Success rate for new ARVs entering phases II–III surpassed 32% from 2003–2011
U.S. ADAP Prescribing Practices Closely Match Recent ARV Guidelines
by Polly Clayden and Mark Harrington
As we were putting together the 2011 Pipeline Report this summer, we decided to look back at the previous years’ reports on anti-HIV drug development. Treatment Action Group (TAG) has been covering the antiretroviral (ARV) drug pipeline since our founding; in the past two years we have joined forces with HIV i-Base (UK) to deepen and broaden our coverage.
To preface this year’s Pipeline, we decided to look at the series of detailed pipeline reports since 2003. We wanted to examine several questions:
- Whether the HIV drug pipeline is drying up;
- What the success rate is for new ARV drugs entering phases II–III to assess the likelihood that current candidates will progress toward approval; and
- How rapidly which new drugs and combinations enter practice in one industrialized country, the United States.
The global ARV treatment market is estimated at $13 billion in market volume this year (Market Research News 2011), with most of the profits made in industrialized countries, while most of the people in need of treatment live in developing ones.
The past decade has indeed been a golden age of ARV drug development. Of the 30 new chemical entities approved by the U.S. Food and Drug Administration (FDA) to treat HIV infection since 1986, half (15/30) were approved in the years since 2003 (FDA 2011a). Thirty-seven drugs and fixed-dose combinations (FDCs) are FDA-approved for sale in the United States; a further 132 drugs and FDCs (including adult and pediatric formulations) are tentatively approved under the FDA’s generic registration program to facilitate global access through programs such as the President’s Emergency Program for AIDS Relief (PEPFAR) (FDA 2011b). Please see the data series from the TAG ARV pipelines dating from 2003 to the present. Download 
2011 Pipeline Table 1
The success rate for new ARV drugs and FDCs that have entered phase II or further studies since 2003 is an astonishing 32.6% (15/46). Most recently, in 2011, the FDA approved rilpivirine (Edurant), extended-release nevirapine (Viramune XR), and the FDC rilpivirine/TDF/FTC (Complera).
In the first quarter of 2012, Gilead is expected to file with regulatory authorities for approval of the integrase inhibitor elvitegravir, the pharmacokinetic booster cobicistat, and the FDC elvitegravir/cobicistat/TDF/FTC (“Quad”), with regulatory action likely later in 2012, which, if it leads to approval, would bring the success rate to 39.1% (18/46).
So much for those who say investing in HIV treatment is a bad bet.
Rapid implementation and uptake of new therapies provides rapid return on investment.
Another remarkable feature of the HIV treatment landscape is the rapidity with which new drugs and combinations are incorporated into the standards of HIV care in developed countries. In the United States, this process has been facilitated since the late 1990s by the establishment of the standing Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents and the Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children (http://aidsinfo.nih.gov/Guidelines/Default.aspx).
The Adult and Adolescent Guidelines Panel meets monthly by teleconference, once yearly in person (usually at the annual retrovirus conference CROI), and issues updated online treatment recommendations at least annually, with changes highlighted in yellow to make navigating the ever-changing treatment landscape easier. A review of data generously provided by the U.S. National Association of State and Territorial AIDS Directors (NASTAD) demonstrates the astonishing fidelity of U.S. AIDS Drug Assistance Program (ADAP) prescribing practices in 2009 to the most recent iteration of the U.S. HIV treatment guidelines. Download 2011 Pipeline Table 2
Among the many striking features of the 2009 ADAP reported data on ARV usage are:
- 75% of sales were for drugs recommended as preferred first-line antiretroviral therapy (ART) regimens in the federal guidelines (DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents 2009);
- Of the nine drugs and FDCs included among the U.S. first-line recommendations, eight were approved by the FDA in the past decade; just one (efavirenz) was approved in the 1990s;
- Two drugs approved in 2006 and 2007—darunavir and raltegravir, respectively—were approved by the FDA for first-line indications less than two years after initial recommendation in salvage patients;
- Both of those drugs soon after were included by the U.S. guidelines panel among the preferred recommended regimens for antiretroviral-naive patients; and
- Prescribing practice rapidly evolved to incorporate the newest data on the newest drugs.
These data demonstrate the effective interaction of research, regulation, normative guidelines, practice, and implementation in the United States, despite its highly fragmented health care system and the fact that those receiving treatment through ADAP are, by definition, not rich.
However, the fact that 8,785 individuals in 10 states are currently on waiting lists to receive treatment through ADAP reveals that the United States continues to be a global disgrace when it comes to universal access or health equity (NASTAD 2011b).
In any case, it is clear that HIV therapeutics has room for considerable improvement, and that improvements will be rapidly diffused and their investors will enjoy a substantial return on their investment.
We urge the World Health Organization (WHO) as well as national guidelines-defining groups in countries affected by HIV to urgently implement such forward-looking practices to ensure that people living with HIV everywhere have access to the best possible treatment options.
In next year’s Pipeline we look forward to documenting further progress.