Team Metabolic Health
In June, Gilead Sciences announced impressive early results from its PURPOSE 1 trial, which showed 100 percent efficacy of lenacapavir in preventing new HIV infections among cisgender women in Sub-Saharan Africa. Lenacapavir is being investigated as an injectable antiretroviral medication that can be taken once every six months as preexposure prophylaxis (PrEP) to prevent HIV. This is a marked shift from current PrEP options, which are only available as a once-daily pill or a bimonthly injection.
Once again, the HIV community finds itself at a scientific breakthrough moment. And once again, it remains an open question as to whether it will also prove to be a breakthrough moment for equitable access.
We have been down this road before. It was not so long ago that the very same drug manufacturer released similarly jaw dropping clinical trial results first for Truvada and then Descovy, the first two medications approved for the prevention of HIV; it led to widespread speculation of the end of HIV as an epidemic. And yet, more than a decade after the first approval for PrEP in the United States, we still see significant disparities in getting PrEP to communities of color and cisgender women in the US.
Health care advocates are already concerned that past will once again be prologue when it comes to this new PrEP modality, and there is pressure on the company to make commitments that could change all too predictable outcomes on disparate outcomes.
The $40,000 Question
The big question of course will be the price set for lenacapavir’s PrEP indication in the US. We already have some insight here. In May 2019, Gilead received Food and Drug Administration (FDA) approval for a limited HIV treatment indication for lenacapavir for individuals for whom other HIV treatment regimens have not worked. The drug is sold under the brand name Sunlenca, which Gilead launched with a list price of $42,250 per year. To put the Sunlenca price tag in context, the list price of Gilead’s leading brand-name oral medication for PrEP, Descovy, comes in at about $26,000 per year. The bimonthly injectable PrEP option made by Gilead’s competitor, ViiV Healthcare, comes in at a comparable $23,000 per year.
There is no reason to think that as the indication of lenacapavir expands to PrEP, Gilead will back down from its initial high price. And again, we don’t need to guess here, we need only look at past actions. The pricing strategy that Gilead used to set the whopping $1,000-per-pill list price for its curative treatment for hepatitis C was fully explicated in a congressional oversight report, which found that Gilead’s goal was “maximizing revenue, regardless of the human consequences.”
To be clear, the list price is and has always been a bit of a fiction. With the availability of rebates and discounts and low-income assistance programs, few payers or even consumers will ever pay close to that amount. But it does matter. The list price sets the ceiling from which the complex set of drug distribution players in the US negotiate a lower price. Start high and even with discounts, we’ll end high. For a drug with such public health significance as PrEP, the high list price also hamstrings the ability of state and local public health departments that perennially struggle with anemic budgets—some of whom qualify for discounts and some of whom do not—to purchase the drug and get it out to uninsured, low-income, and vulnerable populations.
Other innovative purchasing strategies, such as a subscription model in which safety-net programs pay manufacturers a set negotiated amount for unlimited access to a drug, may be another consideration for PrEP. Subscription models have gotten some traction as a way for state Medicaid programs to cover costly hepatitis C curative treatments, but much more work has to be done to assess how a subscription model might be applied to PrEP, where the volume is lower and where there are multiple effective regimens, including low-cost generics, on the market.
Finally, the high list price locks us into fragmented delivery from the very beginning. Low-income individuals without insurance will be dependent on manufacturer patient assistance to help them access lenacapavir. Those programs will only provide access to the drug and not any other services people need to actually take the drug, including the recommended HIV, sexually transmitted disease, and other testing recommended to safely take PrEP. So instead of a public health program that is able to provide integrated access to PrEP services—including the medication—consumers will have to navigate a web of disparate programs to patch together all the services they need.
As we’ve seen with numerous other new-to-market drugs, a high list price for lenacapavir for PrEP will profoundly limit access for millions of uninsured Americans—a group that is disproportionately Black, Brown, and transgender and gender nonconforming. As noted above, the price point forecloses a public health response to PrEP, forcing individuals to jump through complex hoops to cobble together access. The decision on price made now could set the stage for more than a decade of inequitable access; Gilead has indicated in its most recent 10-K filing (page 7) that it expects lenacapavir to remain on patent and face no significant competition until 2037.
But Wait, Does Research And Development Justify A High Price?
Developing a new drug is an expensive endeavor. And indeed, high price tags are often justified by pointing to the immense costs of research and development. To be fair, Gilead undoubtedly invested in its PURPOSE trials, which have been far more comprehensive than the trials the company oversaw to secure a PrEP indication for Descovy, for which Gilead primarily conducted research among White gay and bisexual men and completely excluded cisgender women and transgender men.
But the cries that high prices are necessary for innovation seem somewhat disingenuous when they are rarely backed by transparency around the funding mix that goes into research and development of any one drug. And such claims deserve scrutiny when researchers have recently shown that lenacapavir could be made for less than $40 per person each year.
Past, again, may be prologue here. According to a Senate Finance Committee report on the development and marketing of Sovaldi, the first curative therapy for hepatitis C, “Gilead failed to provide costs attributable solely to the development of” its blockbuster hepatitis C cure despite repeated requests from Congress. The company from which Gilead acquired sofosbuvir estimated that the final Phase 3 studies would cost only $125.6 million, nowhere near an amount that would justify a $1,000-per-pill price tag. Following the December 2013 FDA approval, Gilead recouped its research costs and then some with $10.3 billion in 2014 sales of stand-alone sofosbuvir along with $2.1 billion in 2014 sales for Harvoni, a single tablet regimen of sofosbuvir combined with another direct-acting antiviral.
Recent research has also unearthed a very different investment story supporting the research and development for Gilead’s first approved PrEP medication, Truvada, finding that the federal government invested $143 million in the research leading to Truvada’s approval, far more than initially estimated and undermining Gilead’s justifications for steep price increases for Truvada following its July 2012 FDA approval as PrEP.
To be fair, developing breakthrough medications requires investment, and manufacturers should have incentives to embark on the long and arduous process of drug development that more often than not leads to a lot of failures before success. However, we should interrogate assertions that any policy aimed at identifying a fair price will imperil research and development incentives. Researchers have directly contradicted this assertion, modeling the impact of federal drug pricing reform and finding that the impact on new drugs coming to market is minimal.
What Can We Do Differently?
There is always hope we will learn from our past mistakes and do things differently the next time around. Advocates and academics alike have been calling for a federally funded national PrEP program to ensure widespread access to PrEP, particularly for un- and underinsured individuals. President Joe Biden included the program in his last three budget requests to Congress; it would provide the infrastructure necessary for the government to work meaningfully with Gilead to come up with an access strategy for lenacapavir at a price point that would work for a public health response. Should that come to pass, the US could really see the potential of this innovation for communities other than cisgender White men.
But even in a scenario in which the government steps in to work with Gilead to solve the access problem for uninsured populations, this pricing will create the same challenges for insured populations that have always existed in the US. Insurers will be absolutely disincentivized to encourage new PrEP users to access lenacapavir, particularly with affordable daily oral generic options at less than $20 per month. And with a price point for lenacapavir $10,000 to $15,000 above Descovy per year, we can anticipate payers’ strong resistance to even transitioning existing PrEP users over to lenacapavir. Even with a US Preventive Services Task Force Grade A for PrEP, which because of an Affordable Care Act (ACA) provision requires most private insurance plans to cover PrEP without cost sharing, there is no mandate for private insurance plans to cover every formulation of PrEP. Efforts are underway to improve insurance compliance with the ACA preventive services requirements for PrEP in general, but that advocacy faces an uphill road when Gilead is able to set whatever arbitrary starting price point it wants.
Another concern is that as new products, such as lenacapavir, come online, fullcourt marketing efforts may undercut the nascent market for generic oral forms of PrEP, which are safe, effective, and at less than $1 per pill, high quality but dirt cheap. This is exactly what happened when Gilead’s new oral PrEP regimen was approved the year before its first brand-name project went generic.
In the US, newer is often automatically dubbed better. And while the clinical trial results for lenacapavir are certainly impressive, it is not at all clear that the future of PrEP should be to push everyone onto long-acting brand-name products. Given the dismal uptake during these first few years of Apretude, the ViiV long-acting injectable for PrEP, it is also unclear if the market for long-acting products is quite as large as manufacturers say it is. At the end of the day, choice of the PrEP product that works best for the individual is the gold standard. What makes that choice possible is a fair price.
In the face of seemingly intractable drug access challenges in this country, there is still always the potential for an alternative future here. We can envision a scenario in which Gilead—perhaps facing significant pressure from the US advocacy community and the US government—commits to working with existing public health programs and, eventually, a national PrEP program to set a public health price point for lenacapavir to ensure a simple, transparent, and intuitive pathway for uninsured populations. This would be a new, bold approach—not a repeat of past charitable and donation programs that fail to provide an integrated approach to PrEP delivery. Instead, it would be a true, significantly lower price point that empowers public programs and health departments to come up with simple and comprehensive financing and delivery mechanisms that are highly accessible for end users. Only then will we stop repeating the same pattern in which the bang of a big scientific breakthrough is followed by the whimper of inaccessibility.
Credit: healthaffairs.org