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, PhDGlobal
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 sclerosisMultiple 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 tolebrutinibTolebrutinib 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 HERCULESHERCULES (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 RelationsSandrine
Guendoul | + 33 6 25 09 14 25
| sandrine.guendoul@sanofi.comEvan
Berland | + 1 215 432 0234
| evan.berland@sanofi.comVictor
Rouault | + 33 6 70 93 71 40
| victor.rouault@sanofi.comTimothy Gilbert |+
1 516 521 2929 | timothy.gilbert@sanofi.com
Investor RelationsThomas Kudsk
Larsen |+ 44 7545 513 693
| thomas.larsen@sanofi.comAlizé
Kaisserian | + 33 6 47 04 12 11
| alize.kaisserian@sanofi.comFelix
Lauscher | + 1 908 612 7239
| felix.lauscher@sanofi.comKeita
Browne | + 1 781 249 1766
| keita.browne@sanofi.comNathalie
Pham | + 33 7 85 93 30 17
| nathalie.pham@sanofi.comTarik
Elgoutni | + 1 617 710 3587
| tarik.elgoutni@sanofi.comThibaud
Châtelet | + 33 6 80 80 89 90
| thibaud.chatelet@sanofi.com
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