Pfizer granted accelerated OK for Xalkori in NSCLC ahead of schedule
This article was originally published in Scrip
With the speed in which the US FDA has been approving new cancer drugs and the fact that the agency has OK'd three new therapies targeted at the disease this month well ahead of schedule leaves one to wonder if the head of the oncology drugs office had promised his staff the remainder of the summer off if they put the pedal to the metal.
In approving Pfizer's anaplastic lymphoma kinase (ALK) inhibitor Xalkori (crizotinib) on 26 August, the FDA also has for the second time this month cleared for marketing a cancer therapy along with a companion diagnostic aimed at ensuring a targeted drug has the best chance of working in the intended population.
Indeed, the agency on 17 August granted its OK to Genentech's and Plexxikon's BRAF inhibitor Zelboraf (vemurafenib) to treat metastatic melanoma and a first-of-a-kind companion diagnostic intended to determine if a patient's melanoma cells have the BRAF V600E mutation (scripingelligence, 18 August 2011).
Pfizer's drug received accelerated approval to treat patients with is ALK-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC) based on Abbott Molecular's Vysis ALK Break Apart FISH Probe Kit, which identifies the presence of the ALK fusion gene.
As was the case with Zelboraf and its companion diagnostic, the FDA approved Xalkori and the Vysis companion test well ahead of the expected target dates – with the latest coming about a month early.
The FDA this month also approved Seattle Genetics' Adcetris (brentuximab vedotin) for Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma – with that approval coming 11 days early on 19 August (scripintelligence, 22 August 2011, 23 August 2011).
Dr Richard Pazdur, director of the FDA's Office of Oncology Drug Products, said the approval of Xalkori with a specific test not only allows the selection of patients who are more likely to respond to the drug, but also may ultimately result in fewer adverse effects.
Pfizer said it worked closely with the FDA and Abbott to ensure the simultaneous review and approval of Xalkori and the diagnostic test – marking the first time a lung cancer medication was developed and approved in parallel with a companion diagnostic.
Xalkori, said Dr Paul Bunn, professor of medicine and the James Dudley chair in cancer research at the University of Colorado, Denver, "represents a paradigm shift in NSCLC treatment, where we're moving away from a one-size-fits-all approach to biomarker-based treatment decisions".
"By truly understanding the underlying genetic drivers of NSCLC, such as ALK, we can select patients who are more likely to respond to treatment,” Dr Bunn added.
Pfizer said Xalkori will be made available immediately through a number of specialty pharmacies.
The New York-based pharma giant noted that Xalkori is the first new drug approved in the US in more than six years for lung cancer, a disease that is responsible for more deaths each year worldwide than any other type of cancer.
Xalkori’s safety and effectiveness were established in two multicentre, single-arm studies enrolling a total of 255 patients with late-stage ALK-positive NSCLC.
For the studies, a sample of patients' lung cancer tissues were collected and tested for the ALK gene abnormality prior to study enrollment.
The trials were designed to measure objective response rate (ORR), the percentage of patients who experienced complete or partial cancer shrinkage. Most patients in the studies had received prior chemotherapy.
Results of the trials demonstrated ORRs of 50% and 61% in patients with advanced ALK-positive NSCLC.
Xalkori's approval is an important win for Pfizer, given that the drug maker is facing the beginning of its patent expirations in November for its top-selling cholesterol lowering agent Lipitor (atorvastatin).
Pfizer has applications for crizotinib filed in Japan, Korea and Europe (scripintelligence, 18 May 2011, 18 August 2011).