Dive Brief:

• An experimental Sanofi medicine failed two studies in multiple sclerosis but met its main objective in a third trial in a less common form of the disease, the company said Monday.
• In two Phase 3 studies of people with relapsing forms of MS, the drug tolebrutinib wasn’t better than another Sanofi medicine, Aubagio, at reducing the rate of disease flare-ups. But tolebrutinib did meaningfully delay the onset of disability progression in people with “non-relapsing secondary progressive” MS in a separate late-stage trial, and showed a similar effect in the other two trials as well, Sanofi said.
• Sanofi only provided summary results. Specific data will be presented at a medical meeting later this month. But the company did say the findings will form the basis of discussions with drug regulators. A Phase 3 trial is also underway in primary progressive MS, for which success depends on tolebrutinib’s ability to delay disability progression. Results are expected next year.

Dive Insight:

Analysts and investors have dialed back their expectations for tolebrutinib since Sanofi bought its developer, Principia Biopharma, four years ago.

The drug is part of a newer generation of would-be MS medications called BTK inhibitors that, unlike their cancer-fighting predecessors, are designed to get into the brain and treat autoimmune conditions. However, study results so far have been underwhelming. Safety concerns slowed the progress of multiple programs, including tolebrutinib, while Merck KGaA’s evobrutinib failed a pair of Phase 3 tests last December.

Ahead of Sanofi’s readout, many investors “anticipated negative tolebrutinib news,” wrote Leerink Partners analyst David Risinger on Tuesday. Its studies in relapsing MS were designed similarly to Merck KGaA’s trials and, even if the results had been positive, tolebrutinib would eventually have had to compete with several effective and convenient medicines, added Stifel’s Eric Le Berrigaud in a separate client note.

Yet, by claiming success in non-relapsing secondary progressive MS, or nrSPMS, Sanofi may have a chance to make something of tolebrutinib. The condition is different from relapsing MS in that people accumulate disabilities over time, instead of experiencing periodic disease flares. There are also no therapies specifically approved to treat it, meaning tolebrutinib become “a referenced drug” for the disease, “if not the standard of care,” wrote Le Berrigaud. He estimates tolebrutinib still holds the potential to be a blockbuster medicine, with a market opportunity of about $3 billion to $3.5 billion in the U.S. alone.

Even at that figure, tolebrutinib’s sales potential would be lower than what Sanofi once envisioned. The company believes about 170,000 people are currently diagnosed with nrSPMS in the U.S. and Europe, far fewer than the 910,000 Sanofi has estimated to have relapsing MS.

Additionally, Sanofi hasn’t disclosed important information from the tolebrutinib trial, like how much the drug benefited patients or whether it caused liver-related side effects that have occurred in testing of BTK blockers for MS. A preliminary analysis of liver safety was “consistent with previous tolebrutinib studies,” Sanofi said in its statement.

Leerink’s Risinger also noted how, even if tolebrutinib is approved, insurers may limit access in nrSPMS and prioritize off-label use of other MS drugs since it couldn’t outperform Aubagio.

Further competition could be coming, too. Roche and Novartis have BTK inhibitors in advanced testing for MS, with results coming in the next couple of years, according to a federal database.