Gilead plans European trial of twice-yearly HIV PrEP drug

Gilead Sciences has said it will soon start a clinical trial in Europe of its twice-yearly HIV injection Sunlenca for pre-exposure prophylaxis (PrEP), a potential successor to its big-selling Truvada and Descovy brands, which need to be dosed every day.

The PURPOSE 5 trial will enrol people in the UK and France who are HIV-negative, but at elevated risk of contracting HIV and, according to Gilead, focusses on groups that are “disproportionally affected by HIV and often underrepresented in clinical trials.” It will compare Sunlenca (lenacapavir) to Truvada (emtricitabine/tenofovir disoproxil fumarate) in people who are not already taking PrEP.

Sunlenca (lenacapavir), an HIV capsid inhibitor, is already approved in Europe, the US, and other countries as a twice-yearly treatment for people living with multidrug-resistant (MDR) HIV in combination with other antiretroviral drugs.

“HIV continues to be a public health threat across Europe, where, in 2022, more than 100,000 people were newly diagnosed with HIV,” said Gilead, which added, however, that estimates suggest “less than 15% of people in Europe who could benefit from PrEP are accessing PrEP options.”

The study is the latest in a series of trials exploring lenacapavir’s role as HIV PrEP. PURPOSE 1 is comparing the drug to Truvada in approximately 5,000 cisgender women in South Africa and Uganda, while PURPOSE 2 is recruiting 3,000 men who have sex with men, gay men, transgender men and transgender women, and gender non-binary people in Argentina, Brazil, Mexico, Peru, Puerto Rico, South Africa, Thailand, the US, and Vietnam.

PURPOSE 3, meanwhile, will study lenacapavir for PrEP among cisgender women in the US who are disproportionately affected by HIV, with a focus on Black women and other women of colour, and PURPOSE 4 involves people who inject drugs in the US.

Gilead is playing catch-up in the long-acting injectable PrEP category with GSK’s majority-owned ViiV Healthcare, which claimed FDA approval in late 2021 for Apretude (cabotegravir), an integrase inhibitor used for adults and adolescents at risk of sexually acquired HIV, followed by EU approval last month.

A key difference between the two drugs is that Apretude needs to be administered six times a year with an intramuscular injection into the buttocks, so needs to be administered by a healthcare professional, while lenacapavir is a subcutaneous injection that could be self-administered.

Apretude’s take-up to date has been fairly slow, with £41 million ($50 million) in sales last year and £36 million in the first half of 2023, and it is making a fraction of Truvada’s estimated peak PrEP sales of $2 billion before generics started to enter the market, as well as Gilead’s follow-up Descovy (emtricitabine/tenofovir alafenamide), which made $1.7 billion last year from sales across its uses as HIV PrEP and treatment.

Analysts have suggested that Sunlenca could eventually become a $4 billion blockbuster if it gets approval across all its planned indications, with PrEP a key part of that prediction.