Gilead Sciences, Inc. (Nasdaq: GILD) is taking an unusual risk with its next generation of HIV prevention: it is preparing manufacturers to supply a medicine before the company knows whether the investigational regimen will clear its pivotal clinical and regulatory hurdles. On September 16, Gilead expanded existing royalty-free voluntary licences with six manufacturers to include a once-yearly intramuscular formulation of lenacapavir for pre-exposure prophylaxis, even though the Phase 3 PURPOSE 365 study remains underway and the regimen has not been approved by any regulatory authority. The agreements cover 120 high-incidence countries, primarily low- and lower-middle-income markets.
The six partners are Dr. Reddy’s Laboratories Limited, Emcure Pharmaceuticals Limited, Eva Pharma for Pharmaceutical Industries, Ferozsons Laboratories Limited, Hetero and Mylan Laboratories Limited, a Viatris subsidiary. These are not merely distribution agreements: the strategy is intended to give manufacturers more time for technology transfer, production preparation and supply planning before a potential approval. Gilead selected the companies partly for their ability to manufacture complex sterile injectable products, an important requirement if once-yearly lenacapavir eventually becomes a large-scale prevention option.
The decision creates a compelling pharmaceutical-development question. Conventional drug economics encourage companies to wait until clinical risk has fallen before committing extensively to manufacturing, registration and market-building. Gilead is deliberately doing some of the opposite because the cost of waiting could be measured not only in unused production capacity but in years of delayed HIV prevention.
Why is Gilead preparing once-yearly lenacapavir before PURPOSE 365 has reported?
Manufacturing long-acting injectable medicines is not something a generic producer can begin immediately after a regulatory approval. Processes must be transferred, validated and scaled; equipment and sterile-production capacity must be prepared; quality systems need to satisfy regulators; and national registration and procurement processes can take additional time.
Gilead learned that lesson while preparing twice-yearly lenacapavir. Its original voluntary licences with the same six manufacturers were signed in October 2024, before global PrEP regulatory filings had been completed. The company says technology transfer was completed within approximately three months, allowing partners to begin manufacturing preparations substantially earlier than they could have under the traditional sequence of approval first and generic development later.
That strategy is now being pushed one development stage further. The once-yearly formulation remains investigational, yet generic partners can begin work while PURPOSE 365 proceeds. If the study fails or regulators ultimately reject the regimen, some of that preparation may never generate commercial returns. If the programme succeeds, however, manufacturers could potentially be far closer to supplying low-cost versions when countries are ready to introduce the product.
This is essentially an attempt to exchange clinical-development risk for access speed. Gilead and its manufacturing partners accept the possibility of doing preparatory work for a medicine that never reaches the market in order to reduce the possibility that a successful medicine spends several additional years waiting for manufacturing capacity.
What exactly does PURPOSE 365 still need to prove?
The once-yearly programme should not be confused with the twice-yearly formulation already approved for HIV prevention. PURPOSE 365 is evaluating an investigational intramuscular formulation designed to maintain lenacapavir concentrations for an entire 52-week dosing interval. The Phase 3 open-label study is focused on pharmacokinetics, safety and tolerability, with a central objective of determining whether one annual dose maintains drug concentrations associated with HIV prevention across the full year.
ClinicalTrials.gov currently lists the study as active but no longer recruiting. Gilead completed recruitment earlier in 2026 and has indicated that an update is expected in 2027. The company has previously discussed a possible 2028 launch if development and regulatory review proceed successfully, although that timeline remains contingent on results and regulatory decisions.
That pharmacokinetic question matters enormously. Extending a six-month medicine to 12 months is not simply a matter of giving more of the same drug. The formulation must release enough lenacapavir to maintain protective exposure without creating unacceptable concentration peaks, injection-related problems or a prolonged period of low drug levels toward the end of the dosing interval.
The consequences of inadequate exposure could be particularly important with HIV prevention. Someone receiving an annual injection may reasonably assume that protection lasts for the promised period. A formulation therefore needs a highly reliable pharmacokinetic profile rather than an average concentration that looks adequate across a study population.
Why does twice-yearly lenacapavir give Gilead confidence to move this early?
The once-yearly programme is not starting from an unproven molecule. Lenacapavir already has an unusually strong prevention evidence base through the PURPOSE 1 and PURPOSE 2 Phase 3 trials of the twice-yearly injectable formulation.
Those trials found that at least 99.9% of participants receiving twice-yearly lenacapavir remained HIV negative across diverse populations. Longer-term follow-up presented in 2026 continued to show high efficacy, high adherence and no new safety signal: Gilead reported more than 7,178 person-years of follow-up from PURPOSE 1 and more than 5,295 from PURPOSE 2. In their open-label extensions, scheduled injection adherence remained 96% and 92%, respectively.
The United States Food and Drug Administration approved twice-yearly lenacapavir for PrEP under the Yeztugo brand in June 2025, making it the first U.S. HIV prevention option offering six months of protection per dosing cycle. The World Health Organization subsequently recommended twice-yearly injectable lenacapavir as an additional PrEP choice, specifically highlighting how long-acting options could address daily adherence, stigma and healthcare-access barriers.
PURPOSE 365 is therefore asking whether an already validated antiviral mechanism and prevention strategy can be extended to an even longer dosing interval. That is still a meaningful clinical risk, but it is very different from building global manufacturing capacity around a molecule whose efficacy in HIV prevention has never been established.
Would one injection a year really be meaningfully different from two?
Mathematically, the difference appears small: two healthcare encounters become one. Behaviourally and operationally, that difference could be significant.
Daily oral PrEP can work extremely well when taken consistently, yet real-world protection depends on people initiating treatment and continuing it as required. Barriers can include stigma associated with keeping HIV prevention pills at home, difficulty attending clinics, unstable living circumstances, competing health priorities and simple medication fatigue. WHO specifically identifies adherence, stigma and healthcare access among the problems long-acting prevention can help address.
Twice-yearly administration already reduces 365 potential daily adherence decisions to two scheduled treatment encounters. Once-yearly administration would halve those encounters again.
For health systems operating in geographically dispersed populations, one annual administration could also affect logistics. Fewer visits mean fewer appointments, injections and opportunities for patients to fall out of the prevention pathway between doses. Clinics could potentially protect more people using the same clinical workforce, although annual dosing would also require reliable systems for identifying when each person is due to return.
Longer duration can introduce a different risk: missing an annual appointment could create a much larger gap than being several days late with a daily medicine. Reminder systems, HIV testing protocols and follow-up procedures therefore become more important rather than less important as dosing becomes less frequent.
Why is global access already the central issue rather than an afterthought?
The epidemiological need remains substantial despite decades of progress against HIV. UNAIDS estimates that 1.2 million people acquired HIV globally during 2025 and 41 million people were living with HIV. Although new infections have fallen sharply from their historical peak, progress remains far short of global targets.
The prevention gap is particularly striking. UNAIDS reported that only around 3.9 million people used PrEP during 2024 against a target of 21.2 million people using PrEP at least once during the year. That means scientific efficacy is not the principal remaining constraint: a medicine can work extremely well and still have limited population effect if too few people can access or continue using it.
Gilead’s 120-country licensing programme attempts to address that second problem while development is still underway. The company is prioritizing regulatory work across 18 countries that together account for roughly 70% of the HIV burden within the voluntary-licence geography. Those markets include South Africa, Kenya, Uganda, Nigeria, Tanzania, Zambia, Zimbabwe, Thailand, Vietnam and the Philippines.
The practical significance is that a successful once-yearly product would not necessarily need to repeat the traditional sequence in which wealthy markets receive a pharmaceutical innovation first while generic supply chains begin years later.
Has the early-access model actually worked for twice-yearly lenacapavir?
There is already evidence that some of the preparatory strategy translated into faster deployment. The Global Fund said in September 2026 that twice-yearly lenacapavir had reached lower-income markets unusually quickly and described its rollout as a departure from the long delays historically associated with antiretroviral innovations.
By September, Gilead said lenacapavir for PrEP was available in 10 countries in sub-Saharan Africa. Its partnership with the United States government and the Global Fund now aims to reach up to three million people through 2028 under a no-profit supply programme while generic manufacturing expands.
Gilead has separately reached an agreement with the Pan American Health Organization to create another access pathway for twice-yearly lenacapavir across Latin America and the Caribbean, including countries that were not part of the original 120-country generic licensing territory. Reuters reported that the regional framework encompasses markets including Brazil, Mexico and Argentina.
That does not mean the access problem has been solved. Procurement budgets, national approvals, health-worker capacity, HIV testing, injection infrastructure and community acceptance all remain potential bottlenecks. Generic manufacturing removes only one barrier, albeit an important one.
Could generic competition undermine Gilead’s own commercial opportunity?
The licensing strategy deliberately separates high-income commercial markets from many high-incidence resource-limited markets. Gilead retains the ability to generate branded revenue in markets such as the United States while supporting royalty-free generic competition across the 120 licensed countries.
The financial results show why the company can afford to pursue both objectives. Gilead’s HIV portfolio generated $5.69 billion of second-quarter 2026 sales, up 12% year over year. Yeztugo itself produced $232 million in second-quarter sales and $397 million during the first six months of 2026 after only entering the U.S. market in June 2025.
This makes lenacapavir strategically unusual. It is simultaneously a global-health intervention and an increasingly important commercial growth platform.
Gilead is also developing several dosing formats around the molecule. In addition to twice-yearly injectable prevention and investigational once-yearly intramuscular dosing, the company has an FDA filing under review for once-weekly oral lenacapavir for PrEP. The broader objective appears to be creating a prevention portfolio in which people can choose among daily, weekly and very long-acting approaches rather than forcing one dosing model onto every population.
What could still go wrong with the once-yearly strategy?
The most obvious risk is pharmacokinetic failure. PURPOSE 365 could show that protective concentrations cannot be maintained consistently for 52 weeks, that variability between patients is too great or that the intramuscular formulation introduces tolerability problems that outweigh the convenience of annual dosing.
Regulatory authorities could also demand additional efficacy or safety evidence. Even though lenacapavir’s antiviral activity is established, approving a new formulation and dosing interval requires evidence that patients receive adequate protection throughout the claimed period.
Resistance is another important consideration in long-acting PrEP. Drug concentrations can decline slowly after an injection, potentially creating a pharmacological “tail” in which exposure becomes insufficient for reliable prevention but remains high enough to exert selective pressure if HIV infection occurs. WHO’s lenacapavir guidance specifically identifies resistance as an area requiring continued monitoring as long-acting PrEP scales.
Manufacturing preparation therefore remains a calculated gamble rather than evidence that the programme will succeed. Gilead itself states explicitly that once-yearly lenacapavir has not been approved anywhere and that its safety and efficacy have not yet been established.
Why could this strategy become a model for other pharmaceutical launches?
The conventional pharmaceutical-access sequence is structurally slow. A company completes trials, receives approval, launches its branded medicine, negotiates in additional countries, signs licences where appropriate, transfers manufacturing technology and eventually waits for generic production to reach scale.
Every stage reduces risk for the manufacturer, but the stages accumulate years.
Gilead is overlapping several of them. Clinical development, technology transfer, manufacturing preparation, country planning and community engagement are occurring partly in parallel.
This model cannot be applied blindly to every medicine. Preparing manufacturing for an entirely unvalidated Phase 3 asset could waste substantial capital. It becomes more rational when the underlying molecule already has extensive safety, efficacy and manufacturing experience and the new programme primarily extends formulation or dosing.
Lenacapavir fits that profile unusually well. The drug already has commercial HIV-treatment and prevention experience, Phase 3 prevention efficacy is established for six-month dosing, and generic partners have experience working on its injectable manufacturing process.
If PURPOSE 365 succeeds, the question will be how much time Gilead’s early licensing decision actually saves. A rapid transition from regulatory approval to scalable generic supply would provide an unusually concrete measure of whether pharmaceutical access can be engineered before the medicine reaches the finish line.
What does investor sentiment say about Gilead’s HIV strategy?
Gilead Sciences shares closed at $150.11 on September 18, down modestly for the session but more than 22% higher from the beginning of 2026, according to market data reported after Friday’s close. The stock had finished September 17 at $150.89, only about 4% below its 52-week high, after rising 2.17% during that session.
It would be inappropriate to attribute those moves specifically to the once-yearly licensing announcement. Gilead’s valuation reflects its broader HIV franchise, oncology pipeline, acquisitions, earnings and other catalysts.
The underlying commercial numbers nevertheless explain why long-acting HIV remains central to investor sentiment. Total HIV sales reached $10.72 billion during the first half of 2026, compared with $9.68 billion a year earlier, while rapid Yeztugo uptake is adding a new growth engine alongside the much larger Biktarvy franchise.
A successful annual PrEP formulation could therefore do two things simultaneously: strengthen Gilead’s long-duration HIV growth platform in commercial markets and expand the addressable public-health impact of lenacapavir in regions carrying the greatest burden of new infections.
Could once-yearly lenacapavir change the definition of adherence?
For decades, adherence in HIV prevention largely meant remembering to take medication frequently enough. Long-acting medicines are changing the question from whether someone can adhere every day to whether health systems can reliably bring that person back once or twice a year.
That is not automatically easier. It transfers responsibility from individual pill-taking toward appointment systems, procurement networks, community outreach, testing services and dependable medicine supply.
Yet the scale of the change could be substantial. An annual injection would mean a person could receive HIV prevention protection during one healthcare encounter and not need another administration for approximately 12 months if the investigational formulation performs as intended.
Gilead is preparing six generic manufacturers for that possibility before PURPOSE 365 has delivered its answer. The obvious interpretation is that the company is confident in lenacapavir. The more important interpretation is that it is trying to remove manufacturing delay from the critical path before regulators have anything to approve.
If PURPOSE 365 fails, the strategy will look premature. If the study succeeds and affordable annual PrEP reaches high-incidence countries far faster than previous pharmaceutical innovations, the bigger story may not be simply that HIV prevention became once yearly. It may be that part of the pharmaceutical industry’s access timetable was finally moved before approval rather than after it.
