#ECTRIMS2016 – Investigational Leustatin Tablets Offer Clinical Benefits to Different MS Patients

Leustatin (cladribine) tablets, an investigational drug, were shown to be effective at reducing annual relapse rates, not only in MS patients, but also in patients with a first demyelinating event who later converted to a clinically defined multiple sclerosis diagnosis.

The results were shared in a presentation titled “Cladribine tablets in the ORACLE-MS study open-label maintenance period: analysis of efficacy in patients after conversion to clinically definite multiple sclerosis (CDMS),” at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Sept. 14-17 in London.

In the previous CLARITY clinical trial (NCT00213135), researchers showed that treatment with Leustatin in short-duration courses for two years significantly reduced the annual relapse rate in MS patients. The treatment sustained disability worsening in patients with active MS. The effectiveness observed in CLARITY was maintained without additional active treatment during the CLARITY extension trial (NCT00641537).

In a subsequent ORACLE-MS (NCT00725985) study, in patients with a first demyelinating event, Leustatin tablets (3.5 mg/kg and 5.25 mg/kg) significantly reduced the risk of conversion to clinically definite MS (CDMS) in comparison to placebo-treated control patients.

A counter measure in these studies included treating patients with subcutaneous (sc) interferon-beta 1a in an open-label maintenance period (OLMP) in patients who had CDMS in the double-blinded initial treatment period (ITP). Interferon-beta therapy was titrated over four weeks up to the dose of 44 mcg, and administered three times a week.

Now, researchers presented results from the ORACLE-MS OLMP study, where they determined the annual relapse rate in patients randomly assigned to receive Leustatin at 3.5 mg/kg to 5.25 mg/kg, or a placebo, in the ITP.

The team found that 109 patients with a first demyelinating event in ORACLE-MS converted to CDMS in ITP, and received at least one dose of interferon-beta 1a (median time on interferon-beta 1a was 56 weeks).

With increasing doses of Leustatin, researchers observed a decrease in estimated annualized relapse rates. Specifically, they detected a rate of 0.14 in Leustatin 3.5 mg/kg; 0.24 for Leustatin 5.25 mg/kg; and 0.42 for patients who originally received a placebo in the ITP.

“A significant treatment effect versus placebo of [Leustatin] tablets given in ITP continues to be observed in patients who convert to CDMS and switch to treatment with a different disease modifying drug (sc interferon beta-1a). Patients who had been treated with [Leustatin] tablets and who had converted to MS during ORACLE-MS ITP had lower ARR [annual relapse rate] during the OLMP, relative to those patients who had received placebo during ORACLE-MS ITP,” the team wrote in their ECTRIMS’s abstract.

Leustatin tablets are an investigational drug and are not approved for any indication in the U.S., Canada, or Europe.

This study was sponsored by EMD Serono, a sudsidiary of Merck.

“Merck is committed to advancing patient care and offering therapeutic options that help address unmet medical needs for people with MS, with a focus on efficacy, dosing, durability and safety,” Luciano Rossetti, global head of Research & Development for Merck’s biopharma business, said in a press release.