Pharma’s Cutting Edge

I’m happy to report that science has prevailed in the debate over study designs that took place as part of Wednesday’s CRDAC meeting to discuss FDA’s draft guidance on studies and labeling for anti-hypertension drugs. In a nutshell, the advisors voted overwhwelmingly in favor of maintaining placebo-controls in a variety of hypertension superiority studies. They did so with the proviso that appropriate subject protections always be in place (i.e. “rescue” criteria). It’s gratifying to see that opinion leaders maintain a healthy respect for science in the face of growing pressures from alarmist industry-bashers to abandon it (in favor of restricting access to new drugs). Placebo controls (that is, direct comparisons with a placebo) remain the best way to control clinical tests of efficacy and safety of new drugs, in terms of accuracy and efficiency. Until or unless a better way is found, industry should maintain a voice in the debate on the side of science.

Interesting to read of Mr. Taurel’s lament of the tough environment faced by Lilly (and others) for the benefit of its shareholders. I’m not sure I see the value to the company in this type of honesty, but there’s no doubt that Mr. Taurel’s is a relatively loud voice in a chorus of large pharma CEOs singing the same song. But if the chorus is now in the mood to sing sorrowfully to its shareholders, why not lay it all on the line? Things are bad now for innovator drug companies, but they’re no where near as bad as they’re going to be in the not-too-distant future.

Consider just a few of the portents:

• Widespread government-funded drug programs covering large proportions of those who use medicines, each with upwardly mobile costs due to developed-economy expansions in elderly populations and rising costs of drugs that outpace price inflation;
• Governments almost universally under pressure to reign in healthcare spending, because it consumes a large and growing portion of government spending;
• Very large and increasing numbers of people in the U.S., the largest drug purchaser, without any type of health insurance or drug coverage;
• Successful efforts by powerful groups (elderly, third-party payors, healthcare providers, etc) and populist opinion-makers in the developed world to destroy the once-favorable (or at least tolerable) public image of the pharmaceutical industry, hampering the industry’s ability to influence public policy and healthcare practice, to collaborate with non-industry scientists and clinicians and to recruit and retain top talent;
• The rise of a “biogenerics” industry, first in Europe and coming soon to the U.S.

So, things are tough and they’re going to get tougher. Why then do I believe that there are good answers to these problems for the industry as a whole? Why do I believe that the industry’s best days lie in front of it? I believe it because I am convinced that sick people really don’t like being sick, that healthy people want to stay healthy (if it’s not too much trouble), and that it is sound policy for governments to promote health for all their citizens through the appropriate use of medications. A most important premise is that I also believe the pharmaceutical industry to be in the best position to deliver on these fundamental desires. The answers to the industry’s woes, then, are not likely to come from focusing on a bleak future but instead by looking backwards, to the reasons underlying the growth of the industry. Because oftentimes the best path forward first requires a step back and a broad view of the landscape.

The FTC report outlines the calendar year 2005 experience as reported to FTC of US “Brand”-Generic and Generic-Generic settlements, the former referring to patent disputes involving the innovator’s brand drug. As you might know, FTC has lost a number of its challenges to innovator-generic settlements recently, which appears to have emboldened some dealmakers to craft agreements that haven’t been seen since 1999–those that both restrict generic entry and provide direct or indirect compensation to the generic company (see the left side of figure 3 and text for a description). Unfortunately, for firms that are cutting deals, no deal term details are provided by FTC for benchmarking purposes. Based on personal experience and the experiences of my colleagues, I can tell you that these deals are all over the map. FTC promises to take a close look at these deals, but if recent history is predictive of trial outcome, FTC is likely to challenge only the most egregious examples of apparent anti-competitive behavior in court. Clearly, FTC’s hope is that Congress will use these data to guide policy when they re-visit Hatch-Waxman (when exactly that will occur remains unclear).

On an unrelated topic, I’ll be tackling NICE and its recent evaluation of Exubera in May’s Pharma’s Cutting Edge story. The focus will be on the reasons provided by NICE for their conclusion that Exubera is unlikely to be cost-effective. I will not try to play Monday morning quarterback. Rather, I’m interested in exploring the weight of evidence required for cost-effectiveness demonstrations with a chronic-use, incrementally innovative, NME like Exubera and whether it is feasible for pharma R&D programs to demonstrate cost-effectiveness for such products prior to first launch. Look for it or sign up to receive the PCE RSS feed on the main page.

Remember, FDA’s Approvables and Related NDA/BLA Actions is now available from Pharma Growth Strategies. It is required reading for any manager responsible for planning or reacting to FDA approval for an NME or novel protein therapeutic. Discounts are available for multi-user orders.

The headline article gives the impression that major drug companies missed the metabolomics boat when it sailed a few years ago. They didn’t. They’ve been exploring the technology since its use in clinical studies first became practical. Note that metabolomics can theoretically be used in tandem with proteomics and genomics (and even glycomics) to predict disease/drug response. More than one company is pursuing this tandem approach. See, for examples, BG Medicine, Health Discovery and Target Discovery. Leading metabolomics biomarker applications firms include Metabolon , ESA Biosciences, Phenomenome and Icoria.

Just wanted to let my readers know that the PGS report describing recent FDA experience with approvable actions is now available for purchase at http://www.pharmagrowth.com/approvables.html. It’s the first report we’ve made available to the general public. The report covers in detail the approvables process and describes the impact an approvable decision has on eventual NDA/BLA approval. Importantly, the report also finds that certain FDA divisions are more (and less) likely than others to issue approvable actions and documents the issues most likely to result in approvability, and their impact on approval time. These data are essential to anyone responsible for contributing to US new drug approval or who depend on knowing the likely timing of US new drug approval. If you think about it, that just about all managers involved with new drug development and marketing. It’s important stuff, and it’s not available anywhere else.