January 24, 2012 2:42 pm
This article is provided to FT.com readers by BioPharm Insight—a news service focused on providing insight into the most price sensitive issues in the global pharmaceutical market. www.biopharminsight.com
Gilead Sciences’ (NASDAQ: GILD) once-daily Truvada pill has seen only tepid interest for adoption in the HIV prevention setting, despite treatment guidelines by the Centers for Disease Control (CDC), experts told Biopharm Insight. This is largely related to issues around feasibility, cost and historical evidence for other prevention strategies, which may not be remedied even with the FDA label Gilead is seeking, infectious disease experts said.
Last December, the company announced a supplemental NDA (sNDA) regulatory application for its currently marketed HIV drug Truvada, a potential therapy to reduce the risk of acquiring HIV, commonly described as pre-exposure prophylaxis (PrEP). Truvada has been approved since 2004 for use in combination with other antiretroviral drugs to treat HIV infection.
Truvada has not been approved yet as a preventative therapy in HIV.
Results from the Phase III iPrEx study reported in the New England Journal Of Medicine in December 2010 showed prophylactic effect from Truvada given orally among men who have sex with men (MSM). In January 2011, the CDC issued interim guidance on the use of PrEP in this population.
While HIV therapy is much more manageable than previously, with fewer pills and side-effects, experts in recent years have begun to initiate therapy in earlier stages of the viral infection, and most recently in uninfected individuals to prevent infection. While multiple PrEP studies have reported encouraging data, multiple hurdles to adoption still remain.
Slow uptake thus far
This news service reported in December 2010 that uptake of Truvada as an HIV prophylaxis therapy would likely be slow, as non-HIV specialists would largely be responsible for prescriptions. Infectious disease specialists reported few, if any, prescriptions in this indication, when interviewed by this news service.
The University of North Carolina division of infectious disease has not been prescribing PrEP, said Dr Christopher Hurt, clinical assistant professor. He added there has been some talk in the medical community that primary care providers and potentially ob-gyns would be responsible for PrEP prescription, similar to how they are responsible for oral contraceptives.
He noted in some urban areas, particularly San Francisco, Boston, New York and Washington, DC, with stronger healthcare settings for MSM, have probably been prescribing PrEP more frequently as they regularly see those individuals at risk of HIV infection. He noted his clinic had some discussion about offering PrEP to partners of current patients, but no decision was finalized. Those partners need to be in care somewhere, where potential side effects can be monitored, he added.
Another possible model is uninfected individuals having an initial consultation and prescription from an HIV provider and then going back to their primary care provider for regular HIV and renal monitoring – as a worsening of renal function has been seen with Truvada, said Dr Dan Kuritzkes, professor of medicine, division of infectious diseases, Brigham Women’s Hospital of Harvard University.
As there will be a mix of providers prescribing PrEP, it could take up to 10 years for it to really take hold among a general mix of providers, said Dr Mark Dybul, a science and policy expert at the O’Neill Institute for National and Global Health Law, Georgetown University.
Howard Jaffe, chairman of the Gilead Foundation, said the responsibility for educating patients about PrEP must be shared by healthcare providers, public health officials and community leaders, and Gilead intends to support outreach and educational efforts to ensure these groups are able to deliver accurate information to their patients/constituencies. The Gilead Foundation is a non-profit under Gilead focused on expanded access to care.
High cost in cash-strapped system
Some rough calculations revealed that about 44 patients would need to be given PrEP to prevent one infection, said Dr Dong Lee, assistant professor, infectious diseases, at Drexel University. He estimated this to cost about USD 500,000, when it costs USD 20,000 to treat one infected person per year. Lee added there has been much discussion of the feasibility of this on a real world basis, when other less expensive prevention measures like condom use exist.
Still, the number of patients needed to treat can vary by geography, as incidence levels vary, said Dr Craig Hendrix, professor of medicine, pharmacology and molecular sciences and epidemiology, Johns Hopkins University. In Baltimore where he practices, the number-needed-to-treat is somewhere between 500 and 1000 individuals, so PrEP might not make much sense in the region, he said. In other regions, where the number-needed-to-treat might be more in the range of 50-100, PrEP could make more sense, he said. This makes it more difficult for healthcare systems to make a coverage decision on PrEP, he added.
Further, it is unclear if the level of counseling that went along with the drug in the clinical studies is sustainable, confounding whether the same level of efficacy will be seen with real world use, said Kuritzkes.
There is also no mechanism like AIDS Drug Assistance Programs (ADAP) – which provides HIV drugs – or the Ryan White Act – which provides HIV care – for providing care to uninfected people if they do not otherwise fall under Medicaid, said Kuritzkes. This becomes a significant stumbling block for rolling out PrEP, especially in the populations where it could actually have a significant impact, he added.
He said he expects the PrEP market in the US will largely be a niche market of wealthier MSM who have the independent resources to access PrEP.
Jaffe said Gilead’s current patient assistance program was designed to ensure people living with HIV have access to treatment. Should Truvada for PrEP be approved by the FDA, Gilead plans to support access via demonstration projects, which will help Gilead evaluate the initial implementation and use of PrEP and, ultimately, better determine how best to support access to PrEP through the patient assistance program.
Balancing PrEP and Treatment as Prevention
The HPTN-052 study, presented at the International AIDS Society meeting in Rome in July 2011, demonstrated that early antiretroviral therapy (ART) in the infected partner among stable, healthy sero-discordant couples led to a 96% reduction of sexual transmission of HIV.
The impressive study results, referred to as “treatment as prevention,” beg the question of whether treatment of uninfected individuals, or treatment of those already infected, has a greater benefit, said Hurt.
HPTN-052 had more dramatic results than any of the PrEP studies, though not for surprising reasons, said Hendrix. HPTN-052 had a more potent drug strategy, using a full ART regimen, whereas Truvada is only two drugs, he noted. He added there has been some early modeling work about establishing a policy in a socialized system for government spending on individuals infected and those at risk. When most people know their HIV status, it is clearly more effective to treat everyone infected rather than those at risk – but recent CDC numbers indicate that well below 50% of individuals are being effectively treated, he said.
Still, there are individuals who may be at risk of HIV exposure where a partner’s status is unknown, or who cannot control the actions – or lack thereof – of their partners, said Kuritzkes. Dr Connie Cellum, professor of global health & medicine, University of Washington, and lead investigator of the Partners PrEP study, said no single strategy will meet the needs of all at risk groups. Similarly, Dr Dawn Smith, biomedical intervention implementation officer, National Center for HIV/AIDS Prevention of the CDC, whose group authored the interim guidance, said they have since discussed the HPTN-052 study in the context on PrEP. The CDC feels an obligation to make information about multiple prevention methods available so that people can access and use whatever prevention methods are best suited to their lives, she said.
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