Some Facts About “Niche Blockbusters”

On August 30, Jonathan Rockoff wrote a great story in The Wall Street Journal on a newly FDA-approved Pfizer lung cancer drug called crizotinib (to be sold as “Xalkori”).  The article, “Pfizer’s Future: A Niche Blockbuster,” details the history behind the discovery and development of this breakthrough medicine.  Essentially, crizotinib is an ALK inhibitor that targets the genetic abnormality that causes about 5% of new lung cancers that are diagnosed each year.  The beauty of this drug lies in the fact that a patient newly diagnosed with lung cancer can undergo a genetic test to determine if his or her lung cancer is ALK dependent.  If it is, then the physician now has a drug that is almost guaranteed to work in this patient.

The crizotinib story is not unique.  Roche also has recently launched vemurafenib, a targeted drug for melanoma.  We are moving away from the days when the only drugs that an oncologist had to treat his or her patients with were general cytotoxic compounds that come with myriad toxicities.  The rapid advances being made in understanding the genetic basis of disease have led to the discovery and development of new drugs like these.  But pharmaceutical R&D has been moving into this direction for a decade.  After all, drug discovery is not an overnight process and the research programs that are yielding these breakthroughs were started a decade ago.

Thus, I am surprised by some of the reaction that has appeared following Rockoff’s article.  Twitter has lit up with comments like: “Can targeted drugs save Big Pharma?” “Perhaps the pharmaceutical industry has come kicking and screaming (to this)” “New cancer pill gives hope, new strategy” “There has been a paradigm shift.”  There still remains the view that pharmaceutical companies are only interested in Lipitor-like blockbusters (peak sales of >$13 billion) and that smaller commercial opportunities are disdained.  Of course, every company would love to have a drug with enormous sales.  But very significant commercial returns can be made with crizotinib that more than justify its clinical development.

A number of years ago, I was asked by an industry analyst if I felt that the inevitable fractionation of patient populations by genetic subtype would be a death knell for big pharma.  His rationale was that diseases like lung cancer would be treated with agents specific to a particular mutation for a subtype of lung cancer.  Designed for very few patients, this process would result in treatments  that are far less commercially viable than a lipid-lowering agent designed to treat millions.  I explained that most drugs that are broadly prescribed do not work in a significant percentage of patients.  The current paradigm is for physicians to prescribe drugs and then monitor their patients to see if the drugs are working.  Often, patients come back complaining that their drug hasn’t helped, leading the physician to try something new.  This overall process is costly, inefficient and frustrating to all concerned.  By having specific, targeted drugs, physicians will have the confidence that the new medicine will help their patients, the patients will have confidence that the pills they are taking will help them, and payers will have confidence that they are paying for a worthwhile treatment.  In such a world, while the number of patients taking the drug is relatively smaller, better pricing for the drug should be obtainable due to improved drug effectiveness.  Basically, you might not have a few 10 billion dollar selling drugs, but you’re likely to have many billion dollar products.

This scenario is being borne out by crizotinib.  In his article, Rockoff reported that market analysts are predicting peak sales of crizotinib to exceed $1 billion.  If true, this drug would be in the top third in sales for all of Pfizer’s portfolio.  Some might argue that the only reason that crizotinib will be a commercial success is that, as a cancer drug, it can command premium pricing.  Perhaps this is true.  But hopefully, genetically targeted drugs will be developed for other polygenic diseases like depression, schizophrenia, migraine, etc.  These patient populations should be large enough to support niche-like products with a reasonable price.

Targeted drugs have been envisioned and sought for over a decade.  The first wave of these are now hitting pharmacy shelves.  This is great news for patients and physicians – and not too bad for the companies developing them either.