Lenacapavir could be produced for $40 a year: 1000-fold lower than current US price for treating MDR HIV

Polly Clayden, HIV i-Base

Lenacapavir for PrEP could be produced by generic manufacturers at a price of $35–40 per person per year – according to data presented at AIDS 2024.

An analysis, led by researchers from Liverpool University, Department of Pharmacology and Therapeutics, UK and Howard University, Chemistry and Pharmaceutical Sciences, Washington DC, US, reported that lenacapavir active pharmaceutical ingredients (API) could achieve pricing of $25,000/kg, potentially decreasing to $10,000/kg or less with R&D investment and increased demand. [1]

With the costs of formulation, vials and profit margins, using standardised algorithms and Cost-Plus (cost+) pricing, mass production of generic lenacapavir, could be affordable as PrEP in low-income countries.  .  

But this would require the originator manufacturer (Gilead Sciences) to provide voluntary licences for lenacapavir, which have not yet been agreed. [2]

Over the past several years, cost+ pricing and voluntary licensing has enabled over 30 million people to receive antiretrovirals for HIV treatment in low-income settings. If it was similarly affordable, twice-yearly lenacapavir PrEP could substantially reduce the current rate of 1.3 million new HIV cases a year.

Lenacapavir is currently far too expensive for poor countries. It is sold for treatment in high-income countries at the eye-watering price of up to $44,819 pppy.

According to the researchers, it is a complex small molecule with a Cost-of-Goods (COG) largely dependent on the API. But lenacapavir is a low-dose drug (approximately 2 grams/person-year).

For the analysis, they questioned whether lenacapavir PrEP could realistically achieve $100 pppy and subsequently $35–40 pppy, with cost+ pricing and guaranteed purchases of 1 million (launch estimate) and 10 million (year 2 estimate) treatments per year. This represents approximately 2,000 kg and 20,000 kg of API.

They targeted API pricing of $25,000/kg and $10,000/kg to enable these COG. They noted that there are very limited data available for lenacapavir API pricing, and the originator’s cost basis is very different from that for generic production.

The researchers obtained current lenacapavir API and Key Starting Materials (KSM) costs from export databases (Panjiva and The Trade Vision LLC). Routes of synthesis (ROS) were analysed to project a COG for initial and increasing demand. They estimated cost+ prices with scale-up to produce sufficient doses for 1 million then 10 million treatment-years and compared this with current national list prices.

Lenacapavir API is currently exported for $64,480/kg on 1kg scale. This analysis and quotes for KSM/API support that $25,000/kg is achievable for lenacapavir API, with a committed demand of 2,000 kg/A.

These methods have predicted previous generic prices for HIV, HCV and TB drugs.

The researchers noted that an API COG of $10,000/kg will require substantial changes to the ROS. Bioequivalence trials and R&D for a better synthesis are needed. But, they concluded that $10,000/kg seems achievable with R&D investment at suppliers and 20MT/A volume demand. At these API COG, target pricing for the finished product ($93 and $40 pppy) can likely be met. This would translate to $93 million to treat 1 million people and $400 million to treat 10 million people.

Importantly, these prices require voluntary licences and competition between multiple generic suppliers. Gilead has not yet agreed lenacapavir voluntary licences with the Medicines Patent Pool.

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Unsurprisingly these data also attracted a lot of attention from the media – including Channel 4 and the Guardian in the UK.

At the moment, Gilead is charging over $40,000/year for lenacapavir as a component to treat people with HIV multi-drug resistance (MDR) in the US, Europe and Australia. This is similar to differences in the price of ART in the US compared to generic ART in low-income settings, so it is a realistic goal and expectation.

Although the company has issued a statement on voluntary lilensing of lenacapavir, but this does not include any details about when generics could be made available, target prices or countries included in their licence. 

The researchers analysed Gilead’s voluntary licence for TAF and the implications of a similar voluntary licence for lenacapavir.  They identified four major problems: 

1. The Gilead voluntary licence for TAF excludes key regions of the world where HIV is growing the fastest: North Africa, the Middle East, South America and Central Asia.  
2. The Gilead voluntary licence for TAF includes some countries with higher GDP per capita (eg Malaysia) while excluding countries with lower GDP (eg Morocco, Egypt).  
3. There are key populations in excluded countries with HIV incidence higher than in the PURPOSE-1 trial (2.41%).  
4. Gilead is conducting the PURPOSE-2 trial in Thailand, Brazil, Mexico, Peru and Argentina – only Thailand was included in previous agreements. It is not clear whether this is a violation of the Declaration of Helsinki.  This includes an obligation to ensure that the population of every country that participates in research are able to access any treatment that comes from these studies. This is specifically to prevent drugs being developed in countries where research is less expensive that are then priced at unaffordable levels for these countries.

The researchers also highlighted Gilead’s $114 billion profit since 2001 (and its use of tax havens and other tax loopholes).

Gilead need to ensure that lenacapavir can become available for $40 per person-year in all LMICs.  This would cover 83% of the world’s population, where 95% of HIV infections are happening.  This call is supported by the head of UNAIDS: ‘It is concerning that Gilead’s latest announcement seems to mention neither upper-middle income countries, where people cannot afford anything like lenacapavir’s current $42,250 price tag, nor a commitment to work with the UN-backed Medicines Patent Pool. Without these safeguards, it cannot be assured that this game-changing medicine will reach all those who need it.” 

The major generic companies need to be given a clear signal that development of low-cost lenacapavir should be started.  They need to be told that there will be funding available to support the production of one million person-years of lenacapavir, for a price less than $100 per person-year. 

Very importantly, the voluntary licence from Gilead should allow the generic companies to lower their prices to the levels which could be affordable to countries and the major donors.  Gilead should not set minimum prices at which generic lenacapavir is sold.  This would then allow competition between generic companies, leading to progressive reductions in the price of lenacapavir to the levels predicted in this analysis.  This has already happened with the voluntary licenses for ARVs to treat HIV, allowing progressive reductions in prices.    

References

Hill A et al. Lenacapavir: the need for affordability to realise potential. AIDS 2024, 22–26 July 2024, Munich, Germany. Late breaker abstract LB 46.