EU regulators approve tolebrutinib, now Cenrifki, for nonreplapsing SPMS
Decision comes just months after FDA rejection of Sanofi's oral therapy
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European Union regulators are charged with approving new medications for all EU member nations. (Photo from iStock)
- Tolebrutinib has been approved in the European Union, under the brand name Cenrifki, to treat nonrelapsing secondary progressive multiple sclerosis.
- It is the first EU treatment specifically targeting disability progression in people with SPMS with no relapses.
- The approval by EU regulators comes just months after the U.S. FDA rejected the Sanofi oral therapy.
Tolebrutinib has been approved in the European Union for the treatment of secondary progressive multiple sclerosis (SPMS) for people who have not experienced a relapse in the previous two years. The medication will be sold under the brand name Cenrifki.
The decision, which is in line with a positive opinion issued by a European Medicines Agency committee earlier this year, makes tolebrutinib the first treatment approved in the EU that targets disability progression in nonrelapsing SPMS.
The medication will be made commercially available in Germany this year, “in close collaboration between local medical teams, treating MS specialists and … patients,” according to a press release from the drug’s developer, Sanofi. Treated individuals will have access to a “robust” patient support, as well as the “required Risk Management Program.”
“Cenrifki represents a significant advancement for people living with SPMS by targeting disability progression,” Sanofi stated.
Tolebrutinib is also cleared in the United Arab Emirates to treat people with nonrelapsing MS, and to slow disability accumulation independent of relapse activity in adults with MS.
U.S. regulators, however, declined to approve the therapy late last year, citing insufficient evidence of efficacy along with safety concerns related to severe liver injury risks.
Most people with multiple sclerosis (MS) first experience a relapsing-remitting disease course, when the condition is known as RRMS. In RRMS, periods of symptom worsening, or relapses, are followed by periods in which symptoms stabilize or ease. Some people with RRMS will eventually transition to SPMS, in which symptoms gradually worsen over time, regardless of relapse activity.
People with SPMS who continue to experience some relapses can benefit from the more than 20 disease-modifying therapies that are used for RRMS.
Tolebrutinib designed to slow progressing disability in SPMS
However, treatments for slowing disease progression in SPMS without relapses are lacking, and disability often progresses unchecked, according to researchers.
“Addressing disability progression remains one of the most significant unmet needs in MS care,” Sanofi noted in the press release. According to the company, the annual cost of MS-related disability in major European economies surpasses the average income a person makes in a year. Many people also face a loss of income when disability impairs their ability to work.
The processes underlying the inflammatory flare-ups linked to relapses are thought to be different than those that drive the chronic, smoldering inflammation that contributes to neurodegeneration and disability progression. As such, nonrelapsing MS needs a different therapeutic approach, scientists say.
Tolebrutinib is a daily oral therapy designed to inhibit Bruton tyrosine kinase (BTK), an enzyme involved in the activation of immune cells thought to contribute to both acute and smoldering inflammation in MS.
The EU approval for the drug was mainly supported by data from the Phase 3 HERCULES trial (NCT04411641), which showed that tolebrutinib significantly reduced the risk of confirmed disability progression in people with nonrelapsing SPMS relative to a placebo.
Supportive data came from the twin Phase 3 GEMINI 1 (NCT04410978) and GEMINI 2 (NCT04410991) studies, which involved people with relapsing forms of MS. While the studies failed to meet their primary goal of demonstrating that tolebrutinib was better at lowering relapse rates than the approved therapy Aubagio (teriflunomide), the treatment again showed an ability to reduce the risk of confirmed disability worsening.
Liver monitoring will be required for patients
Across clinical trials, the safety profile of tolebrutinib has been consistent, according to Sanofi, with COVID-19 and upper respiratory tract infections as the most common side effects.
Still, the medication can also cause significant elevations in liver enzymes, a potential precursor to more serious liver injury. For this reason, all patients must be enrolled in a risk management program before initiating tolebrutinib, through which they will be required to strictly adhere to liver monitoring requirements.
Sanofi was previously also developing tolebrutinib for primary progressive multiple sclerosis — a form of MS where disability starts accumulating right from disease onset — but scrapped those plans after the Phase 3 PERSEUS trial (NCT04458051) failed to demonstrate that the therapy could lower the risk of confirmed disability progression in that patient population.
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