Economically, the modest safety benefit of tenofovir alafenamide-emtricitabine () for HIV preexposure prophylaxis won’t justify paying thousands of dollars more for it when tenofovir disoproxil fumarate-emtricitabine ( ) becomes available as a generic in a year or so, according to a population level cost-effectiveness presented at the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers held a because of concerns about the spread of COVID-19.
Those benefits will translate to a health savings worth only a few hundred dollars over the likely generic price, said investigators led byand infectious disease physician and professor of medicine at Harvard Medical School, Boston.
In a press statement, Gilead, which makes both medications, said it “strongly believes that the analysis ... is flawed, leading to inaccurate conclusions that severely underestimate the value of Descovy. The method and validation of the models, incomplete clinical data analyzed and the assumptions around potential pricing associated with a generic alternative to Truvada ... are inadequate to enable a sufficiently robust analysis.”
The company did not go into details about what exactly might have been off about the analysis.
Approved in Oct. 2019, tenofovir alafenamide-emtricitabine (also known as F/TAF) is the first new option for HIV preexposure prophylaxis (PrEP) since tenofovir disoproxil fumarate-emtricitabine (F/TDF) was approved in 2012; F/TDF is going off patent soon.
Amid a robust marketing campaign, the new medication has already captured 25% of the PrEP market, and Gilead expects up to 45% of patients to switch to F/TAF before generic F/TDF becomes available.
That worries the investigators. “At the current FSS [Federal Supply Schedule] price of $16,600 per year,” a nationwide PrEP program that uses F/TAF “would consume the entire $900.8 million federal budget for HIV prevention several times over ... If branded F/TAF drives out generic F/TDF,” rates of PrEP coverage “could decrease, and F/TAF could end up causing more avoidable HIV transmissions” than it prevents. “Given the very small, albeit statistically significant, differences in surrogate [safety] markers, without evidence of clinical significance, there is no urgency and no reason to switch PrEP regimens now,” they said. Both medications were equally effective in preventing HIV transmission in Gilead’s head-to-head, but there was an a mean of about a 4 mL/min difference in estimated glomerular filtration rate at week 48 and about a 2% difference in hip and spine density at week 96, both favoring F/TAF. Marketing highlights those differences.
The investigators wanted to see how much they are worth, so they estimated savings from a possibly lower rate of bone fractures and renal failure with F/TAF and juxtaposed it with its cost and the anticipated cost of generic F/TDF at half-price, $8,300/patient-year.
They gave F/TAF the benefit of the doubt, skewing their model toward maximal harm and cost from F/TDF toxicity, and omitting the cost of increased lipid levels, weight gain, and other possible F/TAF adverse events.
In the end, they concluded that “the improved safety of F/TAF is worth no more than an additional $370 per person per year” over generic F/TDF based on toxicity differences. “
The team calculated that F/TAF would prevent a maximum of 2,101 fractures and 25 cases of end-stage renal disease among 123,610 U.S. men who have sex with men treated for 5 years. That translated to an incremental cost-effectiveness ratio of more than $7 million per quality-adjusted life-year, far above the $100,000 threshold considered acceptable in the United States.
“In the presence of a generic alternative, the current price of F/TAF would have to be reduced by over $7,900/year for F/TAF to satisfy generally accepted standards of societal value. If F/TDF can achieve the 75% price reduction that is commonly observed when generic competition ensues (that is, a cost of $4,150/year), the F/TAF price would need to be no higher than $4,520 to demonstrate value on the basis of cost-effectiveness,” the investigators said.
For older patients at unusually high risk for renal disease or bone-related adverse events, the switch from F/TDF to F/TAF would have greater clinical effect and benefit. Even in this population, however, it would be difficult to defend a price greater than $800 over the cost of the generic alternative,” they said.
“The message seems clear that the current cost of F/TAF does not justify wholesale conversion to F/TAF as the first-line agent for all PrEP-eligible patients,” saidand infectious disease professors at Emory University, Atlanta, in an . “For PrEP-eligible persons at low risk for fracture and renal disease, it is very hard to justify use of F/TAF knowing that F/TDF will soon be generic” (Ann Intern Med. 2020 Mar 10. ).
“Successful PrEP scale-up in other countries was made possible by drug costs that are less than $100/month in most countries. In the United States, without drastic reductions in the cost of PrEP, which may be achievable with generic F/TDF ... we will fail to avert otherwise preventable new HIV transmissions,” they said.
The study was simultaneously published online (Ann Intern Med. 2020 Mar 10.).
The work was funded by the National Institutes of Health and Massachusetts General Hospital. The investigators and editorialists didn’t have any industry disclosures.
SOURCE: Walensky RP et al. Ann Intern Med. 2020 Mar 10. .