Orange Light on Generics

Last week, I blogged on the issue of generic biologics: should companies that make vaccines, monoclonal antibodies, cell therapies, etc. get 12 years of data exclusivity before competing companies begin offering generics? Or should they be held to the same standard as makers of drugs, who get five years of exclusivity?

Looks like the U.S. Senate is caving in to pressure from Pharma and the Biotech industry by opposing the Obama's "compromise" position: the Senate bill urges 12 years. But in today's New York Times, journalist Andrew Pollack suggests the exclusivity debate might not matter in the end: most biologics are protected by patents beyond 12 years after FDA approval. Meaning: short exclusivity periods advocated by various public interest groups would have no material impact on development of generic biologics, because generics would be prevented by patents. The article contains a graphic showing that patents on several leading biologics products extend well beyond 12 years.

So is this just a symbolic debate? I think not (disclaimer: I am not a health care economist!). Towards the end of the article, Pollack acknowledges that the exclusivity debate might matter where patents do not provide strong protection. That's a crucial issue for biologics. Intellectual property law around biologics is notoriously unstable and uncertain. And owing to their complex composition, generic manufacturers might plausibly argue that their products are biosimilar while not infringing patents. Advocates of the 12 year policy will argue that longer exclusivity is necessary to entice investors who might otherwise worry that lead products will not withstand patent challenges. Advocates of the shorter policy (like myself) will argue that we owe it to present day patients and their families to take that risk. (photo credit: sortofbreakit 2008).

Phased by Phase 0?

Today, Lancet ran an editorial asking whether Phase 0 trials will become a "platform for drug development." The editorial responds to the first published 'phase 0' study, this June, in Journal of Clinical Oncology (Kummar et al). These studies involve delivering very small quantities of a new drug to test its properties before giving biologically active levels to patients. They promise to improve the efficiency of drug development by screening drug candidates before they are tested in larger, riskier phase 1 trials.

The Lancet editorial notes the potential of phase 0 studies, but raises questions about their ethics: "no therapeutic benefit can be conferred by the small doses in a phase 0 study, and while taking part, patients are not allowed to enrol in a trial with therapeutic intent." As I have argued in Journal of Law, Medicine, and Ethics, however, the former issue is a red herring: normal phase 1 trials routinely, and deliberately, deliver levels of drug that are too low to cause therapeutic response. Moveover, whether phase 1 trials in themselves have "therapeutic intent" is debatable.

There are, of course, many ethical concerns surrounding phase 0 studies. Chief among them is whether patients understand their nontherapeutic nature, and whether results are publicly reported (I predict that if phase 0 methods are taken up by the private sector, many results will languish in filing cabinets). But effective engagement with ethical issues in phase 0 cancer studies requires, in my view, that we take a more careful look at whether "therapeutic intent" is really the litmus that determines whether a study pursued in patients is ethical. (photo credit: w i n t e r t w i n e d 2009)

Generic Biologics

Gene transfer, cell transplantation, monoclonal antibodies, enzyme replacements, tissue engineering all have great potential to improve health care. But will we be able to afford them? Various economists have shown that a large proportion of health care cost inflation is attributable to new technology, and the significant costs of development and production for drugs involving genes, cells, and large proteins- what regulators call "biologics"- provide grounds for concern that new biotech products will break the bank.

Questions about the affordability of biotech drugs are heating up in DC as Congress takes a look at generic biologics. Under current policy, there are no regulatory pathways for approving generic versions of biologics. This effectively means that companies that develop biologic drugs have a monopoly on them long after patents expire. Representative Henry Waxman, who previously sponsored legislation creating a pathway for generic drugs, is presently spearheading efforts to establish a way of reviewing and approving generic biologics as well.

The policy and economic issues here are profoundly complex, and much of the debate about legislation revolves around the issue of "data exclusivity." Briefly, this refers to the period after drug approval during which generic competitors are barred from using data from the innovator's clinical trials to apply for generic approval. In the U.S., for example, generic drug companies cannot file applications with FDA until five years after the new drug is approved by FDA. The aim of exclusivity is to reduce the economic impact of free rider generic companies that depend on trial data collected by the innovator.

The biotech industry, and many economists, argue that much longer periods of data exclusivity are required for biologics. They argue that without longer exclusivity periods (like 12 to 14 years), companies will have insufficient incentive to develop new biologics. Consumer advocates often argue otherwise, citing the mouth dropping costs associated with using many new biologics.

It remains to be seen who will prevail in this debate, but Waxman and the Obama administration appear inclined toward the consumer advocates, with the former urging a 5 year period, and the latter endorsing a "compromise" of 7 year exclusivity.

At stake is not simply question of markets and economics, but also one of ethics. Namely, should how should health care economies balance the need of current patients (who can ill afford expensive biologics) against those of future patients (who might benefit from greater innovation should exclusivity periods be extended)?

Sound ethical analysis must discount benefits accruing to future patients and consider the justice implications of excluding current patients from otherwise available treatment so that others in the future might benefit from new drugs. If implemented, the Obama administration's plan for generic biologics promises to reduce an important hurdle in ensuring an equitable future for cutting edge therapies. (photo credit: shazam791, a true generic brand, 2008)