The European Commission has approved Merck KGaA’s Mavenclad (cladribine tablets) to treat highly active relapsing forms of multiple sclerosis (MS). The Aug. 25 decision in Brussels marks the first approval of a highly efficient oral short course therapy for MS in Europe.
Mavenclad has been shown to harness disease activity for four years after a maximum of 20 treatment days over two years.
“Multiple sclerosis is one of the world’s most common neurological disorders,” Belén Garijo, CEO of Merck Healthcare and member of the company’s executive board, said in a press release. “With the approval of Mavenclad in the European Union, we are pleased to offer patients and clinicians an innovative agent with a simplified dosing schedule as a new approach to managing active relapsing MS.”
The approval, which allows Merck to market Mavenclad in the European Union’s 28 member countries plus Iceland, Liechtenstein and Norway, builds on data from more than 2,700 patients who participated in clinical trials. Some patients have been followed for up to 10 years.
Regulators got access to data from the Phase 3 clinical trials CLARITY (NCT00213135), CLARITY EXTENSION (NCT00641537), and ORACLE-MS (NCT00725985), as well as the Phase 2 ONWARD trial (NCT00436826), and the ongoing long-term study PREMIERE (NCT01013350).
In June, the European Medicines Agency’s Committee for Medicinal Products for Human Use urged the EC to approve Mavenclad, which had earlier been rejected by both European and U.S. health authorities because of concerns about an increased cancer risk.
These concerns have, however, have receded, and Merck has produced plenty of additional data supporting Mavenclad’s effectiveness in relapsing forms of MS. Independent researchers also found the treatment to improve patients’ quality of life.
“This is an exciting moment, and one that will change the way we treat MS,” said neurology professor Gavin Giovannoni of Barts and The London School of Medicine and Dentistry, Queen Mary University of London.
Mavenclad should become available next month in Great Britain and Germany, expanding to other EU member states later one. Merck also plans to file marketing applications in the United States and elsewhere.
“Multiple sclerosis affects more than 700,000 people across Europe and has no cure to date,” said Anne Winslow, president of the European Multiple Sclerosis Platform. “New treatment options will significantly help improve the quality of life of people living with active relapsing MS.”
Her statement is supported by the results of clinical trials. In the CLARITY trial, Mavenclad reduced annualized relapse rate by 67 percent while cutting the risk of six-month disability progression, as measured by the Expanded Disability Status Scale, by 82 percent.
Mavenclad achieved this with only two short courses of treatment — with a maximum of 20 treatment days — in the first two years. The CLARITY EXTENSION trial showed that the benefits continued throughout the third and fourth year.
But as with any treatment, Mavenclad can trigger side effects, including a reduction in white blood cells and an increased risk of shingles. Because of its effects on white blood cells, treated patients must be monitored to make sure blood cell counts do not drop too low.
This also makes Mavenclad an unsuitable treatment for immunocompromised patients, including those with HIV, active chronic infections such as tuberculosis or hepatitis, or cancer.
Patients with kidney disease, as well as pregnant and breastfeeding women, will also be ineligible for treatment.
The depletion of white blood cells is, however, also part of the drug’s mechanism of action in MS. Studies show that Mavenclad depletes both B-cells, and to a lesser extent, T-cells. But the depletion is transient, and new immune cells reappear. This makes researchers believe that Mavenclad works by resetting the immune system.
“Mavenclad is a selective immune reconstitution therapy which simplifies treatment administration, by giving patients just two short annual courses of tablets in four years,” said Giovannoni. “Patients can benefit from the treatment over a longer period of time without having to continually take medication and without the need for frequent monitoring.”
Added Garijo: “This is a pivotal change in the treatment of MS which further demonstrates our unwavering commitment to advancing patient care.”