Data showed that the drug lowers both immune B-cells and, to a lesser degree, T-cells. But the numbers of both cell types are back to normal by year two, and clinical trials showed that patients stayed relapse-free for another two years, suggesting that the treatment somehow resets the immune system.
Researchers presented the data at the June 24-27 3rd Congress of the European Association of Neurology (EAN), in Amsterdam, the Netherlands.
“These data presented at EAN Congress 2017 bring the MS treating community closer to understanding the mechanism of action of Cladribine Tablets,” Per Soelberg Sørensen, who presented the study at EAN 2017, said in a press release. Sørensen is the Head of MS Research Unit at the Danish Multiple Sclerosis Centre,
“These data support the emerging theories around the ability of some agents to selectively ‘reset’ the immune system without the secondary autoimmunity that we sometimes see with treatments for relapsing MS. This would represent a significant advance in the field.”
Phase 3 trials of Mavenclad — the trade name Merck chose for cladribine in its application for approval in Europe — dosed the tablets in two treatment rounds in the trials’ first two years. Patients took the pills for a total maximum of 20 days, and were then followed for an additional two years without further treatment.
Analyses showed that Mavenclad rapidly lowered the number of immune cells, with the lowest levels reached after 13 weeks. After that, the cells started re-emerging. Researchers said that T-cells were not depleted to the same extent as B-cells.
By the end of year one, 89.1 percent of all patients had normal immune cell counts. At the end of year two, the number was 88.3 percent.
Data from the Phase 3 trials — CLARITY (NCT00213135), CLARITY EXTENSION (NCT00641537), and ORACLE-MS (NCT00725985) — showed that the treatment lowered relapse rates and reduced the risk of disability progression in relapsing patients, and lessened the risk of a definite MS diagnosis among people at risk of developing the disease.
The data prompted Merck to apply for approval of Mavenclad in the EU. The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) recently recommended the European Commission approve the drug. The European Commission is expected to deliver a final decision on Mavenclad’s Marketing Authorization Application later this year.
“Following last week’s positive CHMP opinion, this integrated safety data, including 8 years of follow-up in some patients, further supports the use of cladribine tablets as a treatment option for patients with MS,” said Luciano Rossetti, Global Head of Research and Development for the biopharma business of Merck.
In 2010, EMA initially rejected cladribine, followed by a rejection by the U.S. Food and Drug Administration (FDA) in 2011. The rejection was based on a concern of more cancer cases among treated patients. Since then, extension trials have proven the safety and efficacy of the drug.
Cladribine tablets are not yet approved for the treatment of any indication in the United States, Canada and Europe.