Generic PrEP may present ‘golden opportunity’ for affordability
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Recommending the newly approved tenofovir alafenamide-emtricitabine, or F/TAF, for HIV prevention over a generic version of tenofovir disoproxil fumarate-emtricitabine, or F/TDF, that will be available later this year will not be cost-effective, even in patients at highest risk for adverse bone and renal outcomes from the old medication, according to findings from a cost-effectiveness study presented CROI and published simultaneously in Annals of Internal Medicine.
Researchers found that a markup for F/TAF of up to $370 over the price of generic F/TDF — $8,300 — may be justifiable, based on the differences between the two agents in regard to toxicity. As a result, given a generic option, the current price of F/TAF ($16,600 per year) would need to decrease by over $7,900 per year for F/TAF to meet “generally accepted standards of societal value.”
The FDA approved F/TAF in October of last year as a second option for pre-exposure prophylaxis (PrEP) in at-risk adults and adolescents. Gilead Sciences announced in May of this year that a generic alternative to F/TDF will be available in 2020 as the medication comes off patent.
“F/TDF should remain the first-line choice for virtually all ,” A. David Paltiel, PhD, of health policy and management at Yale School of Public Health’s public health modeling unit, told Healio. “The manufacturer has launched an aggressive campaign to undermine confidence in F/TDF and to encourage doctors to switch their patients to F/TAF before the patent on F/TDF expires. We find that the potential safety benefits of F/TAF are too small, too uncertain and way too expensive to justify a general switch.”
Paltiel and colleagues reviewed published to evaluate the of F/TAF for PrEP and identify the highest possible price premium for branded F/TAF over generic F/TDF. Paltiel told Healio that they intentionally overstated adverse economic and clinical outcomes of generic F/TDF by inflating rates of kidney and bone disease incidence, assuming all fractures and that cases of kidney disease would be irreversible and require dialysis.
The current population of MSM taking PrEP, when stratified by age, ranges from almost 49,500 individuals aged 24 to 34 years to nearly 10,000 among MSM older than 55 years.
After accounting for age-stratified risk and absolute numbers of patients, Paltiel and colleagues found that, over the 5-year period analyzed, compared with F/TDF, F/TAF would prevent 2,101 fractures and 25 cases of end-stage renal disease for the 123,610 MSM taking PrEP, with an incremental cost-effectiveness ratio (ICER) of $7 million per quality-adjusted life years (QALY). At a 50% discount for generic F/TDF ($83,000 per year) and a societal willingness to pay up to $100,000 per QALY, the maximum fair price for F/TAF was $8,670 per year. In adults aged 55 years and older, the ICER for F/TAF was more than $3 million per QALY and the maximum permissible fair price for F/TAF was $8,970 per year.
“Although clinical decision-making incorporates many factors in addition to cost and cost-effectiveness, these additions are welcome,” Carlos del Rio, MD, FIDSA, executive associate dean at Emory University School of Medicine, and Wendy S. Armstrong, MD, of Emory University School of Medicine, wrote in an accompanying editorial. “Walensky and colleagues’ study highlights the outsized cost of F/TAF compared with potential clinical benefits once F/TDF is generic and makes it clear that shifting to F/TAF as first-line PrEP for all cannot be universally recommended.”
Paltiel noted that the researchers were surprised at how “very little” additional clinical benefit F/TAF over F/TDF, as well as how small the fair price markup was for F/TAF over generic F/TDF.
“The imminent availability of generic F/TDF presents you with a golden opportunity to make affordable PrEP available to your most vulnerable patients,” Paltiel said. “The manufacturer’s aggressive marketing campaign could succeed in driving out the generic competition, stalling PrEP expansion and causing more avoidable HIV transmissions than it prevents.” – by Eamon Dreisbach
Disclosure: Paltiel reports grants from National Institute on Drug Abuse and NIMH during the conduct of the study. Please see the study for the other authors’ relevant financial disclosures.
Perspective
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Lynn T. Matthews, MD, MPH
In the middle of the COVID-19 pandemic, an important cost-effectiveness analysis comparing tenofovir alafenamide-emtricitabine (TAF/FTC, or F/TAF) and generic tenofovir disoproxil fumarate-emtricitabine (TDF/FTC, or F/TDF) for use as PrEP was published in Annals of Internal Medicine. This analysis is relevant as insurers and other payers consider whether covering F/TAF vs. generic F/TDF for PrEP (which is expected to be available later this year) is worth the higher medication cost.
Walensky and colleagues used published literature on U.S. MSM populations to evaluate the cost-effectiveness of these two combination preparations that prevent HIV infection among MSM and transgender women. Because F/TDF can lead to changes in bone mineral density and creatinine, the analysis incorporated data on fractures and end-stage renal disease (ESRD) based on 5 years of (continuous) use in MSM populations with an age distribution reflecting the population of U.S. MSM currently using PrEP. This analysis attempted to “favor” F/TAF at each decision point (ie, assuming all fractures are morbid hip fractures and a rapid rate of irreversible progression from early to end-stage renal disease). In addition, this analysis did not incorporate quantity or quality of life or cost decrements associated with the side effects unique to F/TAF, such as hyperlipidemia and weight gain).
F/TAF was associated with fewer fractures and cases of ESRD and a cost of approximately $7 million U.S. dollars per QALY. The maximum fair price of F/TAF was estimated to be $8,670 per year as opposed to the current estimated cost of $16,600 per year. Importantly, the authors note that “switching all patients to F/TAF-based PrEP could increase total expenditures by 5 billion U.S. dollars.” If the entire U.S. budget for HIV prevention were devoted to PrEP, approximately 11% of eligible MSM in the United States could be treated.
Some of the biggest challenges to daily oral PrEP are adherence and persistence; high costs promote neither. As the Affordable Care Act is increasingly gutted and many states continue to avoid expanding Medicaid, drug costs impact PrEP uptake. Gilead Sciences has provided a medical assistance program, but it’s not easy for providers or clients. We are all keen to embrace generic PrEP as we continue to eagerly await additional delivery options, including longer term injectables, implants and topical choices that work for men — and women. This careful analysis clarifies the limitations of F/TAF as a substitute for generic F/TDF and should guide providers, clients, payers and insurers in choosing which approved oral PrEP agent to prioritize. In an era where the limits of what our health care system can purchase are increasingly obvious, this analysis highlights how a nominal improvement in safety does not justify preference over a generic medication with excellent safety and efficacy for men and women.
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del Rio C, et al. Ann Intern Med. 2020;doi:10.7326/M20-0799.
Walensky RP, et al. Ann Intern Med. 2020;doi:10.7326/M19-3478.
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