Drug Background

In August 2022, Gilead announced that the European Commission (EC) has granted marketing authorization for Sunlenca (Lenacapavir), an innovative treatment for adults with multi-drug resistant HIV infection. The treatment works in combination with other antiretroviral(s) when it isn't possible to construct a suppressive antiviral regimen otherwise. 

By December 2022, Gilead received FDA approval for Lenacapavir, presenting it as an HIV-1 capsid inhibitor available in tablet form for oral use and as an injection for subcutaneous use. Sunlenca, in tandem with other antiretrovirals, stands out as a twice-yearly treatment option for heavily treatment-experienced adults suffering from multidrug-resistant HIV-1 infection.

Target Indication

Strides in combination with antiretroviral (ARV) therapy (ART) for HIV-1 have enabled durable suppression of viral replication, leading to improved immunologic function, slowing disease progression, and enhancing life expectancy. While most individuals with HIV-1 have benefited from well-tolerated once-daily therapy, leading to a significant reduction in HIV-related morbidity and mortality, a subset continues to experience virologic and immunologic failure, highlighting the ongoing demand for newer therapies for individuals demonstrating multidrug resistance (MDR).

For managing MDR HIV, key agents are primarily boosted protease inhibitors like darunavir and 2nd generation integrase inhibitors such as Dolutegravir, employed alongside combination regiments, featuring recycled nucleoside analogs. Recently approved treatments specifically for MDR HIV include Ibalizumab and Fostemsavir. Hence, the requirement for ART remains significant with 28.7 million people on ART treatment out of an estimated 38.4 million people living with HIV globally as of year-end 2021.

Formulation and Dosing

Lenacapavir is available in injectable (solution) and oral (tablets) forms. The prescribed dosing strategy can be one of the following:

- Option 1: Initial dosage for adults comprises 927 mg (2 vials) injection and 600 mg (2 tablets) on Day 1, followed by 600 mg (2 tablets) on Day 2. The regimen is then sustained with a 927 mg (2 vials) injection every 6 months.

- Option 2: A second approach prescribes 600 mg (2 tablets) daily on Days 1 and 2, followed by 300 mg (1 tablet) on Day 8, a subcutaneous injection of 927 mg (2 vials) on Day 15, and then maintenance with a twice-yearly injection.

Market Potential - A Proposed Economic Analysis

The target patients for Lenacapavir are adults with heavily treatment-experienced HIV-1 infection and multidrug-resistant HIV-1. According to the World Health Organization (WHO) and other relevant sources, as of the end of 2021, 28.7 million people globally received ART out of the estimated 38.4 million people living with HIV. Approximately 0.84% of these patients are categorized as having tightly multidrug-resistant strains (MDR).

Given that Lenacapavir may be the only remaining effective treatment for these patients, coupled with their existing willingness to use ARVs, we project an uptake of this drug at 70%, which is likely underestimated. Consequently, this results in an estimated global target patient population of 168,756 willing to use Lenacapavir for treatment.

Demand Projections

With 168,756 patients, the demand for dosing options is as follows:

- Dosing Option 1: Requires 4 vials and 4 tablets in the first year, followed by 4 vials per year for maintenance.

- Dosing Option 2: Requires 4 vials and 5 tablets in the first year, followed by 4 vials per year for maintenance.

Based on these dosing options, the estimated demands in the first year are:

- 675,204 vials

- 675,204 tablets (Option 1)

- 843,780 tablets (Option 2)

For the annual maintenance demand, the estimate stands at 675,204 vials.

With the reference price on Drugs.com (the cost for Sunlenca oral tablet 300 mg is around $3,432 for a supply of 4 tablets (300 mg tablet), and for subcutaneous solutions, the price is around $20,543 for a supply of 2 * 1.5 milliliters), the revenue ceiling is estimated to be 7.515 to 7.659 billion USD in the first year and 6.935 billion USD annually for maintenance.

In terms of Lenacapavir Sodium API demand, around 515.38 kg to 566 kg will be needed in the first year, with approximately 312.87 kg required for annual maintenance.

Reference

https://www.who.int/news-room/fact-sheets/detail/hiv-drug-resistance

https://www.drugs.com/price-guide/sunlenca

Bajema, K. L. et al. Substantial decline in heavily treated therapy-experienced persons with HIV with limited antiretroviral treatment options. AIDS 34, 2051–2059 (2020).

King, J., McManus, H., Kwon, A., Gray, R. & McGregor, S. HIV, viral hepatitis and sexually transmissible infections in Australia: Annual surveillance report 2022. http://handle.unsw.edu.au/1959.4/unsworks_81131 (2022) doi:10.26190/SX44-5366.

Temereanca, A. & Ruta, S. Strategies to overcome HIV drug resistance-current and future perspectives. Front. Microbiol. 14, 1133407 (2023).