Cladribine Tablets Safety Profile Reaffirmed With Long-Term Data

October 11, 2018

An updated safety analysis of the therapy in patients with relapsing MS, up to 10 years, has shown no new safety signals.

Gavin Giovannoni, MBBCh, PhD

New real-world and follow-up data out of the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Berlin, Germany, has reasserted the known safety and efficacy profile of cladribine tablets for the treatment of patients with relapsing multiple sclerosis (MS).

An integrated analysis from the CLARITY and ORACLE-MS trials, as well as CLARITY’s extension study and 2 additional years of data from the PREMIERE Registry, has shown no new safety signals for the therapy. The analysis totals up to 10 years of follow-up with more than 1000 patients administered either 3.5 mg/kg cladribine tablets (n = 923) or placebo (n = 641).

The treatment is taken for a maximum of 20 days over a period of 2 years. Gavin Giovannoni, MBBCh, PhD, a lead investigator in the CLARITY studies and the Chair of Neurology at Barts and The London School of Medicine and Dentistry, said in a statement that in his opinion, “we are entering an era of immune reconstitution therapy in MS, where therapy is intermittently administered but which has an effect on the disease that lasts much longer than the period of dosing.”

“The new data presented suggest cladribine tablets delivers sustained efficacy well beyond the dosing regimen with no new safety signals found in the long-term,” he added.

As previously reported, the rate of adjusted adverse event (AE) incidences per 100 patient-years for those experiencing ≥1 serious treatment-emergent AE was 3.88 for those taking cladribine tablets, compared to 3.57 for those administered placebo. Additionally, the adjusted AE incidences per 100 patient-years were also analyzed for a number of events, including serious lymphopenia, serious infection and infestations, serious herpes zoster, serious neoplasm, benign, malignant, and unspecified, though no new AEs were identified since cladribine tablets were approved in the European Union in 2017. In total, 47 adverse reactions to the therapy have been reported since that approval, with no new signals.

In a post-hoc analysis of the CLARITY EXT trial, no evidence of disease activity (NEDA-3) status in years 1 and 2 was observed to be sustained in by the end of year 4 following the 20 days of treatment with cladribine tablets. Additionally, further post-hoc analysis of the data from the CLARITY trial program indicated similar findings from previous analyses with regard to the efficacy of the treatment on MRI measures and relapses—revealing no apparent impact on the efficacy due to patient age.

Patients who were part of CLARITY showed reduced qualifying relapse rates in those aged 45 years and older, as well as younger. The number of cumulative new T1-gadolinium enhancing (T1-Gd+) lesions and active T2 lesions at week 96 of the trial were greater reduced for those taking cladribine tablets compared to placebo in both age groups.

“The data presented at ECTRIMS 2018 highlight our commitment to continuing to understand the extended benefit-risk profile of cladribine tablets,” Luciano Rossetti, MD, the head of Global R&D for the biopharma business of Merck KGaA, said in a statement. “With more and more patients able to access cladribine tablets globally, it becomes increasingly important for us to invest in scientific research that helps to clarify how patients may benefit from our therapies.”

REFERENCES

1. Up to 10-Years of Follow-up Data Reaffirm Safety Profile of Investigational Cladribine Tablets [press release]. Darmstadt, Germany: Merck KGaA; Published October 10, 2018. emdgroup.com/en/news/cladribine-release-10-10-2018.html. Accessed October 11, 2018.

2. Cook S, Giovannoni G, Leist T, Syed S, Nolting A, Schick R. Updated safety analysis of Cladribine Tablets in the treatment of patients with multiple sclerosis. Presented at ECTRIMS 2018; October 10, 2018; Berlin, Germany. Abstract #P875.