The potential role for cladribine in the treatment of multiple sclerosis: clinical experience and development of an oral tablet formulation.

BACKGROUND

Disease-modifying drugs available for multiple sclerosis (MS) require chronic, regular, parenteral administration. Effective oral MS therapies may improve long-term adherence. A number of oral therapies are in development, including cladribine--a preferential lymphocyte-depleting therapy with a well-established safety profile across other indications.

OBJECTIVE

To review information available on the safety and efficacy of cladribine in the treatment of MS, in the context of the ongoing development of an oral tablet formulation.

METHODS

An electronic search was performed to identify publications in which 'cladribine' was listed as a major index term. Results of the literature search were supplemented by other relevant secondary references and publications.

FINDINGS

The majority of published data on cladribine describe its use in diseases other than MS. However, three major, industry-sponsored, double-blind, placebo-controlled trials of parenteral cladribine were identified, involving 262 patients with relapsing or progressive forms of MS. Patients received cumulative doses of 0.7-2.8 mg/kg of cladribine over 4-6 months and were followed-up for at least 6-12 months thereafter. Individual results of these studies of parenteral cladribine indicate that it can reduce: (i) the number and volume of T1 gadolinium-enhancing lesions; (ii) the accumulation of T2 lesion volume; (iii) relapse rate; and (iv) disability progression. A dose-dependent increase in adverse events was observed, leading to selection of low doses for use in an ongoing clinical development program of an oral tablet formulation. Efficacy and safety data from four independent studies/case reports have also supported the potential benefits of cladribine in MS. While parenteral cladribine (at doses of 0.7-2.1 mg/kg) is associated with a good short-term safety and tolerability profile, additional long-term data are required--and the safety profile of the oral tablet formulation is yet to be established. To this end, the efficacy and safety of oral cladribine tablets are now being assessed as monotherapy and add-on therapy to interferon-beta-1a in two, 96-week, double-blind clinical trials of relapsing forms of MS. These ongoing studies will utilize newer diagnostic criteria and more sensitive evaluation techniques than were available at the time of the parenteral studies of cladribine.

CONCLUSION

Preliminary data indicate that cladribine is effective for the treatment of MS and has a promising safety and tolerability profile. The sustained immunologic effects of cladribine make it suitable for intermittent oral dosing, which is expected to offer benefits for patient satisfaction and therapeutic adherence.