In October 8, 2010, we posted on our website a multiple-choice question, asking those who perpetrated pessimistic news about Onyx (ONXX), which led to a stock selloff to explain the reason for their pessimism towards this firm. The question was:
Which one of the following four reasons made you sell ONXX?
Failure of the firm’s multiple myeloma drug carfilzomib?
FDA rejection of Carfilozmib NDA?
Recall of Nexavar from the market?
None of the above?
The correct answer, we wrote, is: None of the above.
A couple of months after the irrational sell-off of the good stock, Onyx announced the complete results from the Phase 2b 003-A1 study of carfilzomib for multiple myeloma at the American Society of Hematology Annual Meeting and Exposition, The drug, a novel proteasome inhibitor, was stunningly effective as a single-agent on patients with relapsed and refractory multiple myeloma who had received a median of five prior lines of therapy (corresponding to a median of 13 anti-myeloma agents). Carfilzomib achieved an overall response rate (ORR) (partial response or greater) of 24.1 percent and a median duration of response (DOR) of 8.3 months. The clinical benefit rate (CBR) in the study population was 34.2 percent. The median overall survival (OS) was 15.5 months. Overall survival for responding patients (? minimal response) had not yet been reached. These results are exciting.
(For complete press release copy and paste the following link: http://www.onyxpharm.com/view.cfm/711/Onyx-Pharmaceuticals-Announces-Positive-Complete-Results-from-Carfilzomib-Phase-2b-Study
Investors’ reaction to the news was huge, which was confirmed by a stock rally. What many investors missed, though, is another presentation that had taken place a day before at the same meeting. The subject of the presentation was about results from another trial with Carfilzomib in combination regimen for first line treatment for multiple myeloma. In this study led by the University of Michigan Comprehensive Cancer Center, Carfilzomib in combination with lenalidomide and low-dose dexamethasone demonstrated that all the 31 patients enrolled in the study responded to the drug combination with at least 50 percent reduction of the disease and the cancer was completely or nearly eliminated in a significant number of patients. The response was quick and continued to improve with additional treatment. More than two-thirds of the patients who completed eight cycles of therapy achieved a complete response, meaning that they showed little or no signs of cancer. The response rate is described as higher than those achieved by the best current regimens in newly diagnosed multiple myeloma. After a median follow-up of six months, all patients were alive with no progression of their cancer. These results are described as impressive.
Commenting on these results, Andrzej Jakubowiak, M.D., Ph.D., director of the multiple myeloma program at the University of Michigan Comprehensive Cancer Center and the author of the study said, “This combination treatment appears to deliver everything we expected and more. We have seen no neurotoxicity and fantastic efficacy, the best reported to date”.
The combination was well tolerated with few side effects. Peripheral neuropathy, which limits extended use of currently available multiple myeloma treatments and is the major reason patients do not continue their treatments, was mild in infrequent on the Carfilzomib combination.
The study has also included patients who were eligible for a stem cell transplant. It was interesting to learn that these patients were able to remain on the Carflizomib combination and have achieved responses similar to, or better even than those observed after stem cell transplant. This outcome delayed the need for a stem cell transplant in these patients.
Newly diagnosed myeloma is most sensitive to treatment. The degree of the initial response to first-line treatment is what leads to either progressive remission, or progressive disease, i.e., survival, or death. Patients have a better chance of living longer if their response to initial treatment is better. Carfilzomib combination for multiple myeloma had a response that points to survivability. Currently, a Phase III trial is ongoing to compare efficacy of carflizomib against the individual drugs used in the combination, i.e., lenalidomide and low dose dexamethasone on patients with relapsed multiple myeloma.
According to the American cancer association, 10,650 multiple myeloma patients still die every year out of 20,180 Americans diagnosed with the disease. The results announced to date about Carflizomib trials alone and in combination with lenalidomide and low-dose dexamethasone, or in other intended combinations would save many of the 10, 650 multiple myeloma victims.
Disclosure: We long this company.