Dr. Berenson Discusses Early Phase Proteasome Inhibitors

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Dr. James Berenson, from the Institute for Myeloma and Bone Cancer Research, Discusses Early Phase Proteasome Inhibitors

James R. Berenson, MD, Medical and Scientific Director, Institute for Myeloma & Bone Cancer Research, Chief Executive Officer, Oncotherapeutics, discusses 4 proteasome inhibitors that are in early development, some of which are similar to currently approved agents, such as bortezomib (Velcade), while others are completely unique.

Millennium Pharmaceuticals is developing a follow-up compound known as MLN9708, which is given both orally and intravenously (IV). Phase I, open-label, dose-escalation studies are examining the maximum tolerated dose for both the IV and oral version of this agent. Early studies have suggested activity in multiple tumor types.

Nereus Pharmaceuticals is examining a small molecule proteasome inhibitor, NPI-0052, that targets the beta-lactone ring, a method that is different than previous compounds. The trials for this agent are currently in phase I, and have demonstrated interesting pre-clinical results.

CEP-18770, a compound in development by Cephalon, is designed to overcome resistance to bortezomib. Trials have given the agent in combination with bortezomib, which induced complete regression of bortezomib sensitivity and significantly delayed the progression of resistance.

Onyx Pharmaceuticals is developing another proteasome inhibitor, ONX 0912, in addition to carfilzomib, an agent that is currently seeking approval from the FDA for use in multiple myeloma. The 0912 agent, which inhibits the 20S proteasome, is still in early development.

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