Sanofi Reports Setbacks in Phase II Trials for Three Acquired Drug Candidates

Recently, Sanofi disclosed in its Q3 financial report that three newly acquired drugs encountered setbacks in Phase II clinical trials. These include the oral BTK inhibitor rilzabrutinib, which failed to meet the primary endpoint in a Phase II study for atopic dermatitis; Sanofi has decided to halt the development of RIPK1 inhibitor eclitasertib for cutaneous lupus erythematosus; the Phase II study of ICOS monoclonal antibody alomfilimab for treating solid tumors has also been terminated.

Rilzabrutinib is a covalent irreversible BTK inhibitor. In August 2020, Sanofi acquired three BTK inhibitors - rilzabrutinib, tolebrutinib, and atuzabrutinib - for $3.68 billion by acquiring Principia Biopharma.

In Q3 earnings report, Sanofi stated that the Phase II study of rilzabrutinib for the treatment of atopic dermatitis did not meet the primary endpoint (percentage change in EASI score at week 16), but other key clinical indicators showed significant improvement. Although progress in the atopic dermatitis field has been challenging, the Phase II study of rilzabrutinib for the treatment of moderate to severe chronic spontaneous urticaria successfully met the primary endpoint, and another Phase II study for the treatment of moderate to severe asthma is currently ongoing.

On the Road to BTK Inhibitor Development, Sanofi's Journey Has Been Quite Rocky. In 2021, the Phase III PEGASUS study of rilzabrutinib for the treatment of moderate to severe pemphigus delivered disappointing results. In 2022, due to several cases of drug-related liver injury, the Phase III studies of tolebrutinib for MS and myasthenia gravis were partially put on hold by the FDA. Subsequently, in its full-year 2022 financial report, Sanofi announced the discontinuation of the Phase III clinical trial of tolebrutinib for myasthenia gravis. In this year’s Q1 financial report, Sanofi ended the development of atuzabrutinib. Thus far, the three BTK inhibitors acquired by Sanofi from Principia have faced varying degrees of setbacks.

Eclitasertib (SAR443122) is a selective small molecule inhibitor of receptor-interacting serine/threonine-protein kinase 1 (RIPK1). RIPK1 is a key signaling protein in the tumor necrosis factor (TNF) receptor signaling pathway, regulating inflammation and cell death in tissues throughout the body. Studies have shown that increased RIPK1 activity in the brain drives neuroinflammation and programmed necrosis, and is associated with various central nervous system (CNS) and peripheral diseases.

In October 2018, Sanofi and Denali entered into a global development and commercialization collaboration for two RIPK1 inhibitors, eclitasertib and SAR443820 (DNL788). Under the terms of the agreement, Sanofi will pay Denali an upfront payment of $125 million, as well as potential development and promotion milestone payments exceeding $1 billion in the future. Sanofi will fully fund the clinical development of eclitasertib for systemic inflammatory diseases.

Based on the efficacy results from the Phase II proof-of-concept study, Sanofi has decided to discontinue the development of eclitasertib for cutaneous lupus erythematosus. Sanofi stated that eclitasertib was generally well-tolerated and is currently undergoing a Phase II study for ulcerative colitis.

Alomfilimab is an ICOS monoclonal antibody. In January 2021, Sanofi acquired Kymab, gaining a series of pipeline products including alomfilimab. This time, Sanofi stated that the decision to terminate the Phase II study of alomfilimab for treating solid tumors was not based on any safety signals.

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