Carfilzomib, a new drug similar to Velcade (bor­tez­o­mib), has been shown to be effective against multiple myeloma in re­lapsed and refractory patients.

Like Velcade, car­filz­o­mib (also called PR-171) is a proteasome inhibitor that blocks the activity of proteasomes, cellular complexes that break down proteins.  Without proteasome activity, it is believed that cells self-induce death (apoptosis), thereby inhibiting tumor growth.

A Phase I study shows that car­filz­o­mib ther­apy results in greater than 80% proteasome inhibition.  Two ongoing Phase II studies have dem­onstrated complete or partial positive responses in 18% to 54% of patients, depending on the level of prior treat­ment.  For more in­­for­ma­tion about the clinical trials, click here.

An advantage of car­filz­o­mib is that it reduces peripheral neu­rop­athy (pain and numbness in the hands and feet) in comparison to Velcade.  Velcade’s boronic acid warhead has been shown to produce "greater off-target activity" than the epoxyketone warhead used in car­filz­o­mib.  The improved specificity of car­filz­o­mib means less collateral damage on the cellular level, which translates to fewer or less severe side effects for the patient.

Pre-clinical studies are now in place to explore com­bi­na­tions of car­filz­o­mib and other drugs.  One such possibility, called "synergistic killing," introduces car­filz­o­mib after another chemical agent freezes cell growth.  This makes the drug more effective as a proteasome inhibitor.

Sources: Abstract 2657, 864, 865, 3670.