Josh Bloom: Me-too? Says who? (Medical Progress Today)

A small study recently conducted by Abbott, a major pharmaceutical company, seems to indicate that they have discovered the Holy Grail of hepatitis C therapy–not only curing the disease, but also doing so without the use of interferon.

This is both an enormous medical advantage, and also serves as a good example of why those who use the term “me-too” drugs in a pejorative sense to describe second or third generation medicines have no idea what they are talking about.

As I noted last year, scientists at Abbott seemed to be on the cusp of being able to duplicate the AIDS cocktail approach for hepatitis C–and then some–having advanced both a protease inhibitor and a polymerase inhibitor to the point where it was reasonable to run trials with the intent of eliminating interferon from current hepatitis treatment regimens. (Interferon, which must be given intravenously, is exceedingly difficult for patients to tolerate, causing severe depression, flu-like symptoms, nausea and fatigue, forcing many patients to discontinue treatment.)
The trial results were nothing short of astounding.

When given a four drug cocktail, patients who had not been previously treated showed an astounding 95 percent cure rate (being virus free 6 months after cessation of therapy). In more difficult cases, where patients had already tried, but failed other therapies, 47 percent of these people (previously considered virtually untreatable) were still be cured. Interferon was not used at all. Is this innovative? After all, there are already two HCV protease inhibitors on the market from Vertex and Merck. So why keep going? Well, as it turns out, there are plenty of reasons, despite the constant braying of perennial critics like Marcia Angell of the Harvard School of Public Health. Angell, and others, who criticize so-called ‘me-too’ drugs as being non-innovative are displaying their ignorance about pharmaceutical matters. The second or third drug in a new class is often superior to the original. This can result in enormous medical advantages, despite what vocal critics wrongly maintain.

The HCV discovery model closely followed that used to discover the HAART (highly active antiretroviral therapy) drugs that revolutionized the treatment of HIV. The prototype HAART drug was Invirase (saquinavir), an HIV protease inhibitor (PI) launched by Roche in 1995. This marked the beginning of a decade of medical advances that were so remarkably successful that AIDS has mostly become a manageable chronic illness, largely out of the headlines.

But it sure wasn’t Invirase that was responsible. Even though Invirase worked, all sorts of problems, including gastrointestinal (GI) toxicity and poor bioavailability (meaning little of the administered dose was effectively circulating in a patient’s bloodstream), plagued it. As a result, possibly the most important and innovative new drug in decades isn’t even used any more.

But there are 9 other PIs available, and they sure as heck work. During the ten-year span in which these “me-too” drugs were being introduced, some were better–more potent and less toxic, each of these giving HIV a good stiff kick in its own way.

Does Dr. Angell really believe that we would have been better off without the ninth (and now preferred) HIV PI? Or how about the fifth (and most potent) non-nucleoside reverse transcriptase inhibitor (NNRTI), or the fifth nucleoside reverse transcriptase inhibitor? Because the medicines from this group of “me-too drugs” make up all of the preferred HIV cocktails at this time–the same cocktails that have not only tamed AIDS, but are now so good that they can prevent transmission from HIV-positive males to uninfected females 96 percent of the time, as demonstrated by studies last year in Africa. If you’re in the Ivory Tower neighborhood, maybe you should ask Dr. Angell whether drugs that are putting a huge dent in two of the most important viral infections in the world, AIDS and hepatitis C, and the companies that discovered them, should be deemed useless, along with the tens of millions of lives that they save, just because they are “me-too” drugs. Patients fighting HIV and hepatitis C know that the world would be far worse off without these medicines. What do you think?

Me too.

Josh Bloom is the director of chemical and pharmaceutical sciences at the American Council on Health and Science and a contributor to MedicalProgressToday.com.

ACSH