ASH: Sarclisa combinations demonstrated significant
benefits in newly diagnosed multiple myeloma patients
- New analysis from the IMROZ phase 3
study of Sarclisa-VRd demonstrated higher and sustained MRD
negativity rates in transplant-ineligible NDMM patients versus VRd
alone
- New detailed results from the
GMMG-HD7 phase 3 study of Sarclisa-RVd induction therapy resulted
in a significant and clinically meaningful PFS benefit with deeper
MRD negativity in transplant-eligible NDMM patients
- Results support the benefit of
Sarclisa-based combinations to patients in the front-line setting
and the ongoing use of MRD negativity as a potential surrogate
endpoint for PFS in MM research
Paris, December 9, 2024. New
data from three oral presentations, which demonstrated significant
clinical benefit with Sarclisa-based quadruplets in newly diagnosed
multiple myeloma (NDMM) patients were featured at the 66th American
Society of Hematology (ASH) Annual Meeting & Exposition in San
Diego, CA, US. The presentations, including results from the IMROZ
and German-speaking Myeloma Multicenter Group (GMMG)-HD7 phase 3
studies, showcased deep and durable responses and improved
long-term outcomes with Sarclisa when added to current
standard-of-care NDMM regimens.
Dietmar Berger, MD, PhD Chief
Medical Officer, Global Head of Development at Sanofi“An important
part of our approach to scientific innovation in oncology is
identifying synergistic combinations, which may allow us to impact
numerous unmet needs with a single therapy and expand the pool of
patients who could one day benefit from our medicines. Results from
key studies evaluating Sarclisa combinations further reinforce our
confidence in this strategy and speak to the potential benefit of
Sarclisa as a backbone therapy for newly diagnosed multiple
myeloma, regardless of transplant eligibility.”
Additional IMROZ phase 3 study analysis
evaluating MRD in transplant-ineligible (TI) NDMM patientsThe IMROZ
phase 3 study demonstrated that Sarclisa in combination with
standard-of-care bortezomib, lenalidomide and dexamethasone (VRd),
followed by Sarclisa-Rd, improved progression-free survival (PFS)
and led to a rapid and greater depth of response compared to VRd
alone, as shown by minimal residual disease (MRD) negativity rate
over time, in TI NDMM patients. MRD negativity represents a measure
of malignant cells left in the bone marrow after treatment and has
been increasingly used as a surrogate endpoint for PFS in MM
research. Numerous independent studies have shown a correlation
between MRD negativity, deeper treatment responses and improved
long-term outcomes.
Sarclisa-VRd demonstrated a consistent benefit
at every time point up to 60 months and led to the highest MRD
negativity rate of a NDMM regimen with a VRd backbone, when
evaluating exclusively TI patients.
- Higher MRD
negativity rates were observed at both the end of initiation and
during maintenance, with 58.1% of patients in the
intention-to-treat (ITT) population treated with Sarclisa-VRd
achieving MRD negativity versus 43.6% of patients in the
control arm (OR 1.79; 95% CI: 1.22 to 2.63; p=0.0014).
-
In addition, patients treated with Sarclisa-VRd were significantly
less likely to lose MRD negativity status post-induction, with
only 12.3% of patients converting to MRD-positive status
during maintenance (at 36 months), compared to 34.8% of
patients in the control arm.
- Sustained MRD negativity
rates at ≥24 and ≥36 months were also two-to-threefold higher with
Sarclisa-VRd compared to VRd (35.8% vs 13.3% and 25.7% vs
7.2%, respectively) at 10-5 sensitivity threshold, with higher
rates also observed in the experimental arm at 10-6 sensitivity
threshold. The deep responses observed with Sarclisa-VRd ultimately
translated into an early PFS benefit that was maintained over
time.
- The safety and tolerability of
Sarclisa observed in this study was consistent with the established
safety profile of Sarclisa and VRd with no new safety signals
observed.
Robert Orlowski, MD, PhD
Florence Maude Thomas Cancer Research Professor at The University
of Texas MD Anderson Cancer Center“MRD negativity has long been
used to infer deeper responses and improved outcomes in multiple
myeloma research, but few studies have evaluated sustained MRD
negativity beyond one year. In the latest analysis from the IMROZ
study, one of the longest to evaluate MRD negativity with a
CD38-based quadruplet, newly diagnosed transplant-ineligible
patients treated with isatuximab-VRd were more likely to achieve
this threshold compared to those receiving VRd alone and maintain
it as long as three years. When viewed in tandem with earlier
findings highlighting the significant progression-free survival
benefit from IMROZ, these data reinforce the potential of
isatuximab to generate deep and durable improvements in clinical
outcomes throughout treatment when added to the standard-of-care
regimen.”
New key results from the GMMG-HD7 study in
transplant-eligible (TE) NDMMNew data from the induction part of
the GMMG-HD7 phase 3 study were featured across two oral
presentations at ASH. GMMG-HD7 is an investigational, pivotal,
randomized, open-label, multicenter, 2-part phase 3 study
evaluating Sarclisa in combination with RVd versus RVd induction
followed by post-transplant re-randomization to Sarclisa plus
lenalidomide versus lenalidomide maintenance in TE NDMM patients.
The following results, which were simultaneously published in the
Journal of Clinical Oncology, were reported for Sarclisa-RVd
compared to RVd in the first part:
- Higher MRD
negativity rates were observed at the end of initiation (18 weeks)
as assessed as a primary endpoint, with 50.1% of patients
in the ITT population treated with Sarclisa-RVd achieving MRD
negativity versus 35.6% of patients in the control arm (OR
1.83; 95% CI: 1.34 to 2.51; p<0.001).
- 30% reduction in the risk
of disease progression or death observed at a median
follow-up of 47 months from first randomization in patients treated
with Sarclisa-RVd during induction, regardless of the maintenance
therapy received (HR 0.70; 95% CI 0.52-0.95; stratified log-rank
p=0.0184).
- Three-year PFS rates in the
Sarclisa-RVd arm were 83% compared to 75% in the control
arm.
- Additionally, 53.1% of
patients receiving Sarclisa-RVd experienced continued MRD
negativity (compared to 38% in the control arm), defined
as MRD negativity persisting from post-induction to
post-transplant, which was consistent with a prolonged PFS benefit
(OR 1.84; 95% CI: 1.28-2.63; p=0.0008).
The safety and tolerability in this study were
consistent with the established safety profile of Sarclisa and RVd
with no new safety signals observed.
GMMG-HD7 is the first and only phase 3 study to
demonstrate a deep and rapid response with an anti-CD38-based
induction regimen in TE NDMM patients, regardless of maintenance
therapy, alongside a statistically significant MRD negativity
benefit post-induction, without consolidation. Additionally, the
data showed the highest post-induction and post-transplant MRD
negativity rates of any CD38 monoclonal antibody using RVd as a
backbone in TE NDMM. The results add to the growing body of
clinical evidence supporting the use of Sarclisa in the front-line
setting.
Hartmut Goldschmidt,
MDPresident of GMMG, Professor of Medicine at the
Heidelberg University Hospital (UKHD), Germany and principal
investigator of the study“Successful induction therapy prior to
autologous stem cell transplant is critical to achieving optimal
outcomes in front-line multiple myeloma treatment. In the GMMG-HD7
study, we observed a significant and sustained progression-free
survival benefit when adding isatuximab to the current
standard-of-care induction regimen, reinforcing the potential of
this quadruplet when used prior to transplant, regardless of the
maintenance therapy.”
Advancing Sarclisa combinations in hematologic
malignanciesA fourth oral presentation at ASH featured interim
results from the investigational ISAMYP phase 2 study in AL
amyloidosis, another rare disease. Results showed the addition of
Sarclisa to pomalidomide, and dexamethasone (Pd) resulted in rapid
hematological responses in patients with relapsed AL amyloidosis,
who experienced suboptimal response to previous therapy or at
relapse. AL amyloidosis is a rare plasma cell disorder associated
with particularly poor outcomes in the later stages of the disease.
Although recent treatment advancements have helped improve outcomes
for certain patient segments, unmet needs continue to exist,
particularly for frail or TI populations.
The safety and efficacy of Sarclisa in
combination with Pd for AL amyloidosis has not been evaluated by
any regulatory authority.
About the IMROZ studyThe randomized,
multi-center, open label IMROZ phase 3 study enrolled 446 patients
with TI NDMM across 21 countries and 96 centers. During the study,
Sarclisa was administered through an intravenous infusion at a dose
of 10 mg/kg once weekly for five weeks during first 42-day cycle
and once every two weeks in cycles 2 to 4 in combination with
subcutaneous bortezomib, oral lenalidomide and intravenous or oral
dexamethasone. Then Sarclisa was administered every 2 weeks from
cycle 5 to 17 and every 4 weeks in cycles 18+ during 28-day cycles
in combination with lenalidomide and dexamethasone at the standard
dose, until disease progression, unacceptable toxicity, or
patient’s decision to stop the study treatment. The primary
endpoint of IMROZ is PFS. Key secondary endpoints include complete
response rate, MRD negativity rate for patients with a complete
response, very good partial response or better rate, and overall
survival. Other secondary endpoints are overall response rate, time
to progression, duration of response, time to first response, time
to best response, PFS on next line of therapy, PFS by MRD status,
sustained MRD negativity greater than or equal to 12 months rate,
safety, pharmacokinetic profile, immunogenicity, disease-specific
and generic health-related quality of life, disease and
treatment-related symptoms, health state utility, and health
status.
In September 2024, Sarclisa was approved in the
US in combination with VRd as a front-line treatment option for
adult patients with NDMM who are not eligible for ASCT, based on
results from the IMROZ phase 3 study. In November 2024, the
European Medicines Agency (EMA)’s Committee for Medicinal Products
for Human Use (CHMP) adopted a positive opinion recommending the
approval of Sarclisa-VRd for the treatment of adult patients with
NDMM who are ineligible for ASCT. Additionally, applications for
this indication are currently under regulatory review in Japan and
China.
About the GMMG-HD7 studyGMMG-HD7 is an
investigational, pivotal, randomized, open-label, multicenter,
2-part phase 3 study evaluating Sarclisa in combination with RVd
versus RVd induction followed by post-transplant re-randomization
to Sarclisa plus lenalidomide versus lenalidomide maintenance in TE
NDMM patients. The GMMG-initiated study is being conducted in close
collaboration with Sanofi based on jointly defined research. Sanofi
provided financial support to GMMG for this study. In December
2021, Sanofi and GMMG shared results from part one, which met the
primary endpoint of MRD negativity after induction therapy and
before transplant in NDMM patients.
The study enrolled 662 patients with TE NDMM
across 67 sites in Germany. In the first part of the study, all
participants were equally randomized to receive three 42-day cycles
of RVd in both arms of the study, while Sarclisa was added to only
one study arm. In the second part of the study, patients were
re-randomized post-transplant to receive Sarclisa plus lenalidomide
or lenalidomide alone as maintenance therapy. During the study,
Sarclisa was administered through an intravenous infusion at a dose
of 10 mg/kg once weekly for the first four weeks of cycle one, then
every other week for the rest of the induction period.
MRD negativity was assessed by next-generation
flow cytometry (sensitivity of 1x10-5) after induction. In the
latest readout of the study, PFS for both Sarclisa plus RVd as an
induction therapy, regardless of maintenance treatment, and
Sarclisa plus lenalidomide as a maintenance regimen were measured
from first randomization.
GMMG-HD7 protocol defined the primary endpoints
of MRD negativity after induction treatment for the first part of
the study, and PFS following the second randomization after
transplant for part two of the study, in which Sarclisa was added
to lenalidomide maintenance, with the latter primary endpoint
anticipated to be available later. The key secondary endpoint for
the first part of the study was PFS from first randomization.
Additional secondary endpoints included rates of complete response
after induction, and intensification, overall survival, and
safety.
The use of Sarclisa in combination with RVd is
investigational and has not been evaluated by any regulatory
authority. Submission of an application for this combination in the
EU is anticipated in the coming months.
About SarclisaSarclisa (isatuximab) is a CD38
monoclonal antibody that binds to a specific epitope on the CD38
receptor on MM cells, inducing distinct antitumor activity. It is
designed to work through multiple mechanisms of action including
programmed tumor cell death (apoptosis) and immunomodulatory
activity. CD38 is highly and uniformly expressed on the surface of
MM cells, making it a target for antibody-based therapeutics such
as Sarclisa. In the US, the non-proprietary name for Sarclisa is
isatuximab-irfc, with irfc as the suffix designated in accordance
with nonproprietary naming of biological products guidance for
industry issued by the US FDA.
Currently Sarclisa is approved in more than 50
countries, including the US and EU, across two indications;
Sarclisa is approved under an additional indication in the US.
Based on the ICARIA-MM phase 3 study, Sarclisa is approved in
combination with Pd for the treatment of patients with relapsed
refractory MM (R/R MM) who have received ≥2 prior therapies,
including lenalidomide and a proteasome inhibitor and who
progressed on last therapy. Based on the IKEMA phase 3 study,
Sarclisa is also approved in 50 countries in combination with
carfilzomib and dexamethasone, including in the US for the
treatment of patients with R/R MM who have received 1–3 prior lines
of therapy and in the EU for patients with MM who have received at
least 1 prior therapy. In the US, Sarclisa is approved in
combination with VRd as a front-line treatment option for adult
patients with NDMM who are not eligible for ASCT, based on the
IMROZ phase 3 study. On November 14, 2024, the European Medicines
Agency (EMA)’s Committee for Medicinal Products for Human Use
(CHMP) adopted a positive opinion recommending the approval of
Sarclisa-VRd in this patient population. A final decision is
expected in the coming months.
Sanofi continues to advance Sarclisa as part of
a patient-centric clinical development program, which includes
several phase 2 and phase 3 studies across the MM treatment
continuum spanning six potential indications. In addition, the
company is evaluating a subcutaneous administration method for
Sarclisa in clinical studies. The safety and efficacy of Sarclisa
has not been evaluated by any regulatory authority outside of its
approved indications and methods of delivery.
In striving to become the number one
immunoscience company globally, Sanofi remains committed to
advancing oncology innovation. Through focused strategic decisions
the company has reshaped and prioritized its pipeline, leveraging
its expertise in immunoscience to drive progress. Efforts are
centered on difficult-to-treat often rare cancers such as select
hematologic malignancies and solid tumors with critical unmet
needs, including multiple myeloma, acute myeloid leukemia, certain
types of lymphomas, as well as gastrointestinal and lung
cancers.
For more information on Sarclisa clinical
studies, please visit www.clinicaltrials.gov.
About the German-speaking Myeloma Multicenter
Group (GMMG)GMMG is the largest study group focusing on MM in
Germany, with headquarters based in Heidelberg. Within the last 20+
years, the GMMG study group has performed numerous studies
including five randomized, multicenter phase 3 studies with 4,000
patients enrolled from about 90 participating and co-treating
centers throughout Germany. The overall goal of GMMG is to generate
improved therapies for myeloma patients through the development and
testing of novel and personalized, genome- and signaling-driven
treatment strategies. The GMMG has set itself the goal of achieving
further approvals for effective antibody-based drug combinations
for the first-line treatment of myeloma patients, in which
antibody-based treatment regimens have been integrated into seven
GMMG study concepts (CONCEPT, DANTE, DADA, HD6, HD7, HD8, HD9 and
HD10).
About Sanofi We are an innovative global healthcare
company, driven by one purpose: we chase the miracles of science to
improve people’s lives. Our team, across the world, is dedicated to
transforming the practice of medicine by working to turn the
impossible into the possible. We provide potentially life-changing
treatment options and life-saving vaccine protection to millions of
people globally, while putting sustainability and social
responsibility at the center of our ambitions.Sanofi is listed on
EURONEXT: SAN and NASDAQ: SNY
Media RelationsSandrine
Guendoul | +33 6 25 09 14 25
| sandrine.guendoul@sanofi.comEvan Berland |
+1 215 432 0234 | evan.berland@sanofi.com Nicolas
Obrist | +33 6 77 21 27 55 |
nicolas.obrist@sanofi.com Léo Le Bourhis | + 33 6
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Rouault | +33 6 70 93 71 40
| victor.rouault@sanofi.comTimothy
Gilbert | +1 516 521 2929 |
timothy.gilbert@sanofi.com
Investor RelationsThomas Kudsk
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