Onyx Pharmaceuticals plans to file a US New Drug Application “as early as mid-2011” for potential accelerated approval of carfilzomib, the multiple myeloma drug it acquired with fellow California-based company Proteolix in October 2009.
The announcement, which helped to boost Onyx’s share price, came as the company confirmed and fleshed out the positive outcomes of a Phase IIb trial with Proteolix initially flagged up last summer.
Results of the single-agent 003-A1 study of carfilzomib, a next-generation proteasome inhibitor, in 266 heavily pretreated patients with relapsed and refractory multiple myeloma were presented at the 52nd American Society of Hematology Annual Meeting in Orlando, US.
As was previously reported, carfilzomib achieved an overall response rate (ORR, partial response or greater) of 24.1%, while the median duration of response for patients who entered the trial after receiving a median five prior lines of therapy (i.e., 13 anti-myeloma agents) was adjusted to 8.3 months from more than seven months previously.
The clinical benefit rate (CBR, minimal response or greater) in the study population was 34.2% while median overall survival (OS) was 15.5 months. Overall survival for responding patients on carfilzomib is not yet available but is expected to be more than 19 months based on current data, Onyx said.
There was also an encouraging side-effect profile. On entry to the 003-A1 trial, 77% of patients had grade 1 or 2 peripheral neuropathy (PN), which has been a problem with marketed therapies for multiple myeloma. New or worsening PN was “uncommon” in the study and grade 3 peripheral neuropathy occurred in fewer than 1% of patients, Onyx reported. There were no grade 4 PN events.
Onyx also noted that, in a subset analysis of 128 patients who were refractory to bortezomib (Velcade, Millennium Pharmaceuticals) as their last line of therapy for multiple myeloma, carfilzomib achieved an ORR of 19% and a CBR of 31%. In those who had received only one prior bortezomib regimen (122 patients), the ORR was 30% and the CBR 40%.
Bloomberg quoted analyst Howard Liang of Leerink Swann & Co as saying that expedited approval of carfilzomib may enable the drug to enter the US market in 2012, based on current studies.
If the Food and Drug Administration insists on Onyx completing a 700-patient trial currently underway with carfilzomib, that will push potential market entry back to 2014 at the earliest, Liang added.