Paris, May 22, 2024. Encouraging results from a phase 2 study showed that treatment with oral rilzabrutinib at both high dose and low doses led to a numerical reduction in loss of asthma control (LOAC) events (the primary endpoint) and improvements in symptoms in adult patients with uncontrolled moderate-to-severe asthma. These results were presented today as a late-breaking poster at the 2024 American Thoracic Society (ATS) International Conference in San Diego and will support the phase 3 program where a twice-daily dose of rilzabrutinib will be studied for moderate-to-severe asthma.

Asthma is one of the most common chronic respiratory diseases affecting millions of people worldwide. Despite standard-of-care treatment, about 50% of patients with asthma remain uncontrolled with a high symptom burden that impacts their quality of life.

Tanya M. Laidlaw, MD
Director of Translational Research in Allergy Brigham and Women's Hospital, Boston, MA
“Many of my patients with asthma who are treated with standard of care inhaled therapies, even those with infrequent asthma attacks, still suffer from asthma symptoms and their activities are limited because of it. These patients may not qualify for a biologic medicine today but could benefit from an oral therapy that intervenes earlier in the disease. These results are encouraging as they show an improvement in asthma symptoms and a numerical reduction in Loss of Asthma Control events – important parameters in the treatment of this chronic respiratory condition that can significantly impact our patients’ daily lives.”

In this proof-of-concept study, treatment with high and low dose rilzabrutinib resulted in a 36% [OR: 0.584 (0.253, 1.349)] and 25% [OR:0.570 (0.202, 1.608)] relative risk reduction in loss of asthma control (LOAC) events, respectively, at week 12 (primary endpoint). Nominally significant and clinically meaningful improvements in asthma symptoms were also observed with a -0.54/-0.59 LS mean difference in asthma control questionnaire, ACQ-5. Improvements in ACQ-5 were seen as early as week 2.

Rilzabrutinib high and low doses were well tolerated over 12 weeks of treatment with no events of cytopenia, hemorrhagic events, or atrial fibrillation and no imbalance in liver function tests. Treatment-emergent adverse events (TEAEs) occurring with higher frequency with rilzabrutinib versus placebo were diarrhea (10.9% and 9.4% with rilzabrutinib high and low dose, versus 0% and 3.1% with matching placebo, respectively).

Houman Ashrafian
Executive Vice President, Head of Research and Development, Sanofi
“We are incredibly encouraged by the reduction in loss of asthma control events and improvements in asthma symptoms and look forward to advancing rilzabrutinib into a broader phase 3 clinical development program to further explore its potential in this disease. Advanced oral therapies have the potential to change the treatment paradigm for diseases like asthma, and we remain committed to exploring disruptive mechanisms of action for people living with uncontrolled chronic inflammatory diseases.”

Rilzabrutinib is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority.

About the study
This phase 2 study is a randomized, double-blind, placebo-controlled, parallel-group, 12-week proof-of-concept study to assess the efficacy, safety, and tolerability of rilzabrutinib in participants with moderate-to-severe asthma who are not well controlled on inhaled corticosteroid (ICS) plus long-acting β2 adrenergic agonist (LABA) therapy. Two doses of rilzabrutinib, 800 mg daily and 1200 mg daily, were studied. Patients were randomized 1:1 to receive either rilzabrutinib or placebo to be added to a background therapy of ICS/LABA which was withdrawn during the 12-week treatment period.

The primary endpoint was reduction in LOAC events. Secondary endpoints included asthma control (measured by the asthma control questionnaire, ACQ-5) and asthma quality of life (measured by the asthma quality of life questionnaire, AQLQ) or lung function (measured by FEV1).

About rilzabrutinib
Rilzabrutinib is an oral, reversible, covalent BTK inhibitor that has the potential to be a first- and/or best-in-class treatment for several immune-mediated diseases. BTK, expressed in B cells and mast cells, plays a critical role in multiple immune-mediated disease processes. With the application of Sanofi’s TAILORED COVALENCY^® technology, rilzabrutinib can selectively inhibit the BTK target while potentially reducing the risk of off-target side effects.

Rilzabrutinib is being studied across a variety of immune-mediated diseases, including immune thrombocytopenia (ITP), asthma, chronic spontaneous urticaria, prurigo nodularis, IgG4-related disease, and warm autoimmune hemolytic anemia.

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
Nicolas Obrist | + 33 6 77 21 27 55 | nicolas.obrist@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
Arnaud Delépine | + 33 6 73 69 36 93 | arnaud.delepine@sanofi.com
Corentine Driancourt | + 33 6 40 56 92 21 | corentine.driancourt@sanofi.com
Felix Lauscher | + 1 908 612 7239 | felix.lauscher@sanofi.com
Tarik Elgoutni| + 1 617 710 3587 | tarik.elgoutni@sanofi.com
Nathalie Pham | + 33 7 85 93 30 17 | nathalie.pham@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. 

Source:- Globenewswire