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. 

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. 

Bulevirtide was recently conditionally approved by EMA and it is today the only specific treatment for hepatitis delta. However, questions remain about the length of treatment and the formulation requiring a daily subcutaneous injection, which could hamper its use 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 being studied as part of a new TB regimen, in combination with delamanid and bedaquiline, under the Project to Accelerate New Treatments for Tuberculosis (PAN-TB) program. 

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. Additionally, it could be critical during the early phase of a possible influenza pandemic, when vaccines may not yet be available and could also be used alongside or as an alternative to vaccines to mitigate possible challenges with vaccines distribution and use.

Gepotidacin is an investigational first-in-class oral antibiotic for uncomplicated urinary tract infections. 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 at the generics front.​

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 side effects compared to traditional chemotherapy. ​

The intravenous formulation of paclitaxel has been added to the EML in 2011 and used since in the treatment protocols for many cancers. This new mode of administration, without new requirement for diagnostics, makes the indication promising for LMIC settings pending their approval by recognised SRA (Stringent Regulatory Authorities), 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 at the generics front.​

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 side effects compared to traditional chemotherapy. ​

Osimertinib is a 3rd generation EGFR TKI. It has demonstrated significant benefits compared to standard first-line treatments of 1st and 2nd generations in the EML for the treatment of NSCLC. Osimertinib is approved by the FDA and the EMA.

A 3rd generation EGFR TKI, aumolertinib has demonstrated significant benefits compared to standard first-line treatments of 1st and 2nd generations in the EML for the treatment of NSCLC. Aumolertinib is under review for approval by the EMA.

Adagrasib is an oral KRAS inhibitor that received approval by the 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 has been added to the EML in 2011 and used since in the treatment protocols for many cancers. This new mode of administration, without new requirement for diagnostics, makes the indication promising for LMIC settings pending their approval by recognised SRA (Stringent Regulatory Authorities), and therefore have been included in the watchlist.

Lazertinib is a 3rd generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), pending approval from a recognised stringent registration (SRA) authority, 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 KRAS inhibitor, that received accelerated approval by the FDA for the treatment of 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 at the generics front.​

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 side effects compared to traditional chemotherapy. ​

Ribociclib is an oral CDK4/6 inhibitor, approved by the FDA in 2017. CDK 4/6 inhibitors are the recommended preferred option in the treatment of advanced breast cancer. The EML expert committee recognised its potential for future inclusion and recommended to MPP to explore it for licensing.

Abemaciclib is an oral CDK4/6 inhibitor, approved by the FDA in 2021, 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 EML expert committee recognised its potential for future inclusion and recommended to MPP to explore it for licensing. 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 has been added to the EML in 2011 and used since in the treatment protocols for many cancers. This new mode of administration, without new requirement for diagnostics, makes the indication promising for LMIC settings pending their approval by recognised SRA (Stringent Regulatory Authorities), 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 and can be administered more easily and rapidly.

Ibrutinib is a Bruton's tyrosine kinase inhibitor (BTKi) approved by the FDA in 2013 and added to the complimentary list of the EML for the treatment of chronic lymphocytic leukaemia. Ibrutinib demonstrated major benefits compared to chemo-immunotherapy. The EML expert committee recommended to MPP to explore ibrutinib for licensing.

Zanubrutinib is a Bruton's tyrosine kinase inhibitor (BTKi) approved by the FDA 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 2nd generation androgen receptor antagonist approved by the FDA in 2018. As a class of drugs, 2nd generation androgen receptor antagonists improve overall survival in prostate cancer patients. Apalutamide is a strong potential alternative candidate.

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

The intravenous formulation of paclitaxel has been added to the EML in 2011 and used since in the treatment protocols for many cancers. This new mode of administration, without new requirement for diagnostics, makes the indication promising for LMIC settings pending their approval by recognised SRA (Stringent Regulatory Authorities), 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 GLP-1 and 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.

_{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 inclusion in the EML 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 GLP-1 and 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.

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

Carbetocin was approved by the FDA in 1997 and its heat-stable 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. 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 LMICs 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. Young infants have the highest incidence of severe disease, peaking at 1–3 months of age.