Tolebrutinib

Sanofi is to supplement its vaccine offering with the acquisition of Dynavax Technologies for $2.2 billion in cash, the companies said Wednesday. The deal is the French drugmaker’s largest since it bought Blueprint Medicines for $9.1 billion in June. Dynavax sells an adult hepatitis B vaccine, Heplisav-B, which brought in $90 million in the third quarter of 2025. The California biotech has previously said it expects full-year 2025 revenues of $315 million to $325 million for the shot. According to Sanofi, Heplisav-B has an advantage over GSK’s established drug in its dosing regimen. Two shots of Heplisav-B are given over one month, whereas Shingrix requires a second dose to be given two to six months after the first, or one to two months later in immunodeficient or immunosuppressed people. Heplisav-B can therefore provide seroprotection faster than other hepatitis B vaccines, Sanofi said. The vaccine combines the hepatitis B surface antigen with an adjuvant developed by Dynavax. This is a toll-like receptor 9 agonist, designed to boost the recipient’s immune response. Like Shingrix, it is an intramuscular shot. Dynavax also has an investigational shingles vaccine, and said in August that early Phase 1/2 data suggest the program, called Z-1018, has “comparable immunogenicity” to GSK’s market-leading Shingrix, with more benign safety. The biotech also has experimental vaccines for plague and pandemic influenza in Phase 2, according to its website. It is partnered with the US Department of Defense on the plague vaccine. In November Dynavax licensed Vaxart’s oral Covid-19 vaccine. Vaxart will receive a $25 million upfront fee for the Phase 2-stage pill, and Dynavax will also invest $5 million into the company. It will also hand over $50 million if it wants to push the vaccine into Phase 3. Fourth buy this year Sanofi said the $15.50-per-share offer would not affect its financial guidance for 2025. It expects the deal to close in the first quarter of 2026. Sanofi has bought several companies this year. As well as the deal for Blueprint — which would not have happened were it not for a dinner meeting in Paris in April — it spent $470 million on Vigil Neuroscience, which has a pill for Alzheimer’s disease in Phase 2. It also acquired UK vaccine startup ViceBio in July, for $1.2 billion upfront. The deals are partly aimed at decreasing Sanofi’s reliance on its immunological blockbuster Dupixent, which faces possible patent expiry in 2030. FDA knockback Less positively, the FDA kicked Sanofi’s approval application for its multiple sclerosis candidate tolebrutinib into the long grass. The agency issued a complete response letter for the BTK inhibitor, according to a Wednesday release . Sanofi was seeking approval in adults with non-relapsing secondary progressive MS. On Dec. 15 Sanofi said that the FDA had delayed a decision on this point beyond tolebrutinib’s PDUFA date of Dec. 28. It added that it expected further guidance from the agency on when a decision might come in the first quarter of 2026. But the decision seems to have come within the original timeframe after all. “Today’s FDA decision is a significant and meaningful change in direction from the feedback the agency previously provided to Sanofi. We are very disappointed by the FDA’s action,” said Sanofi R&D chief Houman Ashrafian. The company plans to working with the FDA to find a path forward for tolebrutinib, Ashrafian added.

Sanofi’s recent string of bad luck with tolebrutinib continues, with the company announcing Wednesday that the FDA declined to approve its application seeking approval of the oral brain-penetrant BTK inhibitor to treat non-relapsing secondary progressive multiple sclerosis (nrSPMS) in adults.Just last week, the French drugmaker said the FDA had delayed the target action date for the investigational drug in nrSPMS a second time, following an earlier postponement from Sep. 28 to Dec. 28.Houman Ashrafian, R&D head at Sanofi, said the complete response letter from the FDA was disappointing, what he describes as a "significant and meaningful change in direction from the feedback the agency previously provided.” The company was anticipating further guidance by the end of the first quarter next year after submitting an expanded access protocol for tolebrutinib’s nrSPMS indication at the US regulator’s request.“We believe that the FDA should also take the advice of scientific experts, clinicians, and patients in this matter to ensure all perspectives are considered,” Ashrafian noted, emphasising that “disability progression remains a large unmet medical need in MS.”Sanofi further stated it is performing an impairment test on the intangible asset value of tolebrutinib, with results due in January. However, the company clarified the outcomes are unlikely to have an impact on its net income, earnings per share or 2025 guidance. The therapy continues to be reviewed in the EU or nrSPMS, and also secured provisional approval in the United Arab Emirates for the same earlier this year.Meanwhile, also last week, a pivotal study of the Sanofi drug in primary progressive MS missed its primary endpoint of delaying disability progression, leading the company to drop plans of seeking approval for the indication.