New variants of existing HIV treatment drugs are rapidly replacing their older ones, but one mainstay is moving on to an even more important role as the regimen that prevents infection with the virus.
Combination medicines that include tenofovir disoproxil fumarate (TDF), which was approved by the FDA in 2001, are among the leading antiretroviral agents in HIV treatment. They include:
All have hit the blockbuster-level sales mark. All are marketed by Gilead, the heavyweight in the HIV drug market. A major reason for their popularity is that they have made HIV treatment so much simpler. What was once a complicated regimen is now a single pill.
But now Gilead has developed an improved formulation of tenofovir called tenofovir alafenamide (TAF). As a result, its TDF agents are slowly but surely ceding king-of-the-hill status to three new TAF products.
Genvoya (emtricitabine, elvitegravir, cobicistat, tenofovir alafenamide), the first regimen with TAF, was approved in November 2015. Last year, the FDA approved two additional TAF formulations, Odefsey (emtricitabine, rilpivirine, tenofovir alafenamide) and Descovy (emtricitabine, tenofovir alafenamide). Genvoya and Odefsey are considered complete therapy; Descovy is used in combination with other medications.
TAF is as effective as TDF but in much smaller quantities. The lower dose lessens the risk of kidney damage and bone mineral density problems, so new TAF combinations don’t need the TDF label warning about the risk of renal impairment and the need for creatinine clearance testing at the start of therapy.
Pre-exposure prophylaxis is practiced by about 80,000 people in the United States, says Erik Storholm, a Rand researcher.
But Gilead also has not-so-trivial business reasons for pushing the TAF drugs. The TDF patent for adult use expires in 2017 and in 2018 for pediatric use, so the new TAF drugs should help keep Gilead’s revenue from branded HIV drugs from petering out. HIV products account for about half of Gilead’s total annual revenue, and sales of its hepatitis C drugs—Sovaldi, Harvoni, and Epclusa—are slipping.
So far, Gilead seems to have played its cards well because sales of the TAF products are strong. First quarter 2017 sales for Genvoya were $769 million compared with first quarter 2016 sales of $158 million. Descovy’s first quarter 2017 sales were $251 million, putting it on track for blockbuster status this fiscal year. First quarter 2017 sales for Odefsey were in the same ballpark.
Express Scripts’ 2016 Drug Trend Report highlights the impact of Gilead’s switch from TDF to TAF products. Express Scripts’ total expenditure increase (trend) for 2016 in the antiviral category was 21.7%, which includes a 5.5% increase in utilization and a 16.2% unit-cost increase. Only 5.3% of HIV prescriptions were for generic drugs, and the average cost per script was $1,556. Express Scripts anticipates the trend to continue at about 20%.
The top five drugs by market share in Express Scripts’ book of business were Truvada, Atripla, Viread, Norvir, and Genvoya. Norvir is an Abbvie product; the other four are Gilead’s.
Drug price information published on the NIH’s AIDSinfo website indicate that the average wholesale prices of Gilead’s new TAF combination drugs were comparable to its TDF-based products as of April 2016.
Truvada, a TDF, was Gilead’s 2016 HIV sales leader, but this year the TAF drugs are cutting into its sales. But Truvada is getting a new lease on life as a preventive agent. It is the only drug approved to prevent HIV infections, and Truvada is the key pharmaceutical component of pre-exposure prophylaxis, which is aimed at preventing, rather than treating, HIV infection and transmission.
Truvada received approval for HIV prevention in 2012, eight years after its nod for HIV treatment. In two clinical trials, it demonstrated a 42% and 75% reduction in HIV infection and a 92% reduction in transmission in one of those studies. Those trials and others since have shown that adherence to Truvada as pre-exposure prophylaxis is the key to prevention. In fact, in one small study in which people were over 90% adherent, there were no infections.
Truvada for pre-exposure prophylaxis can be prescribed only to people who are HIV negative. Part of the reason for this approach is concern that if people who are HIV positive use Truvada for preventive purposes, they will unintentionally create HIV variants that are resistant to Truvada.
When the FDA approved Truvada for prevention in 2012, the FDA and Gilead took a cautious approach to its rollout, limiting use to high-risk individuals. The go-slow approach was understandable. Decades of funding for public education and promotion of safe sex practices were paying off. No one wanted to undo those public health achievements with an approach that might be misinterpreted as suggesting that a daily pill has replaced the need for other precautions.
Three years ago, the CDC’s HIV guidelines changed to include pre-exposure prophylaxis as an option. The CDC says pre-exposure prophylaxis is recommended as one prevention option for sexually active adult men who have sex with other men, heterosexually active men and women with HIV-positive partners, and adult injection drug users at substantial risk of HIV acquisition.
After the CDC guidelines came out, HIV clinics began telling the story of the potential of pre-exposure prophylaxis, and Gilead cranked up its marketing of pre-exposure prophylaxis. Truvada’s label now specifically mentions its use as part of pre-exposure prophylaxis for high-risk individuals.
Express Scripts provided Managed Care with valuable insights into its experience with pre-exposure prophylaxis. A company spokesperson told us that Express Scripts spends more money on Truvada than any other HIV medication. Most (60%) of Truvada users take the drug for treatment purposes, but Express Scripts says the number of people taking the drug for pre-exposure prophylaxis has nearly doubled in the last year.
Erik Storholm, PhD, a Rand researcher, says pre-exposure prophylaxis is practiced by an estimated 80,000 individuals. The NIH reported that the April 2016 average wholesale price of Truvada was $1,760 for a monthly supply of the 300mg/200mg dose. Truvada is covered as a preferred drug in many Express Scripts formularies, and Storholm says coverage is common in the plans of other pharmacy benefit companies. In addition, it’s available through AIDS clinics and public health programs. Gilead also has various copay and patient assistance programs.
Overall, the HIV/AIDS epidemic is tapering off. The CDC says there were approximately 37,600 HIV infections in 2014, down from 45,700 in 2008. But the overall picture glosses over some of the glaring differences in population groups. For example, black men now account for 45% of new cases, even though they make up less than 7% of the total U.S. population.
The challenge facing pre-exposure prophylaxis and HIV diagnosis and treatment continues to be in achieving equity across all populations. In June, the FDA granted Teva Pharmaceuticals approval for a generic version of Truvada including the indication for pre-exposure prophylaxis. A generic version of Truvada would presumably be less expensive. But there’s uncertainty about exactly when the generic will be available—and its price.
A report of the FDA’s approval on POZ.com, an HIV/AIDS news site, reports that the uncertainty may be tied to a patent dispute. Other drug manufacturers—Lupin, Cipla, and Amneal Pharmaceutical—are developing their own generic versions of Truvada.