Main point is the evidence presented at ASH (American Society of Hematology) that Carfilzomib will be approved eventually by the FDA and become Onyx's (ONXX) second commercial therapy.
Repeated news about working with Ono Pharmaceutical of Japan for Carfilzomib for multiple myeloma. It is in a class of drugs known as proteasome inhibitors. It causes cell death by preventing protein degradation, essentially poisoning the cell with its own products. The hope is that it kills cancer cells with minimal harm to other cell types.
A Phase II trial of Carfilzomib (003a1) has been completed and data was presented at ASH. This was for refractory multiple myeloma, in other words for patients who have received other therapies, but then had the disease progress. Median survival expectation for such patients is currently about 9 months. Study had over 200 patients, endpoint was overall response wait, adjudicated by an independent monitoring committee. Median patient time from diagnosis was 5.4 years. Most patients had pre-existing peripheral neuropathy. Typically had had 5 prior lines of therapy (different drugs). In other words, a very sick, very previously treated group. Overall response rate was 24%, with another 10% with minimal response. Duration of response was 8.3 months, including minimal response patients. Number and type of prior therapies did not seem to influence responses. Median overall survival was 15.5 months. Adverse events were modest for this type of therapy. Conclusion is that Carfilzomib has a robust benefit for this patient population.
004 study of Carfilzomib was a non-randomized 125 patient open label trial also with refractory multiple myeloma, in two dose cohorts. Dexamethasone was administered at beginning of trial. Median age was mid-sixties, about 3.5 years of prior therapy, typically 2 prior lines of therapy, including stem cell transplants in 73 percent. Overall response rate for cohort 1 was 41% cohort 2 was 53%. Responses were relatively fast. Time to progression 8.3 for cohort 1, with cohort 2 median time to progression has not been reached. Typical modest adverse events. Showed a very impressive overall response rate with good tolerance over extended periods of time.
In the trial of therapy naive newly-diagnosed multiple myeloma patients with Carfilzomib plus two current best approved treatments (CRD), with relatively healthy (compared to the two trials above) patients in stage 2 or 3, median age was 59. Neutropenia was surprisingly low and mild, and neuropathy was minimal. 55% complete response rate, one of the best we have seen. 22% had no detectible disease. Nearly 100% had some response. Showed the regimen did not adversely affect stem cell collection. No patient has progressed, and all survived. Concludes regimen is "highly active, demonstrating rapid responses in newly diagnosed myeloma." Consensus of myeloma experts is the results compare favorably to best current therapies.
In refractory patients, many had recieved a different proteosome inhibitor therapy, notably Velcade (Bortezomib). So the response that shows differentiation from other such therapies. In patients who are refractory, the medical community considers minimal response to be significant, but it would not be significant in first-time myeloma patients.
Analysts questioned the characterization of the sickness of patients compared to Velcade trials; the doctors explained why, if anything, the patients were sicker. Patients were able to stay on therapy longer because of the tolerance patients had for it. Doctors insisted "this is the best drug in the myeloma space."
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