TWN Info Service on Intellectual Property Issues (Nov25/02)
13 November 2025
Third World Network

Indian regulator declines local Phase-III clinical trial waiver for Lenacapavir

New Delhi, 13 Nov (Chetali Rao and KM Gopakumar) – India’s medicine regulatory agency’s expert committee has declined Hetero Lab Ltd’s application to waive two studies for the manufacturing and marketing of generic Lenacapavir for the prevention and treatment of HIV.

The  Subject Expert Committee (SEC) of the Central Drugs Standard Control Organisation (CDSCO) turned down Hetero’s application for the grant of permission to manufacture and market long-acting Lenacapavir 300mg tablet. The minutes of the meeting note that Hetero’s proposal was supported by justification for waivers for a Phase III (local) clinical trial and for a bioequivalence (BE) study.

Hetero is among the six generic manufacturers that have been provided a royalty-free voluntary license by Gilead Sciences to make and sell generic Lenacapavir.

Rule 75 of the New Drugs and Clinical Trials Rules (2019) provides a significant provision for waiver of local clinical trials in India. Rule 75 states that:

“The local clinical trial may not be required to be submitted along with the application referred to in sub-rule (1) if,—

(i) the new drug is approved and marketed in countries specified by the Central Licencing Authority under rule 101 and if no major unexpected serious adverse events have been reported;  Under this, when a drug is already approved and marketed in certain “specified countries” namely the United States, United Kingdom, European Union, Japan, Canada or Australia, the Drug Controller General of India may waive the clinical trials. This waiver is granted subject to the generic manufacturer providing an undertaking to conduct a Phase-IV post-marketing study in India to monitor the safety and efficacy of the product concerned.  

While Hetero applied for a waiver based on the extensive clinical trials that were conducted globally on Lenacapavir, the committee noted that Hetero did not present any clinical study data on the Indian subset to prove that there was no substantial ethnic variability. The committee noted insufficient evidence to confirm the dose adequacy and safety/efficacy to approve the proposed dose requirement in the Indian population. This means that Hetero will have now have to carry out a local Phase III clinical study in the Indian population before it gets the approval for Lenacapavir.  However, the firm had already obtained permission for the conduct of a Bioequivalence study for export purposes from the Bioavailability (BA)/Bioequivalence (BE) division of CDSCO. The said BA/BE study is ongoing. Lenacapavir 300-mg tablets form a pivotal component of both the oral component/loading dose in lenacapavir regimens. 

Rejection Appears to Diverge from the New Drugs Clinical Trial Rules 2019

As reported earlier, Lenacapavir has not been registered in India and does not appear on the list of new approved drugs in India in 2024 and 2025.  An order of the Central Licensing Authority (CLA) dated 7 August 2024, issued under Rule 101 of the New Drugs and Clinical Trials Rules specifies that if a new drug is approved and marketed in the US, UK, EU, Japan, Australia, or Canada, local clinical trial waivers can be considered for the following five categories: orphan drugs, gene/cell therapies, drugs used in pandemic situations, drugs for special defense purposes, and drugs offering significant therapeutic advance over current standard of care..

Lenacapavir qualifies for consideration under Rule 101 for the following reasons:

• Lenacapavir has been approved in the specified countries and has also received marketing approvals from recognized regulatory agencies in the US, the EU, and other ICH member countries. It has also been recently recommended by the World Health Organization
• Lenacapavir is a significant therapeutic advancement over the current standard of care.  It addresses a significant, urgent health need among people living with HIV (PLHIV), where rapid access to new treatments is required.

There have been precedents where the SEC, with subsequent Technical Committee/Apex Committee concurrence, has recommended waivers under exceptional circumstances where sufficient global Phase III data existed and post-marketing surveillance conditions were imposed.  This includes drugs for HIV and TB.  In 2015, a waiver for local trials was also granted for an antiviral drug against HIV.

In pivotal clinical trials, including PURPOSE 1 and PURPOSE 2 studies, Lenacapavir demonstrated near-complete protection against HIV acquisition, with efficacy rates of 96–100% and a strong safety profile. In CAPELLA trials, it achieved high rates of sustained virological suppression in heavily treatment-experienced adults with multidrug-resistant HIV infection. Thus, there is strong global Phase III data for Lenacapavir (both treatment and prevention) across multiple countries and populations.

While the PURPOSE 1 study was conducted in South Africa and Uganda, PURPOSE 2 was conducted in the US, South Africa, Peru, Brazil, Argentina, Mexico and Thailand. Likewise, CAPELLA was conducted in Canada, the Dominican Republic, France, Italy, South Africa, Spain, Taiwan, Thailand, the U.S., Japan and Germany. If the foreign population were similar to the Indian population in key parameters (like HIV subtype and comorbidities), the need for a clinical trial would have lessened. In terms of HIV subtype, it has been found in a study that Southern Africa, Ethiopia, and South Asia (India) were dominated by subtype C, which constituted at least 97% of infections in each region in 2016–21. Also, given the comorbidity profiles, such as a high tuberculosis co-infection rate among both populations, foreign data were supportive of a waiver in India. Furthermore, the FDA label reports no clinically significant differences in the pharmacokinetics of Lenacapavir based on age, sex, gender, ethnicity, race or body weight, which reduces the need for a study in the Indian population. The global trial population was already diverse, including Latin American and African cohorts and this would have covered the variation axes.

Given India’s HIV burden (>60000 infections annually) and the goal of rapidly accessible prevention tools, public health arguments weigh in favour of an expedited approval for Lenacapavir. Lenacapavir represents a transformative advance in HIV prevention and treatment, offering the first and only twice-yearly injectable pre-exposure prophylaxis (PrEP),  a medication to prevent HIV. For people living with HIV, Lenacapavir provides a crucial option, especially for those with multidrug-resistant virus.​ Its long-acting formulation overcomes one of the most significant barriers in HIV care: suboptimal adherence to daily medications, particularly among populations burdened by stigma, social instability or limited healthcare access.

In the absence of a waiver, the timeline for the introduction of generic Lenacapavir in India will now be extended. Access delays will not only affect India but a large cohort of low- and middle-income countries (LMICs) covered under Gilead’s license – many of which depend on Indian generics for their supply. Granting this waiver would not only have expedited access to Lenacapavir for India’s 2.3 million PHLIV population but also positioned India as a global supplier, averting delays in LMIC rollouts. This regulatory hurdle postpones the potential public health benefits that timely, affordable generic Lenacapavir could offer.+