History in multiple sclerosis
In the mid-1990s, Beutler, in collaboration with Jack Sipe, a neurologist at Scripps Institute, ran several clinical trials exploring the utility of cladribine in multiple sclerosis, based on the drugs immunosuppressive effects. Sipes insight into multiple sclerosis, and Beutlers interest in multiple sclerosis due to his sister having the disease, initiated a very productive collaboration. Ortho-Clinical, a subsidiary of Johnson & Johnson, filed a new drug application for cladribine for multiple sclerosis in 1997 but withdrew it in the late 1990s after discussion with the FDA proved that more clinical data would be needed.Ivax acquired the rights for oral administration of cladribine to treat multiple sclerosis from Scripps in 2000, and partnered with Serono in 2002. Ivax was acquired by Teva in 2006, and Merck KGaA acquired control of Seronos drug business in 2006.An oral formulation of the drug with cyclodextrin was developed: 16  by Ivax and Serono, and then Merck KGaA conducted clinical trials. Merck KGaA submitted an application to the European Medicines Agency in 2009, which was rejected in 2010, and an appeal was denied in 2011.: 4–5   Likewise Merck KGaAs new drug application with the FDA rejected in 2011.The ratio of benefit to harm was not clear to regulators, and further studies were requested to address concerns related to severe lymphopenia and cancer cases observed during pivotal trials. : 54–55  Clinical studies of multiple sclerosis were still ongoing at the time of the rejections, and Merck KGaA committed to completing them.
Due to this increased risk, it is recommended that patients are screened for varicella zoster virus and antibody-negative patients are vaccinated prior to receiving treatment. In an analysis of post-approval data, as of 2020, no new infection safety signals were observed in over 18,000 patients.Progressive multifocal leukoencephalopathy has been reported in patients with hairy cell leukemia treated with parenteral cladribine. However, in up to 10 years of follow-up of patients receiving cladribine tablets for multiple sclerosis, no cases of progressive multifocal leukoencephalopathy have been observed; baseline MRI must be performed prior to initiating treatment.In clinical trials, malignancies were observed more frequently in patients treated with cladribine tablets compared with patients who received placebo. Compared with a matched reference population from the Global Cancer Observatory  database, cladribine tablets had no increased risk of malignancy in long-term real-world evidence data. Research directions
Cladribine has been studied as part of a multidrug chemotherapy regimen for drug-resistant T-cell prolymphocytic leukaemia. References
External links
"Cladribine". Drug Information Portal. U.S. National Library of Medicine.