in estimating the magnitude of symptom burden reduction
in patients with myelofibrosis. This endpoint was added to the
MANIFEST-2 clinical trial protocol following a Type C meeting with
the U.S. Food and Drug Administration (FDA) in September 2023.
TSS50, another key secondary endpoint, was achieved by 52% of
patients in the pelabresib and ruxolitinib treatment arm at week 24
compared with 46% in the placebo plus ruxolitinib arm (95% CI
[-3.5; 15.5], p=0.216). In intermediate-risk patients, TSS50 was
achieved by 55% of patients in the pelabresib and ruxolitinib
treatment arm at week 24 compared with 45% in the placebo plus
ruxolitinib arm (95% CI [0.35; 19.76], p<0.05).
“Myelofibrosis patients experience a severely diminished quality
of life due to symptoms such as severe fatigue, night sweats, bone
pain and fever – symptoms that can leave them bedridden for days
and with limited ability to participate in daily activities.
Reducing symptom burden is a primary goal of myelofibrosis
treatment,” said Ruben A. Mesa, M.D., FACP, President and Executive
Director, Atrium Health Levine Cancer Center and Atrium Health Wake
Forest Baptist Comprehensive Cancer Center. “Total symptom score
assessment is a validated tool to document the challenges that
patients encounter on a daily basis. The symptom reduction shown in
MANIFEST-2 is an important result that should be strongly
considered when evaluating the efficacy of the pelabresib and
ruxolitinib combination therapy for myelofibrosis.”
Improvements in Anemia
The MANIFEST-2 results show a greater proportion of patients
achieved hemoglobin response (≥ 1.5 g/dL from baseline) with the
pelabresib and ruxolitinib combination than with placebo and
ruxolitinib.
Pelabresib and Ruxolitinib Combination Was Well-Tolerated
At the time of this analysis, the safety of pelabresib and
ruxolitinib was consistent with the previously observed safety
profile of this combination therapy; no new safety signals were
observed. Importantly, adverse events of anemia were reported less
frequently with pelabresib and ruxolitinib than with placebo and
ruxolitinib.
ASH 2023 Annual Meeting Oral Presentation
Detailed findings of the Phase 3 MANIFEST-2 study will be
presented during an oral presentation, held on Sunday, December 10,
at 5:15 p.m. PST, at the 65th American Society for Hematology (ASH)
Annual Meeting and Exposition in San Diego, California. MorphoSys
will host an investor event with the company’s management team and
medical experts to review these data on Monday, December 11.
Planned Regulatory Next Steps
Based on the strong and comprehensive data generated from the
MANIFEST-2 study, MorphoSys will continue conversations with
regulatory agencies, with intention to submit a New Drug
Application for pelabresib in combination with ruxolitinib in
myelofibrosis to the FDA and a Marketing Authorization Application
to the European Medicines Agency in the middle of 2024. The
combination therapy received Fast Track designation for this
disease from the FDA in 2018.
Conference Call Details
MorphoSys management will host a conference call on Tuesday,
November 21, at 2:00 p.m. CET (1:00 p.m. GMT; 8:00 a.m. EST) to
review the Phase 3 MANIFEST-2 topline results.
Participants for the conference call and webcast may
pre-register and will receive dedicated dial-in details to easily
and quickly access the call:
https://services.choruscall.it/DiamondPassRegistration/register?confirmationNumber=8572124&linkSecurityString=11493ccf0c.
Please dial in 10 minutes before the beginning of the
conference.
The live webcast (audio and presentation) can be directly
accessed via
https://media.choruscall.eu/mediaframe/webcast.html?webcastid=jgAzP0ET
or via the Investors section under "Events & Conferences" on
MorphoSys' website, www.morphosys.com and after the call, a
slide-synchronized audio replay of the conference call will be
available at the same location.
About MorphoSys
At MorphoSys, we are driven by our mission: More life for people
with cancer. As a global commercial-stage biopharmaceutical
company, we develop and deliver innovative medicines, aspiring to
redefine how cancer is treated. MorphoSys is headquartered in
Planegg, Germany, and has its U.S. operations anchored in Boston,
Massachusetts. To learn more, visit us at www.morphosys.com and
follow us on Twitter at X and LinkedIn.
About Pelabresib
Pelabresib (CPI-0610) is an investigational selective small
molecule designed to promote anti-tumor activity by inhibiting the
function of bromodomain and extra-terminal domain (BET) proteins to
decrease the expression of abnormally expressed genes in cancer.
Pelabresib is being investigated as a treatment for myelofibrosis
and has not yet been approved by any regulatory authorities.
The development of pelabresib was funded in part by The Leukemia
and Lymphoma Society®.
About MANIFEST-2
MANIFEST-2 (NCT04603495) is a global, double-blind Phase 3
clinical trial that randomized 430 JAK inhibitor-naïve adult
patients with myelofibrosis 1:1 to receive pelabresib in
combination with ruxolitinib or placebo plus ruxolitinib. The
primary endpoint of the study is a 35% or greater reduction in
spleen volume (SVR35) from baseline at 24 weeks. The key secondary
endpoints of the study are the absolute change in total symptom
score (TSS) from baseline at 24 weeks and the proportion of
patients achieving a 50% or greater improvement in total symptom
score (TSS50) from baseline at 24 weeks. TSS is measured using the
myelofibrosis self-assessment form (MFSAF) v4.0, which asks
patients to report the severity of seven common symptoms, rating
each of them on a scale from 0 (absent) to 10 (worst
imaginable).
The new key secondary endpoint, absolute change in TSS, was
added to directly measure change in the average TSS from baseline
to week 24 of treatment and is listed as the first key secondary
endpoint in the MANIFEST-2 hierarchical testing scheme. The
decision to update the MANIFEST-2 clinical trial protocol was made
following a Type C meeting with the U.S. Food and Drug
Administration (FDA) in September 2023. The final clinical protocol
amendment is subject to approvals by health authorities outside of
the U.S.
Additional secondary endpoints include progression-free
survival, overall survival, duration of the splenic and total
symptom score response, and improvement in bone marrow fibrosis,
among others.
Constellation Pharmaceuticals, Inc., a MorphoSys company, is the
MANIFEST-2 trial sponsor.
About Myelofibrosis
Myelofibrosis, which belongs to a group of diseases called
myeloproliferative disorders, is a difficult-to-treat form of blood
cancer that’s characterized by bone marrow fibrosis (a buildup of
scar tissue in the bone marrow), spleen enlargement and anemia (low
red blood cell counts) often requiring periodic blood transfusions.
Patients with myelofibrosis can also suffer from a range of
physical symptoms, including severe fatigue, night sweats, itching,
increased bleeding and significant pain caused by their enlarged
spleen. For many living with myelofibrosis, the combination of
symptoms often severely impacts their quality of life. At
diagnosis, several factors, such as age, genetics and bloodwork,
help determine a patient’s long-term prognosis. About 90% of newly
diagnosed patients have intermediate- to high-risk disease, which
has a worse prognosis and a higher likelihood of disease-associated
symptoms. Today, myelofibrosis treatments revolve around the use of
medications called JAK inhibitors, which can improve spleen size,
anemia and general symptoms of myelofibrosis but do not address all
four hallmarks of the disease. Only about 50% of patients treated
with JAK inhibitors achieve adequate symptom control, and,
unfortunately, that relief fades with time for many. Patients
suffering from myelofibrosis are in critical need of new treatment
options.
Forward Looking Statements
This communication contains certain forward-looking statements
concerning the MorphoSys group of companies. The forward-looking
statements contained herein represent the judgment of MorphoSys as
of the date of this release and involve known and unknown risks and
uncertainties, which might cause the actual results, financial
condition and liquidity, performance or achievements of MorphoSys,
or industry results, to be materially different from any historic
or future results, financial conditions and liquidity, performance
or achievements expressed or implied by such forward-looking
statements. In addition, even if MorphoSys' results, performance,
financial condition and liquidity, and the development of the
industry in which it operates are consistent with such
forward-looking statements, they may not be predictive of results
or developments in future periods. Among the factors that may
result in differences are that MorphoSys' expectations may be
incorrect, the inherent uncertainties associated with competitive
developments, clinical trial and product development activities and
regulatory approval requirements, MorphoSys' reliance on
collaborations with third parties, estimating the commercial
potential of its development programs and other risks indicated in
the risk factors included in MorphoSys' Annual Report on Form 20-F
and other filings with the U.S. Securities and Exchange Commission.
Given these uncertainties, the reader is advised not to place any
undue reliance on such forward-looking statements. These
forward-looking statements speak only as of the date of publication
of this document. MorphoSys expressly disclaims any obligation to
update any such forward-looking statements in this document to
reflect any change in its expectations with regard thereto or any
change in events, conditions or circumstances on which any such
statement is based or that may affect the likelihood that actual
results will differ from those set forth in the forward-looking
statements, unless specifically required by law or regulation.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231120962550/en/
Media Contacts: Thomas Biegi Vice President Tel: +49
(0)151 / 74612318 thomas.biegi@morphosys.com Eamonn Nolan Director
Tel: +1 617-548-9271 eamonn.nolan@morphosys.com Investor
Contact: Dr. Julia Neugebauer Head of Investor Relations Tel:
+49 (0)89 / 899 27 179 julia.neugebauer@morphosys.com
MorphoSys (NASDAQ:MOR)
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