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Prof Collen Masimirembwa

Africa is the continent with the most genetic diversity, but is gravely underrepresented in genomic research, with only 2 percent of global genomic data coming from people of African ancestry as of 2021.

As a result, disease risk prediction and drug development has predominantly used data from European populations, with varying applicability to health outcomes in Africans.

This lack of representation in genomic studies impacts how patients respond to different treatments, and can lead to poor treatment outcomes, further exacerbating existing health inequities within Africa.

According to the Holistic Drug Discovery and Development (H3D) Centre at the University of Cape Town in South Africa, only 3.5 percent of clinical trials take place in Africa.

This has resulted in certain cancer and HIV treatments, for example, performing differently in patients in Africa than they do in patients of European descent.

Inclusion of Africans in genomic studies has been slow, while scientific discoveries based on populations of European ancestry are yielding new ways to diagnose, prevent and treat diseases.

Tapping into Africa’s vast genomic research potential will require steady investment, capacity-building, and collaboration to build an ecosystem for developing precision medicine in and for Africa.

Why do we need precision medicine?

In the same year the human genome was first decoded in 2003, African scientists recognised the importance of this development for health, establishing the African Pharmacogenomics Consortium (APC) and the African Society of Human Genetics (AfSHG).

The AfSHG went on to lead the highly successful Human Heredity and Health in Africa (H3Africa) programme to increase genomic data on African populations, which is now associated with nearly 100 000 samples and over 500 whole genome sequences.

Moreover, APC member countries — Nigeria, Kenya, Tanzania, South Africa and Zimbabwe — under the leadership of the African Institute of Biomedical Science and Technology, created a biobank to support pharmacogenomics research which now contains over 20 000 samples from nine major ethnic groups and disease/treatment cohorts.

Studies from these sources have found that the African population has 25 percent more genetic diversity than other groups worldwide, with significant differences within the continent.

This is why a drug developed in Europe and tested on people of European ancestry may not be safe or effective for patients from other regions of the world.

To understand the effect of genetic variations on drugs, the African Institute of Biomedical Science and Technology (AiBST) has been studying various drug-gene interactions in the treatment of breast and colorectal cancers, HIV, TB and on pain control in sickle cell disease patients.

In the treatment of breast cancer, it has shown that over 30 percent of patients carry an African population-specific variant discovered to be associated with lower enzyme function such that carriers of this variant have sub therapeutic amounts of the active metabolite of the drug tamoxifen.

Because of this variation, it was found that tamoxifen is not as therapeutically effective in this population.

In another study of the anti-retroviral drug efavirenz, it was found that a genetic variant, with very high frequency in Africa, explains why the drug was causing 30-40 percent of patients in Africa to experience severe neuropsychiatric side effects, compared to only around 5-10 percent of patients in Europe.

Similar population-specific effects in drug response were observed in the use of warfarin, which prevents blood clots, and in the use of 5-Fluorouracil and irinotecan in the treatment of gastrointestinal tumours.

These pilot studies involving over 500 patients clearly demonstrate that the use of some medicines developed and optimised for safety and efficacy in European populations would benefit from a genomics-guided treatment strategy when used in African populations.

As an alternative to developing one-drug, one-gene tests, AiBST researchers partnered with a biotech company to craft a genetic test called GenoPharm.

This chip has approximately 120 genetic markers, which have been confirmed to predict treatment response to over 100 drugs.

The genetic status output links translational software to predicted patient functionality, which in turn guides treatment with respect to the choice of drug and appropriate dosage.

Results are shared with the doctor and patient through a genomics information management system (GIMS) and results are archived for future use each time the patient requires treatment covered by the genetic variants on the GenoPharm chip.

Through funding from the Calestous Juma Science Fellowship, AiBST is building an African-centric genetic research ecosystem for the development of precision medicine for patients in Africa.

Based on pilot results from the 500 patients, AiBST is now preparing to roll out a precision medicine programme across Africa, termed Implementation of Pharmacogenetic Testing for Effective Care and Treatment in Africa (iPROTECTA).

This will be conducted with 6 000 patients in Kenya, Nigeria, Zimbabwe and South Africa to test effectiveness for the treatment of tuberculosis, gastrointestinal tumours and sickle cell disease.

As part of this implementation, programme capacity for pharmacogenomics-guided precision medicine will be established at Obafemi Awolowo University in Nigeria and at Strathmore University in Kenya.

Understanding the unique variation in African genomes is crucial to address the disproportionate disease burden in Africa and contribute to global pharmaceutical advancements. The iPROTECTA programme will therefore contribute to the building of a robust ecosystem for precision medicine in Africa. To this end, iPROTECTA has already completed training of nine MSc students in Genomics and Precision Medicine from different African countries (Benin, Nigeria, Kenya and Zimbabwe).

Fast-tracking capacity building for product development in Africa

In addition to the specific contributions to genomics-guided precision medicine, AiBST has a broader mandate to build an ecosystem for continental capacity for product development to address Africa’s health challenges.

While an increasing number of researchers at African institutions have acquired a wealth of expertise in biomedical research, there still remains a lack of resources, funding and collaboration, as well as a lack of established pharmaceutical and biotechnology industries to convert discoveries into clinical solutions for African populations.

AiBST therefore partnered with Stanford University to organize a translational research boot camp and conference to bring together scientists from across African universities and research institutes for training and collaboration using the SPARK translational research model.

The March 2023 boot camp and conference was attended by 50 university researchers from 15 countries.

The outcome was the establishment of a network of translational scientists in Africa, called SPARK Africa. SPARK Africa has a vision to enable academics to develop & commercialise pharmaceutics, vaccines, diagnostics and other life science products, created by Africans, to address the continent’s unmet health needs.

SPARK Africa provides a framework for national governments, funders and pharmaceutical companies to play a vital role in advancing product development on the continent. Sustained funding, conducive policy environments and government commitments to product development will enable more African scientists to collaborate across regions and strengthen the biomedical research and development ecosystem on the continent.

Prof Collen Masimirembwa is the founding president and chief executive of the African Institute of Biomedical Science and Technology (AiBST), Zimbabwe, is generating a robust Research and Development (R&D) ecosystem with a focus on novel diagnostics, therapeutics and prevention strategies that will accelerate genomic and pharmaceutical medicine capabilities and transform the standard of care in Africa.