Protecting the Pipeline

LifeGuide [Treatment Horizons]

HIV drug development faces challenges
by Jeannie Wraight and Mariel Selbovitz, MPH

Triple and now quad drugs like Gilead’s Atripla and their new compound known as “the Quad” (presently submitted for FDA approval) make taking once-complicated HIV antiretroviral regimens much easier, but are also a double-edged sword, inadvertently making the development of new HIV drugs more difficult.

With the approval of triple and quad drugs, the U.S. Food and Drug Administration (FDA) has raised the bar on which HIV drugs will be approved by demanding new drugs be superior to what is already out there. This has lead to a contraction of the HIV pipeline from 100 drugs five years ago to sixty today, which will undoubtedly result in only a few reaching the goal of regulatory approval (and thus available for use by people with HIV), equating to much fewer options for those already resistant to the available meds.

The FDA is also demanding bigger and longer trials to help determine long-term side effects. Normally this would be a good thing but with the current financial climate, this requirement will decrease the number of potential HIV therapies even further as drug developers, many of which are small biotechnology companies, struggle to fund clinical trials through to regulatory approval.

Apricitabine (ATC) is just one therapy in development dramatically affected by the above factors. In October 2009 a clinical trial on ATC, a promising NRTI for patients who have developed resistance to multi-drug therapy, was halted, partially due to financial reasons. Two years later, the makers of ATC, Avexa, are pursuing efforts to conduct a Phase IIIb clinical trial. Unfortunately, private investment in the biotechnology industry has lapsed to near non-existence during the current financial crisis. Now with longer, more expensive trials required for regulatory approval and the growing trend within the FDA away from approval of single HIV drugs, the future of ATC, as it stands, is bleak despite the clear benefits patients would obtain from its use. Epzicom and Truvada were the last nucleoside reverse transcriptase inhibitors approved by the FDA in 2004.

As well as demonstrating high efficacy against wild-type HIV, the ATC data shows efficacy against HIV resistant to lamivudine, emtricitabine, and other nucleoside reverse transcriptase inhibitors. ATC is also active against HIV that is resistant to other types of drugs, such as integrase inhibitors, protease inhibitors, and non-nucleoside inhibitors. This makes ATC a valuable drug for people with extensive treatment experience who already have existing drug resistance. No serious adverse events were seen in clinical trials of ATC and side effects were minimal, including headache, diarrhea and nausea. ATC is a twice daily dosing drug. A Phase IIb study showed eighty-five percent of participants had undetectable viral loads at week ninety-six along with CD4 increases. No drug resistance to ATC was identified.

At the end of March 2011, the company received the go ahead from the FDA for their registration study of ATC and is currently looking at its options for taking the program forward towards approval.

As a single drug, ATC’s future is in jeopardy. The required dosage may be too high for some combinations with certain approved HIV drugs, making it difficult to be combined into one pill with those drugs. The push for drugs containing three or more drugs shouldn’t equate to the demise of single drugs which many HIV patients may need to complete a drug regimen.

Although there are currently forty-nine antiretrovirals currently in the pipeline, under the current regulatory conditions new drugs like ATC will most likely be few and far between. Despite significant advances in treatment, effective medicines are still needed. Government grants for mid- to late-stage HIV drug development by biotechnology companies is needed to fill in the funding gap, allowing for the financial conditions needed for the pipeline to move forward, providing people living with HIV who are already resistant to many of the currently available drugs and those who cannot tolerate some of them more options to build effective drug regimens.

Jeannie Wraight has been an AIDS treatment activist and HIV writer for over fifteen years. She lives in New York City.

Ms. Selbovitz is the AIDS Treatment Education and Policy Advocacy Program Director at Health People in the Bronx, New York, and chair of the Cornell ACTG CAB. She is a member of the AIDS Treatment Activists Coalition (ATAC) and the Campaign to End AIDS (C2EA). Ms. Selbovitz holds a Master’s in Public Health from Johns Hopkins University.

January 2012