The development and approval of Xalkori crizotinib from Pfizer Inc. blazes a trail for companies with other ultra-targeted compounds to follow. But Xalkori's speed to market for NSCLC was made possible by a bit of luck in matching the right drug with patients with the right mutations; for most drugs this will take a proactive effort.
Pharmacogenetics companies and clinical researchers say sequencing has improved sufficiently to enable routine, large-scale screening for mutations that define subpopulations as narrow as that served by Xalkori, which received accelerated approval in August to treat the 3-5% of non-small cell lung cancer patients who have an ALK translocation.
The limiting factors are likely to be insufficient access to tissues for confirming a mutation's driving role in disease, and the likelihood that relatively few of the targets related to a driving mutation will be druggable.
When it works, the rewards for companies and patients will be great. Ultra-targeted therapies should show significant improvements over standard of care in subpopulations where most patients can expect to benefit.
In August, FDA granted accelerated approval for Xalkori as monotherapy to treat locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC). The oral small molecule, a dual inhibitor of c-Met receptor tyrosine kinase and anaplastic lymphoma kinase (ALK) and their oncogenic variants, targets the EML4-ALK translocation.
At the same time, FDA also approved the companion diagnostic Vysis ALK Break Apart FISH Probe test from partner Abbott Laboratories.
Pfizer was able to get