Page 1 Page 2 Page 3 Page 4 Page 5 Page 6 Page 7 Page 8 Page 9 Page 10 Page 11 Page 12 Page 13 Page 14 Page 15 Page 16 Page 17 Page 18 Page 19 Page 20 Page 21 Page 22 Page 23 Page 24 Page 25 Page 26 Page 27 Page 28 Page 29 Page 30 Page 31 Page 32 Page 33 Page 34 Page 35 Page 36 Page 37 Page 38 Page 39 Page 40 Page 41 Page 42 Page 43 Page 44 Page 45 Page 46 Page 47 Page 48 Page 49 Page 50 Page 51 Page 52 Page 53 Page 54 Page 55 Page 56 Page 57 Page 58 Page 59 Page 60 Page 61 Page 62 Page 63 Page 6458 msfocusmagazine.org Medicine & Research Update on Cladribine By Ellen Whipple, Pharm.D. Six years ago, no oral agents had been approved by the U.S. Food and Drug Administration or the European Medicines Agency for the treatment of patients with multiple sclerosis. There appeared to be a race between several products (i.e., cladribine, fingolimod, and laquinimod) to be the first oral agent approved in either the U.S. or Europe for the treatment of patients with MS. According to Dr. BenThrower, medical director of the Multiple Sclerosis Institute at the Shepherd Center in Atlanta, many experts felt that cladribine would be the first oral agent approved by the FDA for the treatment of MS. A New Drug Application for oral cladribine as a short-course therapy for patients with MS was submitted to the Food and Drug Administration in September 2009. The NDA submission was supported by evidence from the CLARITY study, which evaluated the effects of oral cladribine in 1,326 people with RMS. Patients in the CLARITY study received either short-courses of oral cladribine or placebo. After two years, the patients who received oral cladribine had fewer MS relapses and less disability progression, than those who received a placebo. These findings were presented at the 61st annual meeting of the American Academy of Neurology in April 2009 and more recently published online in The New England Journal of Medicine in January 2010. Regulating authorities in both the U.S. and Europe were concerned about the reports of cancer in the CLARITY study. In March 2011, the FDA informed EMD Serono/Merck that it would not approve oral cladribine as a treatment for MS without more safety information. Around the same time, the European Medicines Agency also rejected cladribine’s application. Since the FDA and European Medicines Agency refusal of cladribine, three oral agents have been approved for the treatment of patients with RMS. These products include fingolimod, dimethyl fumerate, and teriflunomide. These products generally have comparable efficacyand safetydata compared to the other disease-modifying therapies currently approved by the FDA. Since the decisions by the FDA and European Medicines Agency, more data on oral cladribine as a treatment for patients withMShavebecomeavailable.Basedonthese new data, EMDSerono/Merck announced in 2016 that the European Medicines Agency has accepted for review the Marketing Authorization Application of cladribine as a therapy for patients with the RMS. According to Luciano Rossetti, Head of Global R&D for the Biopharma business, Merck, “Although there are multiple therapies available for relapsing-remitting MS, there is still a significant unmet medical need with a focus on efficacy, dosing, durability and safety. We believe that cladribine tablets, if approved, would have a first-of-its-kind dosing regimen and serve as an important therapeutic option for patients with relapsing-remitting MS.” RX Update