In the news ... 2006 archive

Third Time is the Charm

January 30, 2006

Drug makers Bristol-Myers Squibb and Gilead Sciences recently announced positive results in their attempt to develop a single pill, once-a-day anti-HIV drug regimen. The new pill being developed will combine BMS’s NNRTI Sustiva (efavirenz) and Gilead’s NRTIs Emtriva (emtricitibine, FTC) and Viread (tenofovir, TDF).

The announcement stated that the companies were able to show that their combination pill achieved roughly the same levels of drug in the blood as taking the drugs separately. This is called bioequivalence.

Earlier attempts to co-formulate these drugs were unable to demonstrate bioequivalence. These earlier attempts came when they mixed all three drugs in one pill, much like Combivir or Truvada.

Faced with two failed attempts at mixing the drugs, the companies chose to layer the drugs—keeping each component separate while combining them in to one, multi-layered pill. This strategy finally achieved the goal of combining these three widely used anti-HIV drugs in to a single pill regimen.

This is good news for people with HIV for two reasons: simplification and cooperation.

The past few years have seen little in the way of novel drug development, with only one wholly new kind of drug approved (Fuzeon, enfuvirtide) along with newer versions of older classes of drugs, like Aptivus (tipranavir) and Emtriva (emtricitabine). Perhaps the most significant change in the world of anti-HIV drugs has been the drive toward simpler drug regimens. Faced with an increasingly crowded marketplace, pharmaceutical companies have been focusing on drugs and drug combinations that are easier to take, either by reducing the number of pills taken daily or reducing the number of times a day pill are taken. In some cases, both goals have been achieved.

The likely approval and marketing of this combination of Sustiva and Truvada (Trutiva? Sustivada?) marks a milestone in this drive toward simplification. Where once even the simplest anti-HIV drug regimen involved 10 or so pills, some people with HIV may soon be able to take a single pill, one time a day.

In reality it won’t be such a dramatic shift for people currently taking the drugs separately as it will only be a change from two pills once daily to one pill one once daily. Nonetheless, it does represent a significant moment in anti-HIV drug treatment.

The second and more remarkable story here is the unprecedented cooperation between rival drug companies. Combining multiple drugs in one pill is nothing new. In HIV there are currently four such products (called fixed-dose combinations) on the market—Combivir, Epzicom, Trizivir and Truvada. The difference is in all the previous cases, one company was combining two or three of their own drugs in to one pill. In this case two companies have managed to work cooperatively to combine their drugs in to a single pill.

A second recent development may also affect the use of the new fixed dose combination of Sustiva, Viread and Emtriva. Researchers announced the results of a study that compared the regimen containing Sustiva once daily plus Combivir (Retrovir + Epivir) twice daily against a regimen containing Sustiva + Viread + Emtriva, all once daily. The combination of Sustiva and Combivir is one of the most popular regimens in use today. However, study results showed a statistically significant advantage for the people receiving the alternate combination of Sustiva, Viread and Emtriva. After 48 weeks, 80% of the people receiving the alternate regimen (Sustiva + Viread + Emtriva) had viral loads below 50 copies, compared to 70% of those receiving the standard regimen (Sustiva + Combivir). Those on the alternate combination also had a higher gain in CD4+ cell levels (198 cells vs. 158 on the standard regimen. The study followed 511 people who were starting therapy for the first time.

What does this mean for people making their decisions about therapy, especially people just starting treatment? While the study shows clear advantage for the alternate regimen (Sustiva + Viread + Emtriva), both regimens performed reasonably well. It’s also important to note that any single study may not provide the final word on comparisons of two different regimens. Still, taken at face value, this study argues for using the alternate regimen rather than the older, standard regimen. This advantage will be boosted further when the single pill, fixed dose combination of Sustiva + Viread + Emtriva becomes available later this year.

The ball is now in GlaxoSmithKline’s court. They either need to demonstrate, through another study, that their regimen is not inferior (as shown in this study), or they may wish to concentrate their efforts on a different regimen. Studies are underway comparing Sustiva + Epzicom (Ziagen + Epivir) to other regimens. This combination replaces the older drug Retrovir with a more potent, newer one, Ziagen. While this may result in a more potent regimen overall, it also brings more worrisome side effects associated with the use of Ziagen and requires more careful monitoring by physicians.

Competition and cooperation in the pharmaceutical industry seems to be working to the benefit of people with HIV.