Merck Eprova Seals Agreement With Isofol Medical For Modufolin

Merck Eprova has signed an exclusive license agreement with Isofol Medical of Sweden to utilise Merck Eprova’s proprietary folate compound Modufolin in oncology. The use of Modufolin is expected to enhance effectiveness in cancer treatment. Merck Eprova will be providing Modufolin, the active metabolite of LV (Leucovorin), for use in clinical trials and commercial drug products.

After years of intensive research, Merck Eprova has succeeded in developing a stable form of the reduced folate Modufolin ([6R]-5,10-methylenetetrahydrofolate).

Modufolin is a biomodulator originally designed to replace LV as the preferred folate to enhance the activity and reduce associated toxicity of 5-FU (5-fluorouracil). The active form of 5-FU is an inhibitor of the key enzyme TS (thymidylate synthase). Blocking the synthesis of the nucleotide thymidine leads to inhibition of DNA replication and cell death. The effectiveness of 5-FU/LV in combination therapy may be limited due to several metabolic conversions of LV required to generate the pharmacologically active folate compound Modufolin. In contrast Modufolin does not need any further metabolic activation. In the tumour tissue this specific form of folate is directly usable by the target enzyme TS, potentially allowing 5-FU to work more effectively.

Isofol Medical will conduct phase I and II studies using a combination of Modufolin and antifolates starting in autumn 2009 and expected to be finished by the end of 2010.