Abbott Reformulation a Bad Deal

Abbott Reformulation a Bad Deal

April 11th, 2012 // 12:36 pm @ jmpickett

Source: Pharmalot

In 1998, Abbott Laboratories launched the TriCor cholesterol pill, which the drugmaker turned into a money-making machine thanks to an aggressive patent strategy involving numerous reformulations. Basically, Abbott retired one version of TriCor and replaced it with a modified version, which prevented generic substitution. The approach succeeded, even though a large study found the pill had little effect on cardiovascular outcomes.

This tale, itself, is not new. Three years ago, federal and state authorities began investigating this Abbott strategy for protecting its TriCor franchise, which exceeded $1 billion in sales by then. But in the interim, the nation’s health care system has been paying the price. If all patients taking some version of TriCor switched to a generic, which is half the price of the branded drug, annual savings of about $700 million could be realized, a new paper argues.

The authors, whose work appears in the Archives of Internal Medicine, traced the TriCor story in order to make the point that the sort of tactics employed by Abbott – which allegedly involved destroying older TriCor inventory and detailing only a newer version to physicians – can have the unfortunate effect of perverting the system created to allow drugmakers to protect their ideas and investments.

“Many experts are questioning whether this billion dollar drug provides any benefit. What they did was legal, but I wish they had invested that much ingenuity in bringing to market new products that delivered value to patients and society. And I wish clinicians had asked whether the new formulation was any better than generics. That approach would have save a lot of money,” says Harlan Krumholz, one of the co-authors, who is a cardiologist and professor of medicine at Yale University, and also a board member of the Patient-Centered Outcomes Research Institute.

The TriCor story involved a few different pills – there was TriCor-1, which was replaced with TriCor-2, and the Abbott tactics made it possible for the newer formulation to quickly grab 97 percent of all prescriptions, according to the paper. However, TriCor-2 was approved based on bioequivalence studies, which meant there was no market exclusivity and generic rivals could jump in. So Abbott sued and worked on tweaking its pill and creating TriCor-3.

What happened? Abbott again used bioequivalence data linking its new formulation to clinical trials of Tricor-1 for its new drug application submitted to the FDA. The new version had a “small” convenience claim: TriCor-3 could be taken anytime; the earlier versions had to be taken with food. But this claim was based on meeting bioavailability criteria. Yet the authors note Abbott did not submit comparative studies demonstrating superiority over earlier formulations.

Just the same, TriCor-3 was approved and, suddenly, TriCor-2 became scarce. And thanks to patent litigation, there were still no versions of TriCor-2, anyway. At the end of 2006, TriCor-3 had quickly dominated prescriptions. What happened next? In December 2007, just before Teva Pharmaceuticals sought approval for a generic version of TriCor-3, Abbott sought approval for its fourth formulation, called Trilipix.

The drugmaker changing the dosing and switching back to a capsule formulation, changed the active ingredient by presenting bioequivalence data comparing Trilipix with Tricor-1, and performed clinical trials measuring surrogate markers. Trilipix was granted data exclusivity for three years, through December 2011, “despite similarities with earlier formulations and limited outcomes data supporting… use,” the authors write.

Why might this matter? “There is no evidence that Abbott’s successive reformulations… have improved patient outcomes. Abbott’s NDAs presented bioequivalence evidence, not comparative data, that demonstrated the benefit of its next-generation products,” they conclude. Authorities recognized the antitrust implications and Abbott settled numerous lawsuits, paying more than $300 million, but that was less than 4 percent of its TriCor franchise sales to date.

The problem, they argue, is the patent system and emphasis on shareholder returns encourages reformulation, rather than innovation that can improve patient outcomes. So what to do? They make several suggestions, such as requiring the FDA to issue notices about reformulations, especially since this can be obscured if a product name does not change. What else? Payers should be urged to employ cost effectiveness analysis; pharmacists and state lawmakers could allow generic switching at bioequivalent doses, and physicians should question minor dosing changes to branded drugs.

But their big proposal would eliminate what they call the “moral hazard” of the 30-month delay in generic launches that are triggered by lawsuits filed by brand-name drugmakers seeking thwart generic rivals. “The FDA could require that all drugmakers seeking approval for NDAs involving a new formulation or dose of a previously approved molecule must resolve any outstanding patent infringement lawsuits concerning the original drug before their application is approved. Such a law would allow the FDA to approve these NDAs at the same time as ANDAs involving older formulations,” they write.

“Establishing a mechanism that approves branded reformulations and generics simultaneously would allow drugmakers to compete for patients on a level playing field. If the formulations are equivalent, then the price will determine the choice. If a new formulation offers a demonstrated advantage, then it may justify a higher price. In this approach, branded drugmakers are protected from invalid challenges to their intellectual property because the original formulation’s exclusivity is preserved until the litigation has been resolved and the new branded drug is approved.”