Molecular-Based Therapies No Panacea for Ailing Pharma

Last week the FDA approved Xalkori (crizotinib), a new product from Pfizer, to treat a rare type of late-stage lung cancer among people who show an unusually high activity of a certain gene. Some of the equity analysts that cover pharma, always eager for news that will encourage trading, expressed uncommon glee at the news. Sanford Bernstein & Co., for example, wrote that "critozinib's approval helps affirm the notion that PFE is likely to have one of the most productive pipelines in our coverage universe" and justifies their recent upgrade of Pfizer's stock. That's a lot of cheering for a product to treat just 6,000 patients a year in the US.

While Xalkori's sales will not replace those of Lipitor or any of the other blockbusters set to lose patent protection, some analysts appear delighted by the fact that the product is a molecular-based or targeted compound that addresses a unique and focused chemical abnormality. As such it can potentially be highly effective at affecting just the disease-causing problem, albeit for a highly limited population, while leaving other processes and tissues undisturbed. At least that is the theory behind molecular-based therapies as an approach to personalized medicine. The realities, however, are more complicated.

The first difficulty arises from the fact that the molecular changes targeted by such therapies don't always account for the disease or condition requiring treatment. So for example, one can turn off a gene that is abnormally "expressed" in a fair number of patients with the disease and still fail to cure it or bring substantial relief.

Secondly, in a situation that often appears with molecular-based therapies, the disease develops resistance to the medication, frequently after just a period of months. That appears to be the case with Zelboraf, a product from Roche that the FDA also approved last month for treating metastatic melanoma. Effective treatment then requires the use of several different drugs, an approach known as "cocktailing." One company's molecular-based product, for that reason, can also stimulate sales of a competitor's drug that's also needed in the cocktail. Some observers even speculate that this might cause companies to slow development of their compound in order to command an even higher price as the drug that "gets a cocktail up on its feet." The prospect of two companies in such a situation playing Alphonse and Gaston from the famous comic strip would be bitterly ironic.

Then in terms of any pharma company's economic model, the question arises about how many such "niche busters" are required to equal one, conventional blockbuster. As discussed last week, Pfizer's repurposing of a moribund, nine-year old product as a niche therapy emerged as feasibility after CEO Ian Read discussed reducing the company's equity by jettisoning 40% of its operations. It remains to be seen how many CEOs will make their companies smaller so they can develop niche products that are as risky as potential blockbusters. CEOs generally don't receive higher compensation for running smaller companies.

Pfizer stated that it plans to charge $115,200 per patient for each year of Xalkori treatment. That raises another sticky question for molecular therapies. Their narrow targeting of patient populations assumes annual pricing levels that range between $50,000 and $200,000 per patient per year. Insurers appear willing to absorb those costs for 6,000 patients a year and then pass along any higher, total costs by raising premiums. Pfizer, Roche and other pharmas claim that half or more of their pipeline drugs are molecular targeted. With premium costs already doubling every decade, it remains a question of how the health care system will absorb the increased costs when a majority of drugs are priced in six figures.

Finally, molecular targeting usually requires the simultaneous development of a companion diagnostic to discern which candidates may benefit from the drug. Roche made this the cornerstone of its R&D approach 13 years ago when it acquired Boehringer-Mannheim and stated that the development of diagnostic biomarkers would precede therapeutic development. The idea is clever but only a very few products (e.g., Herceptin) have been developed in the intervening years under that approach.

Targeted molecular therapies will doubtlessly make their contribution, but right now they have miles to go before becoming a golden path.

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