A new study suggests that NPI-0052 ^[1] (marizomib), a new product being developed by Nereus Pharmaceuticals, Inc., may be more active and less toxic in patients with relapsed or refractory myeloma despite treatment with Velcade ^[2] (bortezomib) and other drugs. Researchers presented the preliminary results of the Phase 1 trial on December 7 at the 51st annual meeting of the American Society of Hematology (ASH).

Found in marine bacteria, NPI-0052 acts, like Velcade, as a proteasome inhibitor. Both compounds prevent enzymes in cancer cells that regulate growth from working properly, which eventually leads to cell death. NPI-0052 is structured differently than Velcade and other proteasome inhibitors to date, which changes its effects on the body.

In the study, scientists examined both the activity and toxicity of NPI-0052 at various doses in 27 patients with relapsed or refractory myeloma. Patients received an IV injection of NPI-0052 on days 1, 8 and 15 of a 28-day cycle. Researchers gradually increased the dosage in some participants, with the final range given to patients being 0.025 mg/m² to 0.7 mg/m².

At a dose of 0.7 mg/m², NPI-0052 inhibited 73 percent of a specific type of proteasome activity on day 1 and 99 percent on day 15. In comparison, Velcade is 65 percent effective in inhibiting that proteasome activity. Two patients who had relapsed after Velcade treatment achieved significant reductions in their M-protein levels (71 and nearly 50 percent). Eight other patients who participated in the study between 6 and 15 months arrived at disease stability. Two of them had been resistant to Velcade.

Out of the eight patients treated with 0.7 mg/m², two experienced severe fatigue, loss of balance and changes in mental status which required their doses to be reduced. Other serious side effects included nausea, vomiting, dizziness, and confusion. Patients were given medications to counter those effects.

Side effects associated with Velcade and other myeloma agents such as reduced blood cell count, neuropathy (tingling in the limbs as a result of nerve dysfunction), and clotting in the veins did not occur with NPI-0052.

Another study presented at the ASH conference evaluated NPI-0052 at doses up to 0.9 mg/m² in various forms of cancer. New side effects were observed, including a distorted sense of taste or smell, hallucinations with the eyes closed, and problems with memory, concentration or behavior. Some patients also encountered a reduction in their lymphocytes, a type of white blood cell. Researchers pinpointed the maximum tolerated dosage at 0.7 mg/m².

In both studies, scientists concluded that NPI-0052 shows promise in treating relapsed and refractory multiple myeloma without causing some of the serious effects that accompany standard treatments. Clinical trials evaluating the compound’s effects in other cancers are underway.

For more information, see abstracts 431 ^[3] and 2693 ^[4] at ASH meeting Web site.