Press Release: Tolebrutinib designated Breakthrough Therapy by the
FDA for non-relapsing secondary progressive multiple sclerosis
Tolebrutinib designated Breakthrough Therapy by
the FDA for non-relapsing secondary progressive multiple
sclerosis
- Designation is based on positive
results from the HERCULES study in adults with non-relapsing
secondary progressive multiple sclerosis (nrSPMS)
- Tolebrutinib is the first and only
brain-penetrant BTK inhibitor in MS to be designated Breakthrough
Therapy by the FDA
Paris, December 13,
2024. The US Food and Drug Administration (FDA) has
granted Breakthrough Therapy designation to tolebrutinib for the
treatment of adults with non-relapsing secondary progressive
multiple sclerosis (nrSPMS). This is based on positive results from
the HERCULES phase 3 study, demonstrating that tolebrutinib delayed
the time to onset of 6-month confirmed disability progression
(CDP), by 31% compared to placebo (HR 0.69; 95% CI 0.55-0.88;
p=0.0026), with further analysis of secondary endpoints
demonstrating that the number of participants who experienced
confirmed disability improvement was nearly double with
tolebrutinib (10%) compared to those on placebo (5%) (HR 1.88; 95%
CI 1.10 to 3.21; nominal p=0.021).
FDA Breakthrough Therapy designation is designed to
expedite the development and review of medicines in the US that
target serious or life-threatening conditions. Medicines qualifying
for this designation must show preliminary clinical evidence that
the drug may demonstrate substantial improvement on clinically
significant endpoints over available medicines.
Erik Wallström, MD,
PhD
Global Head of Neurology Development, Sanofi
“This Breakthrough Therapy designation demonstrates the
potential for tolebrutinib to delay disability progression, a
critical unmet need for people living with multiple sclerosis. We
look forward to working with the FDA during the regulatory review
of this first of its kind medicine in non-relapsing secondary
progressive multiple sclerosis where there are currently no
approved treatments available.”
Liver enzyme elevations (>3xULN) were observed
in 4.1% of participants receiving tolebrutinib compared with 1.6%
in the placebo group. A small (0.5%) proportion of participants in
the tolebrutinib group experienced peak ALT increases of
>20xULN, all occurring within the first 90 days of treatment.
All but one case of liver enzyme elevations resolved without
further medical intervention. The implementation of more frequent
monitoring has helped mitigate serious liver sequelae.
Regulatory submissions of tolebrutinib are
currently being finalized for the US and prepared for the EU. As
with other medicines, Sanofi plans to confirm once a regulatory
submission for tolebrutinib has been accepted. The PERSEUS phase 3
study in primary progressive MS is currently ongoing with study
results anticipated in H2 2025.
Tolebrutinib is currently under clinical
investigation, and its safety and efficacy have not been evaluated
by any regulatory authority.
About multiple sclerosis
Multiple sclerosis is a chronic, immune-mediated, neurodegenerative
disease that may result in accumulation of irreversible
disabilities over time. The physical and cognitive disability
impairments translate into gradual deterioration of health status,
impacting patients’ care and quality of life. Disability
accumulation remains the significant unmet medical need in MS. To
date, the primary target of current medicines has been peripheral B
and T cells, while innate immunity, which is believed to drive
disability accumulation, remains largely unaddressed by current
medicines. Currently approved, or late-stage medicines being tested
for MS mainly target the adaptive immune system and/or do not act
directly within the central nervous system to drive clinical
benefit.
nrSPMS refers to people with MS who have stopped
experiencing relapses but continue to accumulate disability,
experienced as symptoms such as fatigue, cognitive impairment,
balance and gait impairment, loss of bowel and/or bladder function,
sexual disfunction, amongst others.
About tolebrutinib
Tolebrutinib is an investigational, oral, brain-penetrant, and
bioactive Bruton’s tyrosine kinase (BTK) inhibitor that achieves
cerebrospinal fluid concentrations predicted to modulate B
lymphocytes and disease-associated microglia. Tolebrutinib is being
evaluated in phase 3 clinical studies for the treatment of various
forms of multiple sclerosis and its safety and efficacy have not
been evaluated by any regulatory authority worldwide. For more
information on tolebrutinib clinical studies, please visit
www.clinicaltrials.gov.
About HERCULES
HERCULES (clinical study identifier: NCT04411641) was a
double-blind randomized phase 3 clinical study evaluating the
efficacy and safety of tolebrutinib in participants with nrSPMS.
nrSPMS was defined at baseline as having a SPMS diagnosis with an
expanded disability status scale (EDSS) between 3.0 and 6.5, no
clinical relapses for the previous 24 months and documented
evidence of disability accumulation in the previous 12 months.
Participants were randomized (2:1) to receive either an oral daily
dose of tolebrutinib or matching placebo for up to approximately 48
months.
The primary endpoint was 6-month CDP defined as the
increase of ≥1.0 point from the baseline EDSS score when the
baseline score is ≤5.0, or the increase of ≥0.5 point when the
baseline EDSS score was >5.0. Secondary endpoints included time
to onset of 3-month CDP as assessed by EDSS score, total number of
new or enlarging T2 hyperintense lesions as detected by MRI, time
to onset of confirmed disability improvement, 3-month change in 9
hole peg test and T25-FW test as well as the safety and
tolerability of tolebrutinib.
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 Relations
Sandrine Guendoul | + 33 6 25 09 14 25
| sandrine.guendoul@sanofi.com
Evan Berland | + 1 215 432 0234
| evan.berland@sanofi.com
Victor Rouault | + 33 6 70 93 71 40
| victor.rouault@sanofi.com
Timothy Gilbert |+ 1 516 521 2929
| timothy.gilbert@sanofi.com
Investor Relations
Thomas Kudsk Larsen |+ 44 7545 513 693
| thomas.larsen@sanofi.com
Alizé Kaisserian | + 33 6 47 04 12 11
| alize.kaisserian@sanofi.com
Felix Lauscher | + 1 908 612
7239 | felix.lauscher@sanofi.com
Keita Browne | + 1 781 249 1766
| keita.browne@sanofi.com
Nathalie Pham | + 33 7 85 93 30 17
| nathalie.pham@sanofi.com
Tarik Elgoutni | + 1 617 710 3587
| tarik.elgoutni@sanofi.com
Thibaud Châtelet | + 33 6 80 80 89 90
| thibaud.chatelet@sanofi.com
Sanofi forward-looking
statements
This press release contains forward-looking statements as defined
in the Private Securities Litigation Reform Act of 1995, as
amended. Forward-looking statements are statements that are not
historical facts. These statements include projections and
estimates and their underlying assumptions, statements regarding
plans, objectives, intentions, and expectations with respect to
future financial results, events, operations, services, product
development and potential, and statements regarding future
performance. Forward-looking statements are generally identified by
the words “expects”, “anticipates”, “believes”, “intends”,
“estimates”, “plans” and similar expressions. Although Sanofi’s
management believes that the expectations reflected in such
forward-looking statements are reasonable, investors are cautioned
that forward-looking information and statements are subject to
various risks and uncertainties, many of which are difficult to
predict and generally beyond the control of Sanofi, that could
cause actual results and developments to differ materially from
those expressed in, or implied or projected by, the forward-looking
information and statements. These risks and uncertainties include
among other things, the uncertainties inherent in research and
development, future clinical data and analysis, including post
marketing, decisions by regulatory authorities, such as the FDA or
the EMA, regarding whether and when to approve any drug, device or
biological application that may be filed for any such product
candidates as well as their decisions regarding labelling and other
matters that could affect the availability or commercial potential
of such product candidates, the fact that product candidates if
approved may not be commercially successful, the future approval
and commercial success of therapeutic alternatives, Sanofi’s
ability to benefit from external growth opportunities, to complete
related transactions and/or obtain regulatory clearances, risks
associated with intellectual property and any related pending or
future litigation and the ultimate outcome of such
litigation, trends in exchange rates and prevailing interest
rates, volatile economic and market conditions, cost containment
initiatives and subsequent changes thereto, and the impact that
pandemics or other global crises may have on us, our customers,
suppliers, vendors, and other business partners, and the financial
condition of any one of them, as well as on our employees and on
the global economy as a whole. The risks and uncertainties also
include the uncertainties discussed or identified in the public
filings with the SEC and the AMF made by Sanofi, including those
listed under “Risk Factors” and “Cautionary Statement Regarding
Forward-Looking Statements” in Sanofi’s annual report on Form 20-F
for the year ended December 31, 2023. Other than as required by
applicable law, Sanofi does not undertake any obligation to update
or revise any forward-looking information or statements.
All trademarks mentioned in this press release are
the property of the Sanofi group.
Grafico Azioni Sanofi (EU:SAN)
Storico
Da Nov 2024 a Dic 2024
Grafico Azioni Sanofi (EU:SAN)
Storico
Da Dic 2023 a Dic 2024
