The pre-exposure prophylaxis (PrEP) market for HIV is heating up.
Since 2012, emtricitabine-tenofovir disoproxil fumarate (FTC/TDF; Truvada, Gilead), which had annual sales of about $3 billion, has been the only PrEP available. Last year, the FDA approved FTC-tenofovir alafenamide (FTC/TAF; Descovy, Gilead) for PrEP, but it is not indicated for cisgender women, who are at risk from receptive vaginal sex.
Also, a generic version of FTC/TDF by Teva Pharmaceuticals is expected this fall.
“The looming question is how often patients and providers use the generic version for HIV treatment and prevention,” said Rochelle Walensky, MD, MPH, the chief of infectious diseases at Massachusetts General Hospital, in Boston.
An estimated 90% of patients who were taking Truvada have switched to Descovy for treatment. “However, the jury is still out as to how many patients will be switched to Descovy for prevention, especially with the availability of generic Truvada,” she said.
Gilead reportedly has priced the brand-name versions the same and is marketing FTC/TAF as a safer option. “Although the trials demonstrated that Descovy has slightly better biomarkers of renal and bone safety over Truvada, it is not clear if these translate into clinically meaningful differences in adverse events,” Dr. Walensky said, noting that early studies suggest increased weight gain and cardiovascular risk factors with FTC/TAF.
The initial FTC/TAF trial had surrogate markers for bone mineral density and renal toxicity, “but not true meaningful end points,” Dr. Walensky said.
“Nonetheless, for patients with HIV who are aging and might have comorbidities, there might be an indication for some of those patients to change from Truvada to Descovy,” she added.
Although FTC/TAF is considered safer for kidney and bone problems, “there may be some cardiovascular concerns with the newer drug,” explained Rodrigo Burgos, PharmD, a clinical assistant professor in the Section of Infectious Diseases Pharmacotherapy at the University of Illinois at Chicago College of Pharmacy. “Hence, at this stage, I do not believe we can definitively rule out using Truvada for PrEP.”
Until it is proven that FTC/TAF is more cost-effective than FTC/TDF for PrEP, “it is easy to understand why an entity would prefer to use the less costly option of Truvada,” said Dr. Burgos, who is also the co-author of the ArtClass column.
Similarly, because evidence of efficacy for FTC/TAF as PrEP is limited to specific populations like men who have sex with men, “having a single agent that is effective in all populations may add appeal to Truvada when making decisions on cost and public health,” Dr. Burgos pointed out.
On the other hand, FTC/TAF may provide a safer treatment option for patients with kidney or bone disorders. “Availability of safer medications is a win-win for both patients and health care providers, and should be the goal for every medication on the market,” Dr. Burgos said.
Dr. Burgos does not find it odd or suspect that Gilead is introducing a new drug for PrEP within one year of FTC/TDF becoming generic. “I do not find it any different than any other company bringing out a new product to the market after a current product’s patent protection expires,” he said. “It is not uncommon for a company to introduce newer and better products around patent expiration of a product.”
However, other people have taken exception to Gilead’s products. The federal government sued Gilead, seeking damages claiming infringement of Health and Human Services patents related to PrEP and that the company profited from research funded by taxpayers. There is also a patient-driven class action lawsuit against Gilead, claiming that it knowingly sold a product (FTC/TDF) that caused bone and kidney issues when it had a safer alternative (FTC/TAF) that it did not seek approval for until its patent was expiring.
Regardless, cost is not the top criteria for most prescribing clinicians, according to Dr. Walensky, who is also the vice chair of the HIV Medicine Association, so it was hard to predict who would recommend switching.
”As for clinicians embracing the generic PrEP medication, “providers do not generally revert to a previous drug because of costs and costs alone,” Dr. Walensky, said. “Thus, it is not entirely clear once Truvada goes off-patent and can be acquired much cheaper, how many practitioners will actually prescribe the generic version and how many patients will consider a switch.”
However, Dr. Burgos predicted generic FTC/TDF will be embraced by both patients and physicians. “Most patients do not like to change the medications on which they have been stable, specifically to a generic version,” he said. “However, any dislike is usually momentary and has not been an issue in the past when many other antiretrovirals have gone generic.
Dr. Walensky did acknowledge the clever marketing by Gilead. “I also believe it is an intentional move to dissuade clinicians from using generic Truvada,” she said. “There are published data about Descovy dating back to 2001.”
With more than 1 million people in the United States needing PrEP, public health interventions need to consider “whether putting people on a more expensive drug like Descovy versus generic Truvada will result in fewer people having access to PrEP, especially since we do not really understand or know the end game of Descovy’s safety profile,” she said.
Meanwhile in January, the New York City Department of Public Health and Mental Hygiene announced that its drug of choice for PrEP would remain FTC/TDF. “So I think there are numerous policymakers who understand these implications, despite the marketing efforts by Gilead,” Dr. Walensky said.
Big Challenges Ahead
The biggest challenge with any other PrEP agent, regardless of whether it is a brand-name or generic medication, “is identifying and reaching out to at-risk individuals and making PrEP available to them,” Dr. Burgos said. “Will the lower cost of generic Truvada actually translate to savings for society or extra services for our patients, or will only a handful of people benefit from that lower cost?”
David Condoluci, DO, MACOI, an infectious disease specialist, said FTC/TDF has made an important contribution to HIV care. “But the main concern with Truvada is long-term renal toxicity, specifically an increased risk of renal insufficiency from the original formulation of the Viread component,” said Dr. Condoluci, who serves as the senior vice president and chief patient safety and quality officer for Jefferson Health in New Jersey.
Despite the reformulation of the Viread component, “there remains the issue of too much lactic acid in the blood with either Descovy or Truvada,” he said.
With more than 1 million Americans needing PrEP, public health interventions need to consider “whether putting people on a more expensive drug like Descovy versus generic Truvada will result in fewer people having access to PrEP, especially since we do not understand or know the end game of Descovy’s safety profile,” Dr. Walensky said.
Drs. Condoluci and Walensky reported no relevant financial relationships. Dr. Burgos has worked on trials sponsored by GlaxoSmithKline and Merck.