Cladribine (brand name: Mavenclad®) is manufactured by Merck Serono. It is an anti-neoplastic agent (anticancer drug) that is formulated for oral administration. In August 2017, cladribine was approved for the treatment of people with highly active relapsing forms of MS in the European Union, Norway, Liechtenstein, and Iceland. It has not been approved for use in the United States or Canada at this time. Cladribine is an antimetabolite, which works against lymphocytes (a type of white blood cell that plays a key role in the immune system's inflammatory response). Cladribine disrupts the DNA of lymphocytes, leading to depletion of T-cells and B-cells (types of lymphocyte). This depletion of T-cells and B-cells helps reduce inflammation and reduces demyelination in the CNS. In clinical research, Cladribine has been shown to reduce the frequency of MS relapses and to delay disease progression.1,2
What is the evidence for the effectiveness of cladribine in MS?
Several large-scale clinical trials have been conducted on cladribine, including Phase 3 trials CLARITY, CLARITY Extension, and ORACLE MS; Phase 2 trial ONWARD study; and long-term data from the 8-year registry called PREMIERE. In the CLARITY trial, cladribine reduced the annualized relapse rate by 67% and reduced the risk of six-month disability progression by 82%. In addition, follow-up analysis of CLARITY and CLARITY Extension found that up to 90% of those who received cladribine were free of new lesions on MRI and up to 81% remained relapse-free after 4 years. (These findings were dependent on the cumulative dose given.)1,3
How far along is cladribine in the development process?
Previously, the FDA did not approve cladribine, citing that a better understanding of the drug safety profile and overall risk-benefit profile were needed. Specifically, there were concerns about an increased risk of cancer. Now, there are more than 10,000 patient-years of data with over 2700 patients from several clinical trials, and up to 10 years of observation in some patients. The data from these combined trials shows cladribine is effective in relapsing forms of MS, and the long-term safety data has not raised concerns. Merck is expected to apply for FDA approval leveraging this combined data.1-3
What are the most common adverse effects or side effects with cladribine?
The most common side effects experienced by people taking cladribine in clinical trials were lymphopenia (a decrease in lymphocytes) and herpes zoster (shingles). Because of the risk of lymphopenia, a person's blood must be tested before receiving cladribine to ensure they have a normal amount of white blood cells. The reduction of white blood cells with cladribine is temporary. Other side effects experienced by people taking cladribine include oral herpes infections and tuberculosis (TB). Cladribine is not recommended in people with severe liver disease, kidney disease, human immunodeficiency virus (HIV), cancer, active infections, or in pregnant women, as cladribine may cause harm to an unborn fetus.3,4