African genetic data could change how essential medicines are prescribed
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A Ñî¹óåú´«Ã½-led policy brief shows that more than 10% of essential medicines may require pharmacogenomic guidance.
This has implications for regulation, procurement, manufacturing and patient safety across Africa.
Pharmacogenomics is the study of how a person’s genetic makeup affects their body’s response to medications.
The dosage information for drugs used in HIV treatment, malaria, cancer care, pain management, and transplantation is largely based on data taken from European patients, failing to include vital information about how essential drugs work in diverse African populations.
This is a central finding of the Target Policy Profile Framework to Leverage African Genomic Heterogeneity (TALAGH) project, which released a culminating policy brief, Integrating Genomic Testing into African Drug Policies, that guides decision-makers in using Africa’s diverse genomic data to inform drug policy, regulation, and clinical care.
When standard doses don’t fit African patients
Efavirenz (EFV), an antiretroviral medication, for example, is affected by CYP2B6 variation (a natural, inherited difference in the CYP2B6 gene), which is common in Africa. This increases the risk of over-exposure and neuropsychiatric side effects.
Tamoxifen, used in breast cancer treatment, may be less effective in some patients with CYP2D6-related differences in drug metabolism.
Primaquine, used in malaria treatment, can cause haemolytic anaemia in people with G6PD deficiency (common in people in malaria-endemic areas).
And in kidney transplantation, there are concerns that dosing protocols developed largely from European populations may underdose some African-ancestry patients on transplant medicines, with potentially serious consequences for graft survival.
“TALAGH’s work asserts that pharmacogenomics is a medicines policy issue, with implications for regulation, procurement, manufacturing, clinical care and patient advocacy,” explains principal investigator, Distinguished Professor Collen Masimirembwa, senior scientist at the Sydney Brenner Institute for Molecular Bioscience ().
Masimirembwa says that genomics can be integrated into drug registration, product labelling, clinical guidelines, pharmacovigilance, healthcare training and data infrastructure across Africa.
“We now have enough evidence that genetic variation can affect how people respond to medicines. It must move from research papers into concrete decisions, and that regulators can authorise and clinicians can use.”
From research evidence to real policy change
It has been done before.
Masimirembwa’s research on HIV drug EFV showed that patients, including many in Zimbabwe, Uganda, South Africa, Tanzania and Botswana, had neuropsychiatric adverse effects on the standard 600mg/day dose.
These adverse drug reactions then led to a change in Botswana’s HIV management policy in favour of dolutegravir, while the WHO also recommended a dose reduction of EFV from 600 mg/day to 400 mg/day.
“If we prioritise pharmacogenomic-guided prescribing, then we identify which patients need a different dose, a different medicine, closer monitoring, or genetic testing before treatment. This could reduce adverse drug reactions, avoid treatment failure, prevent wasteful switching between medicines and support more rational procurement,” he says.
Despite this achievement, adverse drug reaction reporting remains extremely limited, with only 1% of reports in VigiBase (a WHO global database for reporting adverse drug reactions) coming from African countries. This is despite Africans having up to 50% of global adverse drug reactions associated with efavirenz.
In a positive move, The TALAGH project convened regulators from more than 10 African countries, alongside the South African Health Products Regulatory Authority (SAHPRA) and other stakeholders, to share pharmacogenomics data that many regulators had not previously seen. Currently regulators and health systems must often rely on imported guidelines, incomplete safety data and broad assumptions about patient response.
“There is a lot of opportunity for a more formal relationship with the African Medicines Agency, including the possibility of Ñî¹óåú´«Ã½ serving as a technical partner able to help translate African pharmacogenomic evidence into regulatory guidance,” notes Masimirembwa.
Manufacturers need to be part of the conversation, too. Local generic manufacturers, including those in South Africa, could play a critical role in producing formulations that align with African pharmacogenomic evidence and clinical needs.
Building an African pharmacogenomics system
The TALAGH policy brief makes several recommendations. It calls for pharmacogenomics-informed product labelling through expert working groups within medicines regulators; capacity strengthening through healthcare professional training and continuing education; research to close knowledge gaps on African-enriched and African-specific variants; secure data infrastructure for genomic data; and the establishment of a pan-African independent technical working group through the Consortium for Clinical Pharmacogenetics in Africa to guide regulators on priority implementation of actionable clinical guidelines.
“My dream is that our work becomes the beginning of something larger: a continental pharmacogenomics consortium that can carry African data all the way from the laboratory to the patient. Regulators, laboratory scientists, clinicians, pharmacists, Africa CDC-linked testing networks, patient advocates and social, ethical and legal experts would work together to decide which medicines need new guidance, which tests are practical, which formulations are needed, and how patients can be protected from avoidable harm,” says Masimirembwa.