The reception for Pfizer’s crizotinib at this year's Asco conference could probably not have been more positive, despite only phase I data being presented. The results were considered spectacular and the trial got top billing, one reviewer even suggested that a large ongoing phase III study was probably not needed.
Although crizotinib is only being tested in a small sub population of lung cancers – those whose tumour expresses the EML4-ALK gene and who tend to be non smokers – this is thought to represent 40,000 patients worldwide, a subset that represents a major entity itself. Considering how specifically targeted agents can justify significant price premiums, crizotinib is now likely to become one of the most closely watched candidates in Pfizer’s oncology pipeline.
The gene EML4-ALK, which leads to the creation of an activated tumour-specific protein called ALK, was identified as a driver of non-small cell lung cancer (NSCLC) a couple of years ago. Around 3-5% of NSCLCs are thought to have this gene, and patients tend to be young, male, never or hardly ever smoke and unfortunately rarely respond to standard chemotherapy.
Pfizer discovered that crizotinib, also called PF-02341066, inhibits ALK, which is implicated in growth and survival pathways in tumour cells.
The phase I study presented at Asco revealed some staggering results, considering how poorly these patients tend to respond to currently available therapies.
Data was presented on 50 of the 76 ALK positive patients treated, who had received on average three prior therapies to treat their cancer. Objective response rate was 64% with durable responses of up to 15 months detected. The researchers calculated that there was a 72% probability of patients being progression free at six months, with over 90% of patients showing tumour shrinkage; final progression free survival data is not yet available.
The toxicity profile was largely manageable, with nausea and vomiting the most frequent.
Pfizer has already started a phase III trial in this population, seeking to recruit 318 patients and pitting the drug against pemetrexed or docetaxel in patients who have already failed on one platinum-based chemotherapy. Results are expected mid-2012.
Hard to imagine
This level of activity prompted a huge amount of excitement, even from a reviewer at the conference’s plenary session, an event that normally serves to temper the sometimes frothy interpretations from the companies presenting the data.
Dr Martin Edelman of the University of Maryland even questioned the need for the pivotal trial, given the “striking activity” seen.
“I’m reluctant to ever recommend against a randomised clinical trial, but this time it may be different,” he said.
“Though I expect a broader experience may temper these results it is hard to imagine they will change significantly. While only representing 3 to 5% of NSCLC, these results represent an advance for the six to ten thousand patients in the United States and the tens of thousands in the rest of the world with this disease,” he said.
Currently analysts are only forecasting sales of $79m by 2016 for crizotinib, a figure that is likely to rise on the back of these results. It certainly represents a niche market, but as Dr Edelman pointed out, the estimated 20,000 cases in the US each year equals the incidence of ovarian cancer.
It also represents a success in the quest for targeted and personalised medicines, which not only offer an almost guaranteed and predictable clinical success rate and fewer side effects, but a strong position from which to start bargaining with payers.
Whilst cost effectiveness was certainly discussed more frequently at Asco this year than in the past, it is not the primary focus of this conference. However, for the companies developing these new, expensive agents this issue is only going to become more pressing, and it will certainly be easier to justify a premium price for exquisitely targeted agents like crizotinib.