Lenacapavir is an MPP priority since 2022. Its new mechanism of action and its long-acting properties (up to 6 months dosing interval) will likely make it an important product in HIV prevention and/or treatment (in combination with other medicines). The clinical programs continue to indicate favourable efficacy and safety profiles. Furthermore, lenacapavir has been prioritised by WHO in both PADO-5 and CADO-4¹.

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

Long-acting cabotegravir for HIV PrEP was licensed to MPP in 2022.

Cabotegravir is the only approved integrase strand transfer inhibitor (INSTI) for long-acting HIV treatment, in combination with rilpivirine. Long-acting cabotegravir has the potential of becoming a key component for other future long-acting regimens for HIV treatment that could be introduced in LMICs. Injectable cabotegravir and rilpivirine for HIV treatment are not currently listed in WHO guidelines.

Rilpivirine is the only NNRTI approved, in combination with cabotegravir, as a long-acting regimen for HIV treatment. However, rilpivirine cold chain requirements could make it difficult for this drug to be implemented in LMICs. Additionally, it has been reported that rilpivirine could increase the risk for depressive disorders and hepatic adverse effects. Furthermore, rilpivirine resistance would largely exclude future use of the NNRTI class drugs. Finally, cabotegravir and rilpivirine are currently not listed in WHO HIV treatment guidelines.

Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). It is being investigated for HIV treatment in combination with islatravir as once daily oral treatment and it has the potential to be an alternative treatment for PLHIV. Additionally, some of its development program is focused on infants and children. However, the evidence of clinical benefits over the standard of care is unclear. 

GS-1720 is a novel integrase strand transfer inhibitor (INSTI) that has demonstrated potency and is suitable for once-weekly oral dosing, likely in combination with GS-4182.

GS-4182 is a lenacapavir prodrug with improved bioavailability and potential for weekly oral administration. It is likely to be used for the development of weekly oral regimens.

Islatravir is the first drug of a new class called nucleoside reverse transcriptase translocation inhibitors (NRTTIs). Its new mechanism of action and its long-acting properties have the potential to make it an important product in HIV treatment. After a period of pause in clinical development involving islatravir due to safety concerns, Merck has recently resumed some islatravir’s development programs while monitoring closely its safety. Furthermore, islatravir is one of the most promising drugs studied in combination with lenacapavir for oral weekly treatment and is investigated in co-formulation with other medicines and in several long-acting technology platforms. 

MK-8527 is a new nucleoside reverse transcriptase translocation inhibitor (NRTTI). Results on its antiviral activity were presented at CROI 2024. MK-8527 is designed for weekly oral administration.

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

Presented at CROI 2024, the new Cabotegravir Ultra Long Acting (ULA) formulation could be administered every four months. CAB-ULA has the potential for less frequent dosing.

Bulevirtide was recently conditionally approved by EMA and is today the only specific treatment for hepatitis delta. The treatment's duration and the necessity of a daily subcutaneous injection may present some challenges in LMICs. Additionally, its safety and efficacy are still under evaluation and therefore bulevirtide has been included in the watchlist.

Quabodepistat (OPC-167832) is a molecule with a new mechanism of action that has potent antituberculosis activity and a favourable safety profile. It is now studied as part of a new, promising, TB regimen under the Project to Accelerate New Treatments for Tuberculosis (PAN-TB) program, in combination with delamanid, bedaquiline, and sutezolid (DBOS) or in combination with pretomanid, bedaquiline and sutezolid (PBOS).

BTZ-043 is an investigational agent, active against all tested Mycobacterium tuberculosis strains, including clinical isolates from MDR and XDR patients. The clinical data on BTZ-043 are still immature and therefore the drug candidate remains on the watchlist.

Delpazolid is an investigational antitubercular agent. It is being studied in combination with delamanid and bedaquiline. As the clinical data are still immature, the drug candidate remains in the watchlist.

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. The clinical data on GSK3036656 are still immature and therefore the drug candidate remains in the watchlist.

Macozinone (PBTZ-169) is a tuberculosis drug candidate that has demonstrated high potency against drug-susceptible and drug resistant Mycobacterium tuberculosis in pre-clinical studies. Macozinone has additive effects with many tuberculosis therapeutic agents, both marketed and in development, and has synergic effects with bedaquiline and clofazimine in preclinical models. Clinical data on macozinone is still immature.

Sudapyridine (WX-081) is a bedaquiline analogue, displaying antimycobacterial activity and low toxicity. Clinical data on sudapyridine is still unmature and therefore the drug candidate is listed in the watchlist.

Baloxavir marboxil, 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 a novel and highly virulent influenza strain. As a drug in a new class of antiviral treatment for influenza, it could provide an additional layer of defense and an option against viruses resistant to existing antivirals.

Gepotidacin is an investigational first-in-class oral antibiotic for treatment of uncomplicated urinary tract infections and of Uncomplicated Urogenital Gonorrhea (UUG). Gepotidacin is active against most strains of target uropathogens, such as E.coli and Staphylococcus saprophyticus, including isolates resistant to current antibiotics. Furthermore, due to gepotidacin’s mechanism of action, blocking bacterial DNA replication by inhibiting two vital enzymes, mutations in both enzymes are needed to significantly affect susceptibility to gepotidacin. This gives hope that this drug will stay effective as resistance would be harder to develop.

Immune check-point inhibitors (ICIs) are monoclonal antibodies, used for immunotherapy in the oncology field. ICIs block proteins that stop the immune system from attacking the cancer cells. Most known class representatives are PD-1 inhibitors and PD-L1 inhibitors. ICIs have been approved to treat a variety of cancers and many ICIs are under development. The WHO Essential Medicines List (EML) committee recognised their importance as a therapeutic class. Some of them are listed on the EML for the treatment of skin melanoma. In several cases, the WHO EML Committee recommended to continue working on strategies to improve the affordability of these medicines and also suggested some for consideration for licensing by MPP. Moreover, MPP technology transfer support could support a successful implementation by reducing development time and costs of biosimilar versions for use in LMICs.​ MPP has prioritized ICIs as a class, and specific molecules, such as pembrolizumab, are listed here as examples of this effort.

The intravenous formulation of paclitaxel was added to the EML in 2011 and used in the treatment protocols for many cancers. Pending confirmation of its safety and efficacy, this new mode of oral administration, currently under development, could be particularly promising for LMIC settings, and therefore have been included in the watchlist.

Immune check-point inhibitors (ICIs) are monoclonal antibodies, used for immunotherapy in the oncology field. ICIs block proteins that stop the immune system from attacking the cancer cells. Most known class representatives are PD-1 inhibitors and PD-L1 inhibitors. ICIs have been approved to treat a variety of cancers and many ICIs are under development. The WHO Essential Medicines List (EML) committee recognised their importance as a therapeutic class. Some of them are listed on the EML for the treatment of skin melanoma. In several cases, the WHO EML Committee recommended to continue working on strategies to improve the affordability of these medicines and also suggested some for consideration for licensing by MPP. Moreover, MPP technology transfer support could support a successful implementation by reducing development time and costs of biosimilar versions for use in LMICs.​ MPP has prioritized ICIs as a class, and specific molecules, such as pembrolizumab, are listed here as examples of this effort.

One of the immune checkpoint inhibitors prioritised by MPP is pembrolizumab. Pembrolizumab as a single agent reduces the risk of death in non-small cell lung cancer patients by 40%, significantly extending survival by more than a year with fewer sides effects compared to traditional chemotherapy. ​ Pembrolizumab is also indicated against several other cancers.

Osimertinib is a 3rd generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) approved by the Food and Drug Association and the European Medicines Agency . It has demonstrated significant benefits compared to standard first-line treatments of 1st and 2nd generations in the WHO Essential Medicines List (EML) for the treatment of non-small cell lung cancer. The EML committee called on MPP to explore licensing opportunities for osimertinib.

Aumolertinib is a 3rd generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI), that has demonstrated significant benefits compared to standard first-line treatments of 1st and 2nd generations in the WHO Essential Medicines List for the treatment of non-small cell lung cancer. Aumolertinib is under review for approval by the European Medicines Agency (EMA).

Adagrasib is an oral Kirsten Rat Sarcoma Virus (KRAS) inhibitor that received approval by the Food and Drug Administration (FDA) for the treatment of non-small cell lung cancer (NSCLC) in 2022 and showcases durable clinical benefits in patients.

The intravenous formulation of paclitaxel was added to the EML in 2011 and used in the treatment protocols for many cancers. Pending confirmation of its safety and efficacy, this new mode of oral administration, currently under development, could be particularly promising for LMIC settings, and therefore have been included in the watchlist.

Lazertinib is an investigational 3rd generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI), presenting superiority over the 1st generation of EGFR TKI. Lazertinib has a strong potential as alternative option for lung cancer treatment.

Sotorasib is an oral Kirsten Rat Sarcoma Virus (KRAS) inhibitor, that received accelerated approval by the Food and Drug Administration (FDA) for the treatment of non-small cell lung cancer (NSCLC) in 2021. A recent study showed that sotorasib offered significant benefits compared to the standard intravenous treatment.

Immune check-point inhibitors (ICIs) are monoclonal antibodies, used for immunotherapy in the oncology field. ICIs block proteins that stop the immune system from attacking the cancer cells. Most known class representatives are PD-1 inhibitors and PD-L1 inhibitors. ICIs have been approved to treat a variety of cancers and many ICIs are under development. The WHO Essential Medicines List (EML) committee recognised their importance as a therapeutic class. Some of them are listed on the EML for the treatment of skin melanoma. In several cases, the WHO EML Committee recommended to continue working on strategies to improve the affordability of these medicines and also suggested some for consideration for licensing by MPP. Moreover, MPP technology transfer support could support a successful implementation by reducing development time and costs of biosimilar versions for use in LMICs.​ MPP has prioritized ICIs as a class, and specific molecules, such as pembrolizumab, are listed here as examples of this effort.

Ribociclib is an oral Cyclin-Dependent Kinase 4 and 6 (CDK 4/6) inhibitor, approved by the Food and Drug Administration for the treatment of HR+/HER2- advanced breast cancer. The Essential Medicines List expert committee recognised its potential for future inclusion and recommended to MPP to explore licensing opportunities.

Abemaciclib is an oral Cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitor, approved by the Food and Drug Administration for the treatment of HR+/HER2- advanced breast cancer, recommended as the preferred option in the treatment of advanced breast cancer. CDK 4/6 inhibitors are the recommended preferred option in the treatment of advanced breast cancer. The Essential Medicines List expert committee recognised its potential for future inclusion and recommended to MPP to explore licensing opportunities. Abemaciclib has a similar safety profile to ribociclib but with a different dosing regimen, making it an alternative of interest.

The intravenous formulation of paclitaxel was added to the EML in 2011 and used in the treatment protocols for many cancers. Pending confirmation of its safety and efficacy, this new mode of oral administration, currently under development, could be particularly promising for LMIC settings, and therefore have been included in the watchlist.

Trastuzumab subcutaneous is a monoclonal antibody approved by the FDA in 2019 for the treatment of HER2+ overexpressing breast cancer. It is the same monoclonal antibody as intravenous trastuzumab with the advantage of being easier and more rapid to administer.

Ibrutinib s a Bruton's Tyrosine Kinase Inhibitor (BTKi) approved by the Food and Drug Administration in 2013 and added to the complimentary list of the Essential Medicines List for the treatment of chronic lymphocytic leukaemia (CLL). Ibrutinib demonstrated major benefits compared to chemo-immunotherapy. The Essential Medicines List expert committee recommended to MPP to explore licensing opportunities.

Zanubrutinib is a Bruton’s Tyrosine Kinase Inhibitor (BTKi) approved by the Food and Drug Administration in 2023 for the treatment of chronic lymphocytic leukaemia (CLL). Recognizing the emerging important 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 to MPP to explore it for licensing.

Apalutamide is a 2^nd generation androgen receptor antagonist approved by the Food and Drug Association in 2018. As a class of drugs, 2^nd generation androgen receptor antagonists improve overall survival in prostate cancer patients. Apalutamide is a strong potential alternative candidate.

Darolutamide is a 2^nd generation androgen receptor antagonist approved by the Food and Drug Association in 2019. As a class of drugs, 2^nd androgen receptor antagonists improve overall survival in prostate cancer patients. Darolutamide is a strong potential alternative candidate.

The intravenous formulation of paclitaxel was added to the EML in 2011 and used in the treatment protocols for many cancers. Pending confirmation of its safety and efficacy, this new mode of oral administration, currently under development, could be particularly promising for LMIC settings, and therefore have been included in the watchlist.

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.}

Cardiovascular fixed-dose combinations of several drugs (commonly known as “polypills”) have been shown to rationalize treatment regimens, improve adherence and better control risk factors. Polypills for the prevention of cardiovascular disease are made up of cholesterol-lowering agents, one or more blood pressure-lowering agents and, if necessary, acetylsalicylic acid (aspirin). Their recent inclusion in the WHO Essential Medicines List should improve the accessibility and affordability of these essential medicines, which have the potential to save millions of lives every year.

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.}

Carbetocin was approved by the FDA in 1997 and its heat-stable formulation added to the core list of the EML in 2019 for the prevention of postpartum haemorrhage based on similar effects compared to oxytocin for efficacy and safety outcomes. Contrary to oxytocin, heat-stable carbetocin does not require cold chain transport or refrigerated storage thus offering advantages and reducing the risk of quality loss compared to oxytocin in LMICs. Heat-stable carbetocin is promising for low resource settings.

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.

Voxelotor is a haemoglobin oxygen-affinity modulator approved by the FDA in 2019 for the treatment of sickle cell disease. About 90% of the global sickle cell population lives in LMICs. Voxelotor has a different mode of action from that of conventional standard of care therapies, which makes it relevant as additional treatment or in case of intolerance.

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.