Cabotegravir (CAB) is the only approved long-acting integrase strand transfer inhibitor (INSTI). In combination with the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV), it forms the only approved fully long-acting HIV treatment regimen. This regimen is currently approved by several national regulatory authorities for use in virologically suppressed adults with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine, administered monthly or every 2 months. Despite its benefits, including for use in LMICs, the injectable CAB+RPV regimen is currently not included in WHO guidelines for HIV treatment.

Compared to daily oral antiretroviral therapy (ART), CAB+RPV could support the improvement of adherence to treatment, achieve and maintain virologic suppression. However, there may be concerns about the suitability of the use of this regimen in specific populations with co-infections (see below). One key issue for implementation in resource-limited settings is that rilpivirine—not cabotegravir—requires a cold chain for storage. Additionally, rilpivirine’s low barrier to resistance raises concerns about the long-term effectiveness of the NNRTI class in case of clinical resistance to the drug.

For people living with both HIV and hepatitis B (HBV), switching from a tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF)-containing regimen—such as the widely used oral tenofovir/lamivudine/dolutegravir (TLD)—to dual regimens, including CAB+RPV, would remove the HBV-suppressive effects of TDF or TAF, potentially worsening HBV management in people living with both HIV and HBV. Furthermore, drug-drug interactions between CAB+RPV and tuberculosis (TB) treatments, such as rifampicin and rifabutin, pose additional concerns for individuals living with both HIV and TB.

Data indicate that people facing adherence challenges to daily oral treatment, who switched to long-acting injectable CAB+RPV experienced greater viral load reductions than those remaining on daily oral ART. More recently, findings from the CARES study in 3 countries in sub-Saharan Africa demonstrated that switching to CAB+RPV was non-inferior to continuing oral ART, with high rates of HIV-1 RNA suppression at week 96. This study marks an important milestone, highlighting the potential clinical feasibility and effectiveness of long-acting injectable HIV treatment in LMICs.

Long-acting cabotegravir for HIV PrEP was licensed to MPP in 2022. With RPV patents expected to expire in 2027, and the formulation of cabotegravir being the same for PrEP and for treatment indications, in least developed countries, the expansion of the ViiV-MPP licence for cabotegravir long-acting for PrEP to also cover the treatment indication, could open the possibility for generic CAB+RPV LAI in LMICs, and potentially in the future, to other cabotegravir-based long-acting regimens for HIV treatment, if companion drugs also benefit from appropriate access programs.

Patent & licence data for cabotegravir in LMICs

Cabotegravir and rilpivirine on LAPaL

Acronyms & abbreviations list

Lenacapavir is a capsid inhibitor with a novel mechanism of action, distinguishable from other currently approved classes of antiviral agents, as it inhibits HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes. Lenacapavir has received regulatory approvals in Europe and 10 high-income countries as a treatment for adults with multi-drug resistant HIV, intended for use in combination with other antiretroviral medications. It is also awaiting approval for use in the context of HIV prevention.

Lenacapavir primary patents have been filed or granted in several LMICs and are expected to expire between 2034 and 2037. Gilead also holds secondary patents that may provide exclusivity until 2038 in many LMICs. Gilead has signed bilateral voluntary licence agreements with six generic manufacturers, allowing for sales of lenacapavir for HIV prevention and treatment of heavily treatment-experienced adults with multi-drug-resistant HIV in 120 countries. LMICs beyond the licence territory will not have access to the generic products via these agreements.​

An approved long-acting companion medicine allowing for a fully long-acting lenacapavir-based treatment regimen is still missing, and lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies of potential fully long-acting HIV treatment regimens. Of notice, the current voluntary licence does not cover a broad treatment indication. Given the prominent role such regimens could play in the future, and remaining uncertainties surrounding lenacapavir’s future accessibility and affordability in LMICs for both treatment and prevention indications, including the possibility of expanding the geographical scope and indication of the licensing agreements, lenacapavir remains a priority for MPP. Two HIV treatment regimens currently stand out as priorities for MPP licensing: lenacapavir with either cabotegravir or islatravir. The possibility of the addition of a regional manufacturer in countries with high HIV prevalence in sub-Saharan Africa would increase health security and increase capacity.

Lenacapavir for PrEP

Lenacapavir is a candidate for long-acting pre-exposure prophylaxis (PrEP) through a twice-yearly subcutaneous injection, following an initial oral loading phase. Gilead has submitted marketing authorisation applications to EMA (for both EU MAA and EU-M4all) and to the FDA. Results from the PURPOSE 1 and PURPOSE 2 phase III trials have demonstrated high effectiveness in preventing HIV, with mostly mild injection site reactions such as pain, nodules, and indurations . Additionally, recent data confirm lenacapavir’s safety and efficacy in adolescents, broadening its potential impact on containing the HIV epidemic if rolled out extensively.

At CROI 2025, groundbreaking findings on new intramuscular formulations of lenacapavir were presented, featuring two single-dose injections designed for annual administration. These formulations were safe and tolerable in the study participants, and maintained plasma drug concentrations above the 95% effective threshold for at least 56 weeks, highlighting the feasibility of extending dosing intervals even further. If successful in follow-up trials, adjusted yearly injections could represent a significant shift in HIV prevention strategies. If affordable and accessible, this candidate could represent a very powerful tool to contain the global HIV epidemic. It is not known whether this formulation is captured under the Gilead voluntary licence for lenacapavir.

Lenacapavir for treatment

Lenacapavir is currently approved by several stringent regulatory authorities for the treatment of HIV-1 infection in heavily treatment-experienced adults whose current antiretroviral regimen is failing due to resistance, intolerance, or safety concerns. Lenacapavir’s low administration frequency and long-acting nature could offer a paradigm shift also in treatment.

A phase II clinical study investigated the efficacy of a weekly oral combination of lenacapavir and islatravir. The study demonstrated strong virologic suppression without negatively affecting lymphocyte counts. These results have prompted the initiation of two phase III trials , which are evaluating a weekly oral fixed dose combination of islatravir and lenacapavir in virologically suppressed persons living with HIV. The research supports broader efforts to develop more convenient, decentralized HIV treatment options that could improve access while supporting increased adherence.

Lenacapavir is also under investigation in combination with cabotegravir (with or without rilpivirine) for individuals with NNRTI resistance. A small case-series showed high rates of virologic suppression in people with HIV on a LEN+CAB regimen, highlighting its potential as a long-acting injectable option for people with limited treatment choices. However, additional research is needed to confirm safety, efficacy, durability, and resistance barriers. A multicentric clinical trial assessing the use of LEN+CAB for HIV treatment in comparison to standard of care is in planning stages.

Additionally, lenacapavir is being explored in combination with once-daily bictegravir as a possible simplified regimen for people with HIV who require complex treatment due to previous resistance or treatment failures.

However, accessibility remains a challenge—lenacapavir is not yet registered for the treatment indication in LMICs, limiting its availability to those who may benefit most from this alternative in a treatment regimen.

Patent & licence data for lenacapavir  in LMICs

Lenacapavir entry in LAPaL

Acronyms & abbreviations list

_{1 Priorities for antiretroviral drug optimization in adults and children report of a CADO, PADO and HIVResNet joint meeting (accessible here).}

MK-8527 is an investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) being developed for the prevention of HIV. MK-8527 shares mechanistic similarities with islatravir, offering the potential for high potency and a strong genetic barrier to resistance. MK-8527 is a promising clinical candidate for HIV PrEP, being evaluated for once-monthly oral dosing. The phase IIa study to assess safety, tolerability, and pharmacokinetics of oral MK-8527 once monthly was just completed, while a larger PK/PD study has just started. Of notice, a specific trial is also planned, evaluating the drug PK in breast milk and blood of breastfeeding individuals. MK-8527 primary patents with an expected expiry in 2034 have been granted to MSD in at least 35 LMICs and are pending in another 13 countries. Secondary patent filings are anticipated.

Islatravir is a first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTTI) that is not yet approved. After a temporary pause in clinical development due to safety concerns, Merck has resumed selected islatravir programs with close safety monitoring.

Recent phase III studies have demonstrated that islatravir, when administered as a once-daily oral treatment in combination with doravirine (DOR/ISL 100 mg/0.25 mg), is both safe and non-inferior to commonly used antiretroviral therapy (ART) regimens in virologically suppressed individuals with HIV-1.

Additionally, islatravir is being investigated as a fixed dose combination with lenacapavir as weekly oral treatment (see also above in the lenacapavir section). If successful, an oral long-acting HIV treatment could provide an important alternative, particularly in settings focused on decentralized service delivery.

Patents on islatravir compound and its use for treating HIV – owned by Yamasa corporation and licensed exclusively to MSD – were mainly filed in HICs and Mexico and were expected to expire on 24.03.2025. A patent family covering the use of Islatravir for the treatment or prophylaxis of HIV (dosing regimen less frequent than once-daily) owned by MSD includes patent applications filed in several LMICs countries/regions with an expected expiry in February 2037.

Patent & licence data in LMICs

Acronyms & abbreviations list

GS-1720 is an investigational once-weekly oral INSTI being evaluated for treatment in both treatment-naïve and switch populations of people living with HIV. GS-1720 is studied in combination with GS-4182, a new oral lenacapavir prodrug with improved bioavailability. Phase II/III WONDERS trials are currently underway using the GS-1720+GS-4182 combination.

If successful, a weekly oral HIV treatment could provide a valuable alternative for PLHIV.

Gilead primary patent applications on GS-1720 have been filed in about 47 LMICs with an expected expiry in 2042. Further secondary patent filings are anticipated.

GS-4182 is an investigational lenacapavir prodrug with improved bioavailability and potential for oral weekly administration. GS-4182 is studied in combination with GS-1720, a new oral INSTI. Phase II/III WONDERS trials are currently underway using the GS-4182+GS-1720 combination. In December 2022, Gilead filed three international patent applications covering lenacapavir pro-drugs, which may include GS-4182. Confirmation will be possible once the chemical structure of GS-4182 is available in the public domain. The expected expiry of the compound patents is 2042, and additional secondary patent filings are anticipated. If successful, a weekly oral HIV treatment could provide a valuable alternative for PLHIV.

Cabotegravir 4-monthly, also called CAB-ULA (ultra long-acting) is an  investigational longer-acting formulation of cabotegravir that demonstrates a pharmacokinetic (PK) profile supporting dosing intervals of approximately four months. This extended dosing schedule has the potential to reduce clinic visits and improve adherence. Early data suggest a favourable safety profile, with intramuscular (IM) administration being better tolerated than subcutaneous (SQ) injection. As a result, CAB-ULA IM dosed every four months is advancing into late-stage studies investigating its use for both HIV-1 PrEP and treatment.

For PrEP, the EXTEND 4M registration trial is evaluating a single IM injection of CAB-ULA at 1600 mg/3mL. The FDA has approved this registration strategy, based on PK bridging studies, without requiring an additional efficacy study. The trial was launched in December 2024 and is expected to reach its primary endpoints by Q3 2026.

For HIV treatment, a phase III registration trial is evaluating CAB-ULA combined with rilpivirine (RPV) at Q4M dosing, following the completion of phase I studies on multiple formulations.

Primary patents on cabotegravir have been granted in many LMICs and are expected to expire in 2026. A secondary patent on the 4-monthly formulation was published in March 2025. The corresponding international patent application is pending, and geographical coverage in LMICs is expected to be available by March 2026, with patents anticipated to expire in 2043.

Cabotegravir 4 monthly on LAPaL

Acronyms & abbreviations list

Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for use in combination with other antiretroviral agents for the treatment of HIV-1 in adult patients with no prior antiretroviral treatment history. It is being investigated for HIV treatment in combination with islatravir as once daily oral treatment. However, the evidence of clinical benefits over the standard of care is still unclear.

Primary patents on doravirine compound and its combinations with other anti-HIV agents have been filed in many LMICs and are expected to expire in 2031. In few countries, the patent term may be extended by another five years, until 2036. While bilateral voluntary licences have been granted to generic manufacturer for 86 countries, public information on such licences is limited. The existing licence for DOR may enable access to generics of DOR+3TC in 86 LMICs; however, the development status for licensed generic DOR versions is unknown.

Patent & licence data in LMICs

Acronyms & abbreviations list

This insert is a candidate tenofovir alafenamide/elvitegravir (TAF/EVG) insert fast-dissolving, bullet-shaped tablet for vaginal or rectal administration for on-demand HIV prophylaxis (both PrEP and post-exposure prophylaxis, PEP). The insert contains a co-formulation of antiretroviral drugs that dissolve upon insertion, preventing HIV replication locally. This candidate passed several phase I studies    and is currently collecting more data on safety and PK for both administration routes . It is awaiting to enter phase II to continue assessing safety and effectiveness. As this phase II study was planned in the context of the USAID-funded MATRIX project, the progress of this promising prevention candidate that could complement other existing tools is currently paused.

CONRAD have filed for patents on their TAF/EVG sustained release formulation for vaginal or rectal use in 7 LMICs, including South Africa. If granted, these would likely expire in 2039. If successful, this product could complement other PrEP and PEP options, serving clients of any gender for whom a discreet, user-initiated, event-driven HIV prevention method would be appealing. The manufacturing prospects indicate a potential low-price for quality assured generic versions if a voluntary licence agreement is reached.

Ulonivirine (previously known as MK 8507) is an orally-administered, non-nucleoside reverse transcriptase inhibitor being developed by MSD.

ulonivirine on LAPaL

Acronyms & abbreviations list

VH4524184 is a third-generation INSTI, with a superior resistance profile. It could be important in cases of future INSTI resistance.

VH4524184 is a phase II third-generation integrase strand transfer inhibitor (INSTI) administered by injection, with a superior resistance profile compared to second-generation INSTIs. It could be important in case of increasing DTG resistance. The chemical structure of VH4524184 is not available in the public domain. Similarly, no patent information is available yet, however patent filings are to be expected.

ViiV’s new capsid inhibitor demonstrated promising phase IIa data, with oral doses ranging from 25 mg to 250 mg every five days in ART-naïve individuals. By day 11, virologic suppression was observed. The drug is planned for development as an injectable long-acting (LA) therapy. The chemical structure of VH4011499 is not available in the public domain. Similarly, no patent information is available yet, however patent filings are to be expected.

These laboratory-made proteins emulate the immune system’s ability to counteract harmful pathogens, including HIV. Although still in the early stages of development, broadly-neutralising antibodies demonstrate significant potential for use as HIV post-natal prophylaxis (PNP), due to their favourable safety profile and the convenience they may offer through a single administration covering the peri-natal and breastfeeding period via intramuscular injection,,. Despite potential benefits, crucial clinical data on the efficacy of monoclonal antibodies for PNP remain lacking. Specifically, there is a notable gap in understanding whether a single monoclonal antibody could suffice for prevention. If multiple mAbs are necessary, the cost could become a significant concern, especially when compared to cheaper small molecules.

Beyond their use in postnatal prophylaxis, broadly neutralizing antibodies (bNAbs) are also being investigated for HIV cure strategies. The RIO study explored the use of two antibodies that can complementarily neutralize HIV through distinct mechanisms of action (3BNC117 and 10-1074, also known as teropavimab and zinlirvimab) in cis-gender men participants who accepted to stop their HIV-antiretroviral treatment, indicating that a one-time infusion of this antibodies combination could sustain viral suppression for over a year in some participants . While these findings remain preliminary, they highlight the broader therapeutic potential of bNAbs beyond postnatal prophylaxis.

Quabodepistat (previously known as OPC-167832) is a medicine with a new mechanism of action that has potent antituberculosis activity and a favourable safety profile. Despite premature termination of PAN-TB Consortium trials including quabodepistat - since the trial does not support the investigational regimens being able to achieve the trial objective of identifying a new regimen to treat tuberculosis in 3 months or less - Otsuka plans to study the drug with bedaquiline and delamanid in phase III trials. The primary patent on quabodepistat has been granted in more than 50 LMICs and is expected to expire in 2035. There are secondary patents on intermediates and combinations that may provide exclusivity until 2037-2039 in many LMICs.

Patent & licence data in LMICs

Acronyms & abbreviations list

Alpibectir functions through a unique mechanism that targets bacterial transcriptional regulators, activating novel bioactivation pathways for ethionamide (Eto). Eto is an older, well-known anti-TB drug, but its use at high concentrations is limited due to significant side effects. By enhancing Eto’s efficacy, alpibectir enables its use at lower, non-toxic concentrations, potentially improving its safety profile while maintaining therapeutic effectiveness. Alpibectir is in phase II. Primary patents on alpibectir have been filed in many LMICs and are expected to expire in 2038.

Bedaquiline is a crucial antibiotic for treating TB, particularly MDR-TB. It significantly improves treatment outcomes by reducing mortality and shortening therapy duration compared to older, less effective, often injectable, regimens. A long-acting formulation of bedaquiline could be useful as a new modality to increase adherence in the treatment of latent TB infection (LTBI, also known as TB preventive treatment, TPT), which is recommended by WHO for people living with HIV, household contacts of people with TB, and other risk groups. Bedaquiline long-acting is in phase I and data on safety and efficacy are still immature. Although the compound patent expired in 2023, Janssen owns several patents in LMICs on long-acting formulations of bedaquiline expiring between 2038 and 2041.

Delpazolid is an investigational antitubercular agent. It is being studied in combination with delamanid and bedaquiline. Delpazolid is a promising oxazolidinone antibiotic being developed for the treatment of TB. Currently in phase II clinical trials, delpazolid has demonstrated improved efficacy and safety compared to linezolid. The recently completed DECODE phase IIb trial evaluated different doses of delpazolid (up to 1200mg once daily) in combination with a backbone regimen of bedaquiline, delamanid, and moxifloxacin for the treatment of pulmonary TB. The study found that delpazolid was safe and well-tolerated, while promising signs of efficacy for drug-sensitive TB. However, the trial had limitations, including a small sample size that resulted in wide confidence intervals and the absence of a standard of care control arm for comparison. Despite these limitations, the trial results suggest delpazolid could be a strong candidate for treating drug-resistant TB. As the clinical data are still immature, the drug candidate remains in the watchlist. The primary patent on delpazolid is filed or granted in key countries of manufacture such as India, China and South Africa and is expected to expire in 2029. Secondary patents with an expected expiry date in 2031 are filed or granted in a few LMICs.

Patent & licence data in LMICs

Acronyms & abbreviations list

Ganfeborole (GSK3036656) is an investigational agent, demonstrating early bactericidal activity with a low, once-daily oral dose after 14 days of treatment in participants with drug-susceptible pulmonary tuberculosis . While ganfeborole is highly potent and effective at low doses, it may pose a risk of teratogenicity . It is in phase II and data are still immature and therefore the drug candidate remains in the watchlist. Patents on the compound have been filed or granted in several LMICs and are expected to expire between 2031-2036. Additional secondary patents may be filed.

Patent & licence data in LMICs

Acronyms & abbreviations list

Macozinone (PBTZ-169) is a tuberculosis drug candidate that has demonstrated high potency against drug-susceptible and drug-resistant TB in preclinical studies. Macozinone has additive effects with many TB therapeutic agents, both marketed and in development, and has synergic effects with bedaquiline and clofazimine in preclinical models . As macozinone is in phase II, data are still immature and the drug candidate remains in the watchlist. Primary patents on macozinone have been granted in key countries of manufacture such as India, China and South Africa and are expected to expire in 2031. Secondary patents may be filed.

Acronyms & abbreviations list

Sudapyridine (WX-081) is a new agent being studied for TB with a mechanism of action similar to bedaquiline, functioning as an ATP synthase inhibitor. It could be important for MDR-TB, which remains a major global health challenge. Sudapyridine has the potential to reduce some of the side effects observed with bedaquiline (such as cardiac issues with prolonged QT intervals, or liver toxicity and gastrointestinal issues). It is currently in phase III of development in patients with rifampicin-resistant pulmonary tuberculosis. Primary patents on sudapyridine are present in key countries of manufacture such as India, China and South Africa and are expected to expire in 2035. Secondary patents covering manufacturing processes and intermediates with an expected expiry date in 2037 are present in a few LMICs.

Acronyms & abbreviations list

Bemnifosbuvir is a nucleotide analog polymerase inhibitor designed to inhibit viral replication by impairing viral RNA polymerase. It has demonstrated potent pan-genotypic antiviral activity against HCV and has shown approximately 10-fold higher activity than sofosbuvir in vitro, while retaining efficacy against sofosbuvir-resistant strains. Bemnifosbuvir’s safety profile has been favorable, with a low risk of drug-drug interactions and no food effect reported. When combined with ruzasvir, an oral NS5A inhibitor, the two compounds have shown synergistic antiviral effects in vitro. The combination of bemnifosbuvir and ruzasvir has demonstrated a high sustained virologic response rate of 98% (208/213) at 12 weeks post-treatment (SVR12) after just eight weeks of treatment in a phase II study. This regimen offers potential advantages over existing treatments, including a short treatment duration (8 weeks), low risk of drug-drug interactions, and efficacy across HCV genotypes 1-4, positioning it as a promising new option for HCV therapy. Atea’s primary patents on bemnifosbuvir, expected to expire in 2036, have been granted in 35 LMICs and are pending in another 14 LMICs. Atea owns several secondary patents on salts and polymorphs that may provide exclusivity until 2038-2042, as well as combinations with ruzasvir until 2039-2042 in many LMICs.

Ruzasvir is an oral NS5A inhibitor that also exhibits potent pan-genotypic antiviral activity against HCV. When combined with bemnifosbuvir, the regimen showed a high sustained virologic response after a short treatment duration, with minimal drug interactions and broad efficacy across multiple HCV genotypes, making it a promising therapy option (see also above in the bemnifosbuvir section). Ruzasvir was first developed by MSD and exclusively licensed to Atea in 2021. Primary patents, expected to expire between 2031 and 2033, have been widely withdrawn and kept in force only in a few European countries. Atea filed two combination patents for bemnifosbuvir + ruzasvir. The second combination patent, expiring in 2042, is pending in 17 LMICs.

Bepirovirsen is an investigational antisense oligonucleotide (ASO) therapy being developed for chronic hepatitis B. It targets all HBV messenger RNAs through a triple-action mechanism: (1) by reducing HBV replication, (2) by suppressing hepatitis B surface antigen (HBsAg) levels, and (3) by stimulating the immune system to potentially achieve a functional cure.

​In the Phase IIb B-Clear trial, approximately 10% of participants achieved sustained HBsAg and HBV DNA loss after 24 weeks of treatment. Efficacy was observed in both nucleos(t)ide analogue (NA)-treated and untreated patients. The ongoing Phase III B-Well program aims to further evaluate bepirovirsen’s potential, focusing on patients with HBsAg ≤3,000 IU/mL. HBV cure occurs rarely with monotherapy, and combination therapies are being evaluated. Cure rates are significantly higher in persons with lower HBsAg levels. The FDA has recognized bepirovirsen with fast-track designation, highlighting its status as the only single agent in Phase III showing promise for finite-duration therapy for HBV, with the possibility of functional cure in some patients. This represents a potential breakthrough in chronic viral hepatitis B treatment.

​GSK in-licensed bepirovirsen from Ionis (formerly Isis) Pharmaceuticals in 2019. Ionis holds the primary patent on bepirovirsen, which has been filed in many low- and middle-income countries (LMICs) and is expected to expire in 2032.​

Baloxavir marboxil is an FDA-approved oral antiviral for both the treatment and prevention of influenza. An oral one-dose, one-time treatment for influenza, could serve, in addition to its use in seasonal influenza, as a valuable tool in pandemic preparedness in the event of an outbreak with a highly virulent influenza strain. Single oral administration, with no requirement for companion drugs, would support simplified treatment delivery. As a drug in a new class of antiviral treatment for influenza, it could provide an additional layer of protection. WHO has included baloxavir marboxil in its 2024 revised influenza guidelines. A conditional recommendation was made for administering baloxavir marboxil to asymptomatic individuals exposed to zoonotic influenza viruses, such as H5N1, that are associated with high mortality. Baloxavir marboxil has also the potential to reduce influenza transmission due to a rapid effect in decreasing viral shedding.

Primary patents on baloxavir marboxil have been filed or granted in several LMICs to Shionogi and they are expected to expire between 2030-2036. Secondary patents may provide exclusivity in few LMICs until 2039.

acronyms & abbreviations list

Nirsevimab is a monoclonal antibody with activity against Respiratory Syncytial Virus (RSV). Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses. One dose of nirsevimab administered to infants as a single intramuscular injection prior to, or during RSV season, may provide protection during the RSV season. Infants have the highest incidence of severe disease, peaking at 1–3 months of age.

acronyms & abbreviations list

Clesrovimab is an investigational mAb, which in phase III trials was shown to be very effective in preventing RSV-associated hospitalisations and LRTI when administered as a single dose to infants of all weights from birth to 1 year, and entering their first season of RSV.

Patents covering clesrovimab have been filed or granted in more than fifty LMICs and they are expected to expire in 2036. Secondary patents covering a formulation expected to expire 2039 were filed in few LMICs. Other secondary patents may be filed.

Acronyms & abbreviations list

The MicroCoat platform technology employs a fluid bed coating process to produce individually coated drug micropellets, that regulate the rate of drug release, enabling taste masking and extended release as relevant. The technology is investigated for an application to a malaria treatment for paediatric populations in LMICs through the support of a UnitaidExplore grant . MicroCoat AS/AQ combines into a fixed-dose combination of taste-masked anti-malarial drugs artesunate and amodiaquine, offering ease of administration and improved palatability for children compared to marketed products (especially for amodiaquine, which is very bitter and thereby challenging for use in children), while maintaining the same efficacy and safety. The formulation has been designed to be suitable for infants and young children for the treatment of uncomplicated P. falciparum malaria in LMICs, by ensuring not only palatability, but also easier swallowing and more flexible dosing than standard of care. The product is stable at accelerated and long-term conditions and is in early clinical development.

A targeted combination of dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) has shown significantly improved response rates, progression-free survival, and safety compared to traditional chemotherapy. Both drugs are FDA-approved for use in children, with age-appropriate formulations available , and each may also be used as monotherapy for other MAPK pathway-driven tumours. However, the use of these medicines requires BRAF mutation testing, which may limit access in LMICs. Of notice, these agents have a broader indication, such as for melanoma, and have a large use in adult diseases. The primary patents on dabrafenib and trametinib (owned by Novartis) expire in 2025 and 2029 respectively. Secondary patents on the combination extend to 2030, and additional formulation patents may last until 2033–2038. The primary dabrafenib patent is present in over 30 LMICs, with secondary patents on the combination in 25 LMICs. As part of the PADO–cancer process, the MPP was asked to explore licensing options for this combination.

The combination of the active substances elexacaftor, ivacaftor and tezacaftor is the first triple combination therapy available to treat patients with the most common cystic fibrosis mutation. It has been approved for patients 12 years and older with cystic fibrosis who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is estimated to represent 90% of the cystic fibrosis population.

acronyms & abbreviations list

These laboratory-made proteins emulate the immune system’s ability to counteract harmful pathogens, including HIV. Although still in the early stages of development, broadly-neutralising antibodies demonstrate significant potential for use as HIV post-natal prophylaxis (PNP), due to their favourable safety profile and the convenience they may offer through a single administration covering the peri-natal and breastfeeding period via intramuscular injection,,. Despite potential benefits, crucial clinical data on the efficacy of monoclonal antibodies for PNP remain lacking. Specifically, there is a notable gap in understanding whether a single monoclonal antibody could suffice for prevention. If multiple mAbs are necessary, the cost could become a significant concern, especially when compared to cheaper small molecules.

Beyond their use in postnatal prophylaxis, broadly neutralizing antibodies (bNAbs) are also being investigated for HIV cure strategies. The RIO study explored the use of two antibodies that can complementarily neutralize HIV through distinct mechanisms of action (3BNC117 and 10-1074, also known as teropavimab and zinlirvimab) in cis-gender men participants who accepted to stop their HIV-antiretroviral treatment, indicating that a one-time infusion of this antibodies combination could sustain viral suppression for over a year in some participants . While these findings remain preliminary, they highlight the broader therapeutic potential of bNAbs beyond postnatal prophylaxis.

Immune checkpoint inhibitors (ICIs) have revolutionised oncology, opening new possibilities for cancer treatment through immunotherapy. These monoclonal antibodies block proteins that would otherwise prevent the immune system from attacking cancer cells. The most well-known in this class are PD-1 and PD-L1 inhibitors. Their versatility has led to approval for a wide range of cancers, with a robust and promising pipeline of new ICIs. The WHO EML Committee has recognised their therapeutic value by including certain ICIs for the treatment of cutaneous melanoma, underscoring their effectiveness and potential for broader application.

Notably, ICIs have shown promise in addressing some of the most pressing global cancer challenges, including breast and cervical cancers—the most commonly diagnosed and deadliest cancers among women in LMICs. Among people living with HIV, many cancers occur more frequently due to infectious origins, such as Kaposi’s sarcoma (linked to human herpesvirus 8), non-Hodgkin lymphoma (linked to Epstein–Barr virus), and cervical cancer (linked to human papillomavirus, HPV) . People living with HIV who are on antiretroviral therapy and virally suppressed can live longer, managing HIV as a chronic condition, and face similar health issues as the general population. As a result, cancer has emerged as a leading cause of death in this population, posing new clinical challenges. Despite the paucity of safety and efficacy data of ICIs in the HIV population, emerging studies suggest that ICIs treatments do not interfere with HIV management, reinforcing the value of these therapies for this population.

However, ensuring broad access to ICIs remains a challenge. Recognising this, the WHO EML Committee has recommended further efforts to improve the affordability of ICIs, including consideration of voluntary licensing through MPP. In addition to voluntary licensing of intellectual property, MPP’s support for hands-on technology transfer could help accelerate development and lower the costs of quality-assured biosimilar versions of ICIs for use in LMICs. In line with this, MPP has strategically prioritised ICIs as a class, with pembrolizumab, approved for 18 types of cancer, including certain early-stage and advanced cancers, identified as a flagship product for this class.

acronyms & abbreviations list

Pembrolizumab is an immune checkpoint inhibitor, specifically an anti-programmed death receptor-1 (PD-1) therapy, that enhances the body’s immune response to detect and combat tumour cells. It is a humanised monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which can target both tumour and healthy cells. Pembrolizumab as a single agent reduces the risk of death in NSCLC patients by 40%, significantly extending survival by more than a year with fewer sides effects compared to traditional chemotherapy . First approved in 2014, pembrolizumab has since gained approval for 18 types of cancer, including lung cancer and certain early-stage and advanced cancers. MSD holds the exclusive patent rights on pembrolizumab until 2028 with patents filed or granted in at least 15 LMICs.

Patent & licence data in LMICs

Acronyms & abbreviations list

Immune checkpoint inhibitors (ICIs) have revolutionised oncology, opening new possibilities for cancer treatment through immunotherapy. These monoclonal antibodies block proteins that would otherwise prevent the immune system from attacking cancer cells. The most well-known in this class are PD-1 and PD-L1 inhibitors. Their versatility has led to approval for a wide range of cancers, with a robust and promising pipeline of new ICIs. The WHO EML Committee has recognised their therapeutic value by including certain ICIs for the treatment of cutaneous melanoma, underscoring their effectiveness and potential for broader application.

Notably, ICIs have shown promise in addressing some of the most pressing global cancer challenges, including breast and cervical cancers—the most commonly diagnosed and deadliest cancers among women in LMICs. Among people living with HIV, many cancers occur more frequently due to infectious origins, such as Kaposi’s sarcoma (linked to human herpesvirus 8), non-Hodgkin lymphoma (linked to Epstein–Barr virus), and cervical cancer (linked to human papillomavirus, HPV) . People living with HIV who are on antiretroviral therapy and virally suppressed can live longer, managing HIV as a chronic condition, and face similar health issues as the general population. As a result, cancer has emerged as a leading cause of death in this population, posing new clinical challenges. Despite the paucity of safety and efficacy data of ICIs in the HIV population, emerging studies suggest that ICIs treatments do not interfere with HIV management, reinforcing the value of these therapies for this population.

However, ensuring broad access to ICIs remains a challenge. Recognising this, the WHO EML Committee has recommended further efforts to improve the affordability of ICIs, including consideration of voluntary licensing through MPP. In addition to voluntary licensing of intellectual property, MPP’s support for hands-on technology transfer could help accelerate development and lower the costs of quality-assured biosimilar versions of ICIs for use in LMICs. In line with this, MPP has strategically prioritised ICIs as a class, with pembrolizumab, approved for 18 types of cancer, including certain early-stage and advanced cancers, identified as a flagship product for this class.

acronyms & abbreviations list

Pembrolizumab is an immune checkpoint inhibitor, specifically an anti-programmed death receptor-1 (PD-1) therapy, that enhances the body’s immune response to detect and combat tumour cells. It is a humanised monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which can target both tumour and healthy cells. Pembrolizumab as a single agent reduces the risk of death in NSCLC patients by 40%, significantly extending survival by more than a year with fewer sides effects compared to traditional chemotherapy . First approved in 2014, pembrolizumab has since gained approval for 18 types of cancer, including lung cancer and certain early-stage and advanced cancers. MSD holds the exclusive patent rights on pembrolizumab until 2028 with patents filed or granted in at least 15 LMICs.

Patent & licence data in LMICs

Acronyms & abbreviations list

Aumolertinib is a third-generation molecular targeted drug that acts as an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with antineoplastic activity. It inhibits mutant forms of EGFR, including the T790M mutation. Aumolertinib has demonstrated significant benefits over standard first- and second-generation treatments included in the WHO Essential Medicines List for NSCLC. It is currently under review for approval by the European Medicines Agency (EMA) .  Aumolertinib compound patent is expected to expire in 2035, and it has been granted in key countries of manufacture such as India, China and South Africa. Secondary patents may provide exclusivity in few LMICs until 2036-2039.

Patent & licence data in LMICs

Acronyms & abbreviations list

Osimertinib is a third-generation molecular targeted drug that acts as an EGFR TKI, designed to target both EGFR-sensitising and EGFR T790M resistance mutations. It has demonstrated clinical activity against central nervous system (CNS) metastases and is approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Osimertinib has shown significant benefits over standard first- and second-generation treatments included in the WHO EML for non-small cell lung cancer. The EML committee has called on MPP to explore licensing opportunities for osimertinib . The primary patent on osimertinib is expected to expire in 2032 and has been granted in more than 60 LMICs.

Patent & licence data in LMICs

Acronyms & abbreviations list

Adagrasib is an oral Kirsten Rat Sarcoma Virus (KRAS) inhibitor designed to potently and selectively target the KRAS G12C mutation. It received accelerated approval from the US FDA in 2022 for the treatment of NSCLC and has demonstrated durable clinical benefits, including improved progression-free survival . Notably, in 2024, the US FDA also granted accelerated approval for adagrasib in combination with immunotherapy for adults with KRAS G12C-mutated colorectal cancer, further reinforcing its potential across multiple tumour types. Adagrasib primary patents have been filed in many LMICs and are expected to expire in 2038.

Acronyms & abbreviations list

Lazertinib is an oral, potent, and irreversible EGFR TKI that is highly selective for activating (EGFRm) and T790M resistance mutations. In 2024, the US FDA approved the combination of lazertinib and immunotherapy for first-line treatment of NSCLC harbouring the mutation. Research on lazertinib monotherapy is ongoing, highlighting its potential as an alternative treatment option for lung cancer. The primary patent on lazertinib has been granted in many LMICs including India and is expected to expire in 2034. There are secondary patents that may provide further exclusivity until 2038-2041 in many LMICs.

Sotorasib is an oral Kirsten Rat Sarcoma Virus (KRAS inhibitor designed to potently and selectively target the KRAS G12C mutation. It received accelerated approval from the US FDA in 2021 for the treatment of NSCLC. Notably, in January 2025, the FDA granted accelerated approval for sotorasib in combination with immunotherapy for adults with KRAS G12C-mutated colorectal cancer, further reinforcing its potential across multiple tumour types. The primary patent on sotorasib has been granted in many LMICs and is expected to expire in 2038. Several secondary patents on crystalline forms and processes are expected to expire between 2039 and 2040.

Immune checkpoint inhibitors (ICIs) have revolutionised oncology, opening new possibilities for cancer treatment through immunotherapy. These monoclonal antibodies block proteins that would otherwise prevent the immune system from attacking cancer cells. The most well-known in this class are PD-1 and PD-L1 inhibitors. Their versatility has led to approval for a wide range of cancers, with a robust and promising pipeline of new ICIs. The WHO EML Committee has recognised their therapeutic value by including certain ICIs for the treatment of cutaneous melanoma, underscoring their effectiveness and potential for broader application.

Notably, ICIs have shown promise in addressing some of the most pressing global cancer challenges, including breast and cervical cancers—the most commonly diagnosed and deadliest cancers among women in LMICs. Among people living with HIV, many cancers occur more frequently due to infectious origins, such as Kaposi’s sarcoma (linked to human herpesvirus 8), non-Hodgkin lymphoma (linked to Epstein–Barr virus), and cervical cancer (linked to human papillomavirus, HPV) . People living with HIV who are on antiretroviral therapy and virally suppressed can live longer, managing HIV as a chronic condition, and face similar health issues as the general population. As a result, cancer has emerged as a leading cause of death in this population, posing new clinical challenges. Despite the paucity of safety and efficacy data of ICIs in the HIV population, emerging studies suggest that ICIs treatments do not interfere with HIV management, reinforcing the value of these therapies for this population.

However, ensuring broad access to ICIs remains a challenge. Recognising this, the WHO EML Committee has recommended further efforts to improve the affordability of ICIs, including consideration of voluntary licensing through MPP. In addition to voluntary licensing of intellectual property, MPP’s support for hands-on technology transfer could help accelerate development and lower the costs of quality-assured biosimilar versions of ICIs for use in LMICs. In line with this, MPP has strategically prioritised ICIs as a class, with pembrolizumab, approved for 18 types of cancer, including certain early-stage and advanced cancers, identified as a flagship product for this class.

acronyms & abbreviations list

Pembrolizumab is an immune checkpoint inhibitor, specifically an anti-programmed death receptor-1 (PD-1) therapy, that enhances the body’s immune response to detect and combat tumour cells. It is a humanised monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which can target both tumour and healthy cells. Pembrolizumab as a single agent reduces the risk of death in NSCLC patients by 40%, significantly extending survival by more than a year with fewer sides effects compared to traditional chemotherapy . First approved in 2014, pembrolizumab has since gained approval for 18 types of cancer, including lung cancer and certain early-stage and advanced cancers. MSD holds the exclusive patent rights on pembrolizumab until 2028 with patents filed or granted in at least 15 LMICs.

Patent & licence data in LMICs

Acronyms & abbreviations list

Abemaciclib is an oral cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitor, approved by the US FDA for treating HR+/HER2- advanced breast cancer . CDK 4/6 inhibitors are the preferred treatment option for HR+/HER2- advanced breast cancer. The EML expert committee recognised its potential for future inclusion and recommended that MPP explore licensing opportunities to support affordable access. Abemaciclib primary patents have been granted in more than 40 LMICs and are expected to expire in 2029 in most countries.

Patent & licence data in LMICs

Acronyms & abbreviations list

Ribociclib is an oral CDK 4/6 inhibitor, approved by the US FDA for treating HR+/HER2- advanced breast cancer . CDK 4/6 inhibitors are the preferred treatment option for HR+/HER2- advanced breast cancer. The EML expert committee recognised its potential for future inclusion and recommended that MPP explore licensing opportunities to support affordable access. Ribociclib and abemaciclib are similar alternative treatment options. Ribociclib primary patents have been filed or granted in many LMICs and are expected to expire between 2027 and 2029. Secondary patents may provide exclusivity until 2031-2036 in many LMICs.

Patent & licence data in LMICs

Acronyms & abbreviations list

Trastuzumab, a humanised IgG1 monoclonal antibody used to treat HER2-overexpressing metastatic breast cancer, has been developed (from infusion initially) into a subcutaneous formulation using recombinant human hyaluronidase to enhance delivery by temporarily breaking down hyaluronan, a barrier-forming substance in the tissues beneath the skin. Approved in 2019, the subcutaneous formulation follows a fixed-dose regimen, making it easier and quicker to administer than the original intravenous version. Trastuzumab primary patents expired in 2012. Secondary patents on the subcutaneous formulation have been filed and granted widely in LMICs and are expected to expire in 2030.

Zanubrutinib is a BTKi approved by the FDA in 2023 for the treatment of CLL. Recognizing the important emerging role of BTKi as a therapeutic class in the treatment of CLL, the EML Committee advised that it would consider an application for zanubrutinib as therapeutic alternative for inclusion and recommended that MPP explore licensing opportunities to support affordable access. The primary patent on zanubrutinib was granted in few LMICs, including India, where it is expected to expire in 2034. Secondary patents on crystalline forms are expected to expire in 2037.

Patent & licence data in LMICs

Acronyms & abbreviations list

Apalutamide is an oral second-generation androgen receptor antagonist approved by the US FDA in 2018 . For the treatment of non-metastatic castration-resistant and metastatic castration-sensitive prostate cancer, clinical guidelines recommend androgen receptor antagonists, such as apalutamide, in combination with androgen-deprivation therapy as the standard of care. With approval for both of these advanced prostate cancer types, apalutamide emerges as a key therapeutic option. Apalutamide primary patents are expected to expire in 2027. Secondary patents may provide exclusivity until 2033-2038 in many LMICs.

acronyms & abbreviations list

Darolutamide is an oral second-generation androgen receptor antagonist approved by the US FDA in 2019. For the treatment of non-metastatic castration-resistant and metastatic castration-sensitive prostate cancer, clinical guidelines recommend androgen receptor antagonists, such as darolutamide, in combination with androgen-deprivation therapy as the standard of care. Unlike other second-generation androgen receptor antagonists, darolutamide has a distinct structure, which may offer advantages in tolerability and efficacy. With approval for both of these advanced prostate cancer types, darolutamide stands out as a key therapeutic option. Darolutamide primary patent has been granted in many LMICs and is expected to expire in May 2030. The patent term has been extended in few LMICs until 2035. Secondary patents have not been identified in LMICs.

acronyms & abbreviations list

A targeted combination of dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) has shown significantly improved response rates, progression-free survival, and safety compared to traditional chemotherapy. Both drugs are FDA-approved for use in children, with age-appropriate formulations available , and each may also be used as monotherapy for other MAPK pathway-driven tumours. However, the use of these medicines requires BRAF mutation testing, which may limit access in LMICs. Of notice, these agents have a broader indication, such as for melanoma, and have a large use in adult diseases. The primary patents on dabrafenib and trametinib (owned by Novartis) expire in 2025 and 2029 respectively. Secondary patents on the combination extend to 2030, and additional formulation patents may last until 2033–2038. The primary dabrafenib patent is present in over 30 LMICs, with secondary patents on the combination in 25 LMICs. As part of the PADO–cancer process, the MPP was asked to explore licensing options for this combination.

The incretin hormones are gut hormones that amplify nutrient-induced insulin secretion in response to meal intake. Incretin peptides, principally Glucagon-like Peptide-1 (GLP-1) and Gastric inhibitory polypeptide (GIP), regulate islet hormone secretion, glucose concentrations, lipid metabolism, gut motility, appetite and body weight, and immune function, providing a scientific basis for utilizing incretin-based therapies in the treatment of type 2 diabetes¹. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are attractive options for the treatment of T2DM as they effectively reduce glycaemia and weight while posing a low risk of hypoglycaemia. Some GLP-1 RAs also have documented beneficial effects on the cardiovascular system, chronic kidney disease and non-alcoholic fatty liver disease.

_{1 Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013.}

There are various approved formulations of semaglutide, to be administered orally or subcutaneously.

Subcutaneous semaglutide
Subcutaneous semaglutide, a once-weekly peptide-based GLP-1 RA, is highly effective in achieving and maintaining glycaemic targets in people with T2DM. It also promotes weight loss in adults with overweight or obesity and reduces the risk of major adverse cardiovascular events in this population . Additionally, semaglutide has been shown to significantly reduce the risk of kidney disease progression in adults with T2DM and chronic kidney disease. A label extension for risk reduction of chronic kidney disease (CKD) related events has been filed based on these findings, with a regulatory decision expected in the first half of 2025. Additional regulatory submissions are anticipated in 2025, following successful phase III trials investigating semaglutide’s potential to reduce heart failure outcomes and improve metabolic dysfunction-associated steatohepatitis (MASH). To date, semaglutide remains the GLP-1 RA with the most advanced clinical profile. Primary patents on semaglutide expiring between 2024-2026 have been or granted in few LMICs. Patents on the sub-cutaneous formulation expired in 2024. Novo Nordisk owns many secondary patents that may extend exclusivity until 2040.

Oral semaglutide
Oral semaglutide, a once daily peptide-based GLP-1 RA, is highly effective in achieving and maintaining glycaemic targets while also promoting weight loss in people with T2DM. Clinical trials have demonstrated additional benefits, including a reduction in major adverse cardiovascular events (MACE) in those with T2DM and either cardiovascular disease or chronic kidney disease. A label extension was submitted to the FDA for the prevention of major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) and/or chronic kidney disease (CKD) at the end of 2024. A higher-dose formulation of oral semaglutide has also been shown to support weight management in adults with obesity or overweight. As a result, regulatory filing for an obesity indication may take place in 2025, which would make it the first oral GLP-1 therapy approved for this use. The oral formulation of semaglutide may make it appropriate for use in resource limited settings as it is heat stable. Primary patents on semaglutide expiring between 2024-2026 have been or granted in few LMICs. Secondary patents on semaglutide solid compositions with salcaprozate sodium, an important excipient of the finished product, have been filed in about seventeen LMICs, including major manufacturing countries such as India, South Africa, China and Brazil where they are expected to expire in 2031. Novo Nordisk owns many secondary patents that may extend exclusivity until 2040.

Acronyms & abbreviations list

Tirzepatide, a once weekly sub-cutaneous dual GLP-1 / GIP RA, is highly effective in achieving and maintaining glycaemic targets in people with T2DM and promoting weight loss in adults with obesity or overweight. It has also been approved for the reduction of the severity of sleep-apnea in adults with obesity . Successful clinical trials demonstrated benefits in adults with obesity and heart failure with preserved ejection fraction, with an application for approval submitted in 2024. Ongoing phase III and phase II clinical trials are investigating its efficacy in major adverse cardiovascular events (MACE) in people living with T2DM and CKD in people with obesity with or without T2DM. The primary patent on tirzepatide has been granted so far in at least 37 LMICs, including India, and pending in another 14 with an expected expiry in 2036. Secondary patents on the subcutaneous formulation have been filed and granted widely in LMICs and are  expected to expire in 2039.

Acronyms & abbreviations list

Retatrutide (LY3437943) is an investigational once-weekly subcutaneous GLP-1/GIP/glucagon agonist. It has shown significant improvements in glycaemic control for people with T2DM and substantial weight reduction in those with obesity. Its safety profile is consistent with other incretin mimetics, making it a promising therapy. The primary patent on retatrutide has been granted so far in at least 16 LMICs, including India, and pending in another 30 LMICs with an expected expiry in 2038.

Acronyms & abbreviations list

Orforglipron, an investigational once-daily oral non-peptide GLP-1 RA, is currently in two phase III clinical trial programmes for T2DM and obesity, with results expected in 2025. Its oral formulation and fully synthetic nature make it a promising therapy. The patents on orfoglipron compound are granted in 32 LMICs and pending another 18 LMICs and is expected to expire is 2037.

Acronyms & abbreviations list

MPP  is exploring ways to improve access to long-acting insulin analogues in LMICs, where the burden of diabetes poses a profound challenge, and appropriate treatment options remain limited and/or non accessible. Analogue formulations of insulin offer significant clinical advantages over traditional human insulins that are currently the most widely used insulins in LMICs. Their improved pharmacokinetic profiles support better glycaemic control, reduce the risk of hypoglycaemia and allow for more flexible dosing schedules    . The clinical advantages of insulin analogues over human insulin led to their inclusion in the WHO Model List of Essential Medicines in 2021, recognising their potential to improve diabetes management globally. Despite these benefits, the high cost of insulin analogues continues to limit their uptake in LMICs, where human insulins remain more affordable and widely used. MPP’s engagement in this space seeks to address affordability challenges and contribute to broader access to newer, more effective diabetes treatments in underserved settings, while also monitoring progress in next-generation insulin formulations that offer sustained, longer-acting coverage with the potential to further reduce hypoglycaemia risk and ease the injection burden for people living with diabetes. Given the diversity within the class of insulin analogues, a snapshot card was not produced, as it would not adequately capture the specificities of the different products. While patents have expired for most insulin analogues (administered more often than weekly), technology transfer – including to strengthen regional manufacturing – could support an MPP intervention within this area.

Acronyms & abbreviations list

The incretin hormones are gut hormones that amplify nutrient-induced insulin secretion in response to meal intake. Incretin peptides, principally Glucagon-like Peptide-1 (GLP-1) and Gastric inhibitory polypeptide (GIP), regulate islet hormone secretion, glucose concentrations, lipid metabolism, gut motility, appetite and body weight, and immune function, providing a scientific basis for utilizing incretin-based therapies in the treatment of type 2 diabetes¹. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are attractive options for the treatment of T2DM as they effectively reduce glycaemia and weight while posing a low risk of hypoglycaemia. Some GLP-1 RAs also have documented beneficial effects on the cardiovascular system, chronic kidney disease and non-alcoholic fatty liver disease.

_{1 Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013.}

There are various approved formulations of semaglutide, to be administered orally or subcutaneously.

Subcutaneous semaglutide
Subcutaneous semaglutide, a once-weekly peptide-based GLP-1 RA, is highly effective in achieving and maintaining glycaemic targets in people with T2DM. It also promotes weight loss in adults with overweight or obesity and reduces the risk of major adverse cardiovascular events in this population . Additionally, semaglutide has been shown to significantly reduce the risk of kidney disease progression in adults with T2DM and chronic kidney disease. A label extension for risk reduction of chronic kidney disease (CKD) related events has been filed based on these findings, with a regulatory decision expected in the first half of 2025. Additional regulatory submissions are anticipated in 2025, following successful phase III trials investigating semaglutide’s potential to reduce heart failure outcomes and improve metabolic dysfunction-associated steatohepatitis (MASH). To date, semaglutide remains the GLP-1 RA with the most advanced clinical profile. Primary patents on semaglutide expiring between 2024-2026 have been or granted in few LMICs. Patents on the sub-cutaneous formulation expired in 2024. Novo Nordisk owns many secondary patents that may extend exclusivity until 2040.

Oral semaglutide
Oral semaglutide, a once daily peptide-based GLP-1 RA, is highly effective in achieving and maintaining glycaemic targets while also promoting weight loss in people with T2DM. Clinical trials have demonstrated additional benefits, including a reduction in major adverse cardiovascular events (MACE) in those with T2DM and either cardiovascular disease or chronic kidney disease. A label extension was submitted to the FDA for the prevention of major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) and/or chronic kidney disease (CKD) at the end of 2024. A higher-dose formulation of oral semaglutide has also been shown to support weight management in adults with obesity or overweight. As a result, regulatory filing for an obesity indication may take place in 2025, which would make it the first oral GLP-1 therapy approved for this use. The oral formulation of semaglutide may make it appropriate for use in resource limited settings as it is heat stable. Primary patents on semaglutide expiring between 2024-2026 have been or granted in few LMICs. Secondary patents on semaglutide solid compositions with salcaprozate sodium, an important excipient of the finished product, have been filed in about seventeen LMICs, including major manufacturing countries such as India, South Africa, China and Brazil where they are expected to expire in 2031. Novo Nordisk owns many secondary patents that may extend exclusivity until 2040.

Acronyms & abbreviations list

Tirzepatide, a once weekly sub-cutaneous dual GLP-1 / GIP RA, is highly effective in achieving and maintaining glycaemic targets in people with T2DM and promoting weight loss in adults with obesity or overweight. It has also been approved for the reduction of the severity of sleep-apnea in adults with obesity . Successful clinical trials demonstrated benefits in adults with obesity and heart failure with preserved ejection fraction, with an application for approval submitted in 2024. Ongoing phase III and phase II clinical trials are investigating its efficacy in major adverse cardiovascular events (MACE) in people living with T2DM and CKD in people with obesity with or without T2DM. The primary patent on tirzepatide has been granted so far in at least 37 LMICs, including India, and pending in another 14 with an expected expiry in 2036. Secondary patents on the subcutaneous formulation have been filed and granted widely in LMICs and are  expected to expire in 2039.

Acronyms & abbreviations list

Retatrutide (LY3437943) is an investigational once-weekly subcutaneous GLP-1/GIP/glucagon agonist. It has shown significant improvements in glycaemic control for people with T2DM and substantial weight reduction in those with obesity. Its safety profile is consistent with other incretin mimetics, making it a promising therapy. The primary patent on retatrutide has been granted so far in at least 16 LMICs, including India, and pending in another 30 LMICs with an expected expiry in 2038.

Acronyms & abbreviations list

Fixed-dose combination medicines for CVD, also known as polypills, have been shown to simplify treatment, improve adherence, and help manage key risk factors. These pills combine cholesterol-lowering medicines, blood pressure drugs, and, when appropriate, aspirin, to significantly reduce illness and death caused by atherosclerotic CVD. Their use is suggested for both primary and secondary prevention of CVD. The need for effective and accessible CVD prevention is especially important for people living with HIV, who face a higher risk of developing heart disease but have limited tailored prevention options. A recent study found that those who took a medicine that lowers cholesterol had fewer major heart problems than those who received a placebo over about five years, underscoring the importance of expanding prevention strategies in this group. The proven benefits and cost-effectiveness of fixed-dose combination therapies support their broader use and led to their inclusion on the WHO Essential Medicines List in 2023.

Acronyms & abbreviations list