Today’s long awaited FDA Advisory Committee meeting focused on carfilzomib’s role as a salvage therapy for patients who have become refractory to Revlimid and/or Velcade.
Dr. Anderson from Dana-Farber and Harvard Medical School, spoke in support of the drug. He reviewed the study results that were used to qualify carfilzomib for FDA fast track approval last year.
Dr. Anderson reminded the committee that all of the patients in the study he reviewed had been heavily pre-treated and entered the study with a number of co-morbidities.
And he reminded the committee that there is an unmet medical need for a drug like carfilzomib. Dr. Anderson stated that the overall survival (OS) time for patients that have become refractory to both Revlimid and Velcade is between 6 and 10 months—and he specifically referred to a salvage therapy study where OS was a short nine months.
These numbers support those I quoted from M.D. Anderson’s myeloma expert, Dr. Robert Orlowski in Houston last December. At that time, Dr. Orlowski stated that the median life expectancy for a patient refractory to both Revlimid and Velcade is a short 8 months.
Dr. Anderson emphatically reminded the committee that the need for a drug like carfilzomib (proposed trade name Kyprolis) is urgent and real.
Dr. Natalie Sacks reviewed adverse event data from Phase 1 and 2 studies thus far on behalf of Onyx.
Fatigue was the most common side-effect. She went out of her way to note that only 12% of patients from all of the studies had measurable peripheral neuropathy (PN), which was lower than averages for multiple myeloma patients in general.
Serious adverse events included pneumonia, renal failure and congestive heart failure.
It was pointed out that advancing age and risk factors for all patients with advance myeloma contributes to a seemingly high mortality rate.
Apparently, 8-9% of advance myeloma patients die of heart failure with no specific treatment.
Among 37 deaths which occurred in carfilzomib related studies, as many as 10 deaths had a cardiac component. 70% of patients in these studies already had a cardiac risk factor.
Overall mortality rate was 7% in these studies—lower than the overall averages of 8-9% of myeloma patients I referred to above.
Thus, although it is difficult to quantify, Dr. Sacks, stated that patients using carfilzomib did not experience any more severe adverse events—or death—than others in the literature. In her opinion, carfilzomib does not contribute to heart-related deaths.
She concluded by stating that Onyx Pharmaceuticals has a high degree of confidence that heavily pretreated patients with preexisting health conditions can be safely treated with carfilzomib.
Three or four different physicians that worked for Onyx on these studies spoke to the committee. I found this review process to be fascinating. Onyx was given an hour to make their case. And I thought they did that convincingly.
They concluded their presentation by reminding the committee that 20-30% of heavily pretreated patients responded to carfilzomib. The average patient in carfilzomib studies had lived with multiple myeloma for 5.2 years and had previously received 5 or more treatments. And they closed by making this point: If the FDA waits 2-3 years for Phase 3 trials to conclude, up to 30,000 patients in the United States may not have access to the drug.
The FDA’s review was actually quite positive, pointing out that overall response rate held steady across a number of different studies.
They were concerned about the number of high adverse events. They reviewed the numbers and causes of deaths. Cardiac and pulmonary adverse events were reviewed. Of the 10 patients that died, 9 had preexisting heart conditions. And close to 60 patients left the study due to serious cardiac and/or pulmonary events.
FDA officials noted that single arm trial designs make it difficult to isolate the causes of these events.
They then confirmed that overall response rates among the studies was 22%. Median response lasted 7.8 months.
The FDA would like to see data from two large, Phase 3 studies, one comparing Kyprolis with Velcade and the other with Revlimid. But no official comment recommending a delay was made.
The FDA only took 15 minutes to summarize their position.
Next, a Q/A session took place, allowing members of the committee to ask specific questions of Dr. Anderson and the physicians representing Onyx.
Questions were reasonable and specific. For example, one panel member wanted to know how well carfilzomib did in patients specifically refractory to Velcade. The answer: 18.3%
One committee member even referred to the numbers as “robust.” Another commended the high quality of the pretreated patient population in the study.
Media hysteria from the last few days aside, if I was to guess I would think that the committee would recommend accelerated approval.
Ironically, I was forced to leave for my sub-q Velcade infusion before the Q/A period ended. Tough to find good help these days! But I’m back, and I can share with you that my instincts were correct. The committee voted for FDA fast-track approval!
And I was able to interview an Onyx official after I returned. I will share that interview—and any news and updates from later this afternoon—with you on Thursday. It now seems likely that the FDA will approve carfilzomib for use in refractory multiple myeloma patients sometime in July.
Feel good and keep smiling! Pat