Nearly two decades ago, South African researcher Kelly Chibale recalls participating in a pioneering World Health Organization (WHO) meeting in Abuja, Nigeria, organized by TDR, the WHO-hosted Special Programme for Research and Training in Tropical Diseases, focusing on the concept of an African drug discovery network. 

For Chibale, the main outcome of that encounter was a bad case of food poisoning. But the researcher, who went on to found the University of Cape Town’s (UCT) Holistic Drug Discovery and Development Centre (H3D) a few years later, never forgot the idea.  

Twenty years later, in the wake of the COVID-19 pandemic fallout over the lack of research and development (R&D) and manufacturing on the continent, an African R&D network has finally come of age.

A network of African research institutions engaged in drug discovery research is taking full form. Earlier this year, some 21 research institutions spread across seven countries came together as the Grand Challenges African Drug Discovery Accelerator (GC-ADDA) co-sponsored by the Bill & Melinda Gates Foundation (BMGF) and LifeArc, a UK-based self-funded medical research charity.

The network was conceived in a 2017 conversation Chibale had with Peter Warner, BMGF Senior Program Officer, and Tim Wells, Chief Scientific Officer at Medicine for Malaria Venture (MMV), and the concept was championed by Warner within the foundation, Chibale recalls.

It was incubated between 2019 and 2023 against the backdrop of the COVID pandemic, with a series of Grand Challenges mini-grants disbursed to different African institutions that worked individually on key R&D challenges in malaria and TB drug discovery, among other issues.

Then, in January 2024, the GC-ADDA network came into its own with the $7.2 million grant from the BMGF and LifeArc.

Last month, LifeArc awarded another $6.3 million to H3D to establish a Center for Translational AMR Research (CTAR) at its UCT base.

The new CTAR project aims to identify and develop new precision antibiotics to combat several multidrug-resistant (MDR) Gram-negative bacteria, including Acinetobacter baumannii, which typically infects people with weakened immune systems, including in hospitals, and is a leading driver of antimicrobial resistance (AMR) on the continent.

Chibale, whose H3D Foundation will spearhead GC-ADDA, was in Geneva recently to discuss and promote the GC-ADDA network among African Ambassadors to the UN in Geneva Missions .

He sat down before that meeting to talk with Health Policy Watch about his vision and its development.

Flagship projects

“I can give credit to my colleague Solomon Nwaka of WHO/TDR for initiating the idea [of a network]. It was visionary. But the difference now is that this is a model that is based around specific, concrete innovation projects in research institutions on the continent,” said Chibale, whose H3D in Cape Town offers one such example.  

Based on lessons learnt in the two previous rounds of Grand Challenges Grants, the new GC-ADDA network will focus on four flagship projects. These will be led by research centers in Ghana, Cameroon, South Africa and Zimbabwe, but also involving the other African institutions, including those that were recipients of earlier grant rounds and will be integral parts of the developing network. 

“There was a closed call, to only those people who were already in the network and those strategically identified, to organize themselves, based on complementary expertise, and to propose a consortium project, which is on a much bigger scale than the individual projects,” Chibale said.

Out of seven applications received, two projects for R&D on new TB and malaria drugs were accepted. The malaria project, co-led by the University of Ghana and the University of Pretoria aims to deliver novel anti-malarial drug leads.

The TB project, led by researchers at South Africa’s Stellenbosch University with partners in Kenya and elsewhere, will take a new approach to TB by identifying new drugs that act by degrading essential proteins in Mycobacterium tuberculosis, the causative agent of TB. 

Complementary to that, two other novel projects have been funded as part of the $7.2 million grant from LifeArc and the Bill & Melinda Gates Foundation.

They include a project on African drug metabolism (DMPK) research, led by the Zimbabwe-based African Institute for Biomedical Science and Technology (AiBST)

Finally, there is an effort to build a library of African-derived natural products – so that the active pharmaceutical ingredients in traditional African medicines could be studied systematically.

R&D on drug metabolism in Africans

The drug metabolism project, headed by Collen Masimirembwa, who spent a decade in Sweden with AstraZeneca, has led to the creation of a dedicated laboratory, near Harare, to the all-important goal of studying how drugs are metabolized in livers obtained from African donors.

This, on a continent which boasts the greatest genetic diversity in the world.

“Why is this important for Africa? Is because the way Africans metabolize drugs is not well understood,” said Chibale, who co-authored an article last year in Nature Reviews Drug Discovery, describing the challenges.

The impact of Africa’s genetic variability on response to medicines is not well accounted for in African populations for two reasons, he explains: 

•  Only about 3.7% of clinical trials are conducted on the continent “and for obvious reasons, medicines are only optimized for people who take part”;
• Drug candidates are typically tested first in preclinical studies on cellular fractions containing drug metabolizing enzymes and liver cells from donated livers, the main organ in which food and drug chemicals are broken down in the body. In Africa, organ donation is uncommon.  

At the same time, genetic differences in the liver’s drug-metabolizing enzymes can mean that a drug may be processed more rapidly or slowly by the body. So, for instance, when the HIV drug Efavirenz was first introduced in Africa a while ago, a study in Zimbabwe found that the approved dose for Caucasians was toxic for some Africans who had a genetic mutation in the enzyme needed to process the drug, leading to a much slower metabolism.

“They observed people having adverse side reactions. Some would stop taking the medication, and some could even have died from the toxicity of the drug,” he relates. “Upon investigation, it turned out that people were actually being overdosed.”

“So this project aims to strengthen African drug metabolism research so that we can generate more data on how diverse populations in Africa break down drugs. And then we use that data to refine what we should be giving to people who carry particular genes, or genetic mutations in drug-metabolizing enzymes.”

Traditional drug library

Developing an African-based library of active ingredients derived from natural sources  another novel arm of the project, which will be led by the University of Buea in Cameroon.  

Like synthetics, medicinal plants also have active ingredients that bestow them with healing qualities, as part of natural (traditional or herbal) medicines, “these are molecules that come from plants, marine organisms or other natural sources,” he points out. 

“Africa has been endowed with a lot of these natural products. People use traditional medicines, right? But still, they have not been scientifically and clinically validated to the extent or point that they can receive approval from a stringent regulator.

“So the aim is to assemble a collection of well-characterized, purified natural products from Africa, and see how we can use them as a starting point for modern approaches to discovering a medicine – using them to test against causative agents of various diseases – communicable and non-communicable – whatever you want to do.

Concretely, this involves building a collection of such naturally derived “active ingredients”, which are already purified and characterized.

“They can be dispensed in what we call screening boxes – and made available to the African community to screen against any disease – in other words, providing starting points for drug discovery.”

Supporting local manufacturing of APIs

Complementary to the GC-ADDA R&D network is a parallel initiative in which H3D is engaged, which aims to support more local manufacturing of ‘active pharmaceutical ingredients’ (APIs) in Africa.

As was painfully evident during COVID, most of those APIs are currently produced in Asia and imported to Africa – and that hobbles the ability of African manufacturers to be competitive in the drug manufacturing space.

With the support of USAID, H3D, together with a private local pharma firm, Chemical Process Technologies (CPT) Pharma, is using and testing a “continuous flow reactor technology” that could make API production of antiretroviral drugs for HIV more economical, Chibale said.

“If and when we demonstrate the cost competitiveness of the process of making the three antiretroviral drugs we are working on as a pilot, we will license that technology to CPT Pharma, who can do the commercial manufacture.”

See related story: https://healthpolicy-watch.news/empowering-africas-pharmaceutical-future-the-critical-role-of-local-api-manufacturing/

Drumming up support for African R&D

The support of African governments, as well as the pharma industry, is critical to foster an ecosystem of R&D and manufacturing in Africa, says Chibale.

“And when I say support it is not always about giving money,” he stresses. “For African governments it can be as basic as supporting local researchers with the right policies that allow them, for example, to easily buy chemicals and reagents, which can be subject to high import fees or delays when donated equipment gets stuck in customs.”

In terms of the pharma industry, skills development and the exchange of scientists is a critical, practical pathway to fostering tech-transfer, said Chibale, whose own early formative experiences included a sabbatical as a visiting professor at Pfizer in 2008 at the company’s Sandwich R&D site in the United Kingdom.

Finally, he says H3D, as the GC ADDA network administrator through the H3D Foundation, can “bring excellence to this programme, because we’ve been through this ourselves.

“We can continue to provide access to infrastructure that we’ve developed, of course – with support from many partners, including pharmaceutical companies, including Medicines for Malaria Venture.

“And of course, the government of South Africa has been a major factor. It’s an important thing to highlight what a government can do, even when there are enormous social challenges.”

Image Credits: Je'nine May.