A generic pre-exposure prophylaxis (PrEP) option would greatly expand coverage among vulnerable populations and may well be the most cost-effective and safe option.
A generic pre-exposure prophylaxis (PrEP) option would greatly expand coverage among vulnerable populations and may well be the most cost-effective and safe option, investigators with Massachusetts General Hospital (MGH) and the Yale School of Public Health reported Monday at the virtual Annual Conference on Retroviruses and Opportunistic Infections (CROI 2020).
Access to PrEP is a cornerstone of the United States’ plan to end the HIV epidemic by 2030. Until last year, however, only 1 US Food and Drug Administration— (FDA) approved option existed—emtricitabine/tenofovir disoproxil fumarate (F/TDF; Truvada, Gilead Sciences).
But in October 2019, the FDA approved emtricitabine/tenofovir alafenamide (F/TAF; Descovy, Gilead Sciences) for use in men who have sex with men (MSM) and trans- gender women after it was found to be noninferior to F/TDF in the DISCOVER study, with comparably high drug tolerability and reported improvements in markers of renal and bone safety in MSM, although the full data have not yet been published.
Having more than 1 FDA-approved option available addresses 1 hurdle to PrEP access, but cost is another. With patent protection for F/TDF set to expire in 2020, cheaper generic formulations are expected later this year.
With so much about access to PrEP hinging on cost, a team of investigators is delivering the results of a cost-effectiveness analysis that set out to examine how the potentially improved safety profile of F/TAF over F/TDF might translate into observable clinical benefits. The research team also calculated estimates of the premium that one should be willing to pay for the benefits of switching from F/TDF to F/TAF. The data were virtually presented in a late-breaking poster at CROI 2020.
“The question ultimately was, ‘In the context of generic [F/TDF], is [F/TAF] cost effective and how much are we willing to pay for what they are advertising as benefits or less toxicity associated with that?’” Rochelle P. Walensky, MD, MPH, chief, MGH Division of Infectious Diseases and a professor at the Harvard Medical School, and presenting author of the study, told Contagion®.
Investigators relied on statistics from previous studies of people with HIV and data from an age-stratified population of 123,610 US MSM to compile safety data for F/TAF and F/TDF in order to forecast fractures, ESRD cases, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) over 5 years.
To determine the maximum price differential for F/TAF (currently $16,600/year, Federal Supply Schedule) over generic F/TDF for the cost-effectiveness analysis, the research team purposely exaggerated adverse clinical and economic outcomes of generic F/TDF and calculated conservative estimates for F/TAF.
“The whole point of this was to make [F/TDF] look bad and [F/TAF] look good, so we included really extreme bone and renal outcomes, and we gave no bad outcomes to F/TAF, which are now sort of coming into play…looking like there may be some increased lipid abnormalities, there may be some increased weight gain associated with [F/TAF]…we excluded all of that,” Walensky said.
Over the 5-year period included in the analysis, F/TAF averted 2101 fractures and 25 cases of ESRD for the 123,610 MSM receiving PrEP, with an ICER of more than $7 million per QALY. Assuming a 50% discount rate for generic F/TDF ($8300 per year) and the notion that society would be willing to pay up to $100,000 per QALY, investigators estimate the maximum fair price for F/TAF to be $8670 per year.
For patients (>55y) at highest risk of fracture, the ICER for F/TAF exceeded $3 million/QALY and the maximum justifiable price was $9020/year, according to the study results.
“I am concerned that…when [F/TDF] goes generic, this is a golden opportunity for us to blanket PrEP in the places that need it, and we'll have a lower cost drug to be able to reach really high-risk populations that have not been able to be on PrEP because of its costs,” Walensky told Contagion®. “I'm worried that the advertising will undermine the use of [F/TDF] and prevent this golden opportunity from taking hold.”
Investigators concluded that F/TAF justifies a markup no greater than $750 over generic F/TDF in the US. The team acknowledged the statistically significant differences in surrogate markers between F/TDF and F/TAF, but determined that, without evidence of clinical significance, there should be no urgency in switching PrEP regimens.
“If the manufacturer succeeds in driving out generic [F/TDF], then PrEP expansion in the United States could stall and the current aggressive [F/TAF] promotion campaign could actually end up causing more avoidable HIV transmission than it ultimately prevents because people don't have access to PrEP,” Walensky said.
The late-breaking poster, “F/TAF VS F/TDF for PrEP: How Much Is ‘Better’ Worth?” was virtually presented Monday, March 9, 2020, at CROI 2020.