After the fall of the al-Assad regime in Syria, large stockpiles of the illicit drug captagon have reportedly been uncovered.
The stockpiles, found by Syrian rebels, are believed to be linked to al-Assad military headquarters, implicating the fallen regime in the drug’s manufacture and distribution.
But as we’ll see, captagon was once a pharmaceutical drug, similar to some of the legally available stimulants we still use today for conditions including attention-deficit hyperactivity disorder (ADHD).
Captagon was once a pharmaceutical
Captagon is the original brand name of an old synthetic pharmaceutical stimulant originally made in Germany in the 1960s. It was an alternative to amphetamine and methamphetamine, which were both used as medicines at the time.
Captagon has similar effects to amphetamines. It increases dopamine in the brain, leading to feelings of wellbeing, pleasure and euphoria. It also improves focus, concentration and stamina. But it has a lot of unwanted side effects, such as low-level psychosis.
The drug was originally sold mostly in the Middle East and parts of Europe. It was available over the counter (without a prescription) in Europe for a short time before it became prescription-only.
It was approved only briefly in the United States before becoming a controlled substance in the 1980s, but was still legal for the treatment of narcolepsy in many European countries until relatively recently.
The illegally manufactured version is usually referred to as captagon (with a small c). It is sometimes called “chemical courage” because it is thought to be used by soldiers in war-torn areas of the Middle East to help give them focus and energy.
For instance, it’s been reportedly found on the bodies of Hamas soldiers during the conflict with Israel.
Black-market captagon is now nearly exclusively manufactured in Syria and surrounding countries such as Lebanon. It’s mostly used in the Middle East, including recreationally in some Gulf states.
A recent report suggests captagon generated more than US$7.3 billion in Syria and Lebanon between 2020 and 2022 (about $2.4 billion a year).
What we know about illicit drugs generally is that any seizures or crackdowns on manufacturing or sale have a very limited impact on the drug market because another manufacturer or distributor pops up to meet demand.
So in all likelihood, given the size of the captagon market in the Middle East, these latest drug discoveries and seizures are likely to reduce manufacture only for a short time.
Though several South African companies are producing HIV and TB medicines, the active ingredients that go into these medicines are usually imported from India or China. Now, a local company is planning to break new ground by making the active ingredients for two important TB medicines in Pretoria. We zoom in on the company’s efforts and outline some of the obstacles to getting such local production off the ground.
South Africa has a relatively robust pharmaceutical sector. Approximately 60% of the medicines sold in South Africa are locally produced, according to Dr Senelisiwe Ntsele, writing in an opinion piece for the Department of Trade, Industry and Competition (dtic).
But most of the time we are not producing these medicines from scratch. In fact, like most countries in the world, we mostly import the ingredients that make the medicines work – commonly referred to as active pharmaceutical ingredients, or APIs. In addition to APIs, medicines contain other inactive substances that maintain their form and structure and assist in their delivery: such as binders, stabilisers, and disintegrants.
Around 98% of the APIs used in locally formulated medicines are imported and South Africa spends around R15 billion a year importing APIs, according to Ntsele.
Government has tried to address South Africa’s dependence on imported APIs as part of its broader strategy to bolster the local pharmaceutical industry, which is identified as a priority sector for investment in the country’s Industrial Policy Action Plan. Several government departments provide support to the local pharmaceutical sector, including for local establishment of API manufacturing capacity. These departments include the dtic, the Department of Science and Innovation (DSI), the Technology Innovation Agency (TIA), and the Industrial Development Corporation (IDC) – South Africa’s development finance instrument.
In a bid to reduce the country’s reliance on imported APIs, Ketlaphela – a state-owned API manufacturing company – was announced in 2012. The plan was that Ketlaphela would produce APIs used in HIV medicines, but after multiple setbacks the initiative never got off the ground. Spotlight reported on the history of Ketlaphela in more detail here.
Turning to the private sector
Less well known than Ketlaphela, are government’s efforts to support API manufacturing capacity in the private sector. One private company that has received such government support and seem set to start delivering is Pretoria-based Chemical Process Technologies Pharma (CPT Pharma) that was established in 2014.
CPT Pharma is a subsidiary of Chemical Process Technologies, a company with many years of experience in chemical manufacturing and synthesis, including manufacturing of APIs for animal medicines. Human medicines, CPT Pharma’s core business, have stricter production management and quality control standards than those for animal medicines.
Dr Hannes Malan, Managing Director of CPT Pharma, told Spotlight that the company has 14 APIs in its pipeline, with a strong focus on TB medicines.
CCPT Pharma is a subsidiary of Chemical Process Technologies. (Photo: Supplied)
In 2023, the company secured a license from USAID to produce API for rifapentine, a drug widely used for TB prevention, and in 2022 they secured a licence from the Medicines Patent Pool to produce API for molnupiravir, a treatment for COVID-19. Malan pointed out that these two licenses were agreed with organisations aiming to expand the presence of API manufacturers in Africa – unlike typical arrangements driven by pharmaceutical companies looking to secure their own supply chains.
“For all the other APIs that we’re working on [beyond molnupiravir and rifapentine], we’re either working on technical packs [technical information about the API] that were available in the public domain or technologies that we’ve developed ourselves,” said Malan.
“Our approach has always been to look at the molecules, look at the market value, look at the technology, and then see if there’s an opportunity for us to develop technology that allows us to produce these compounds cost competitively,” he said.
“We really believe that to be competitive and independent, you have to have your own technology. Doing a technology transfer from Big Pharma does not make you independent,” Malan added.
How to fund it all?
In 2017, the company completed a pilot plant for making APIs. Then in 2020 it received approval from the South African Health Products Regulatory Authority (SAHPRA) to produce APIs for human use. The plant was built for R50 million, funded jointly by the IDC, TIA, and CPT Pharma.
Malan said that that the IDC and TIA also supported trial runs to test CPT Pharma’s manufacturing processes and technology. These tests included several APIs in development, such as isoniazid, a drug commonly used to prevent and treat TB.
The company has also secured funding from several international donors. The Gates Foundation provided support to develop manufacturing technology for the anti-malarial drug amodiaquine, as well as tuberculosis medicines bedaquiline and pretomanid. GIZ, a German development agency involved in a European Union project to boost vaccine and health product production in Africa, supported the company’s work on molnupiravir and dolutegravir – a widely used HIV medicine. USAID and the DSI are supporting the company’s work on developing rifapentine API manufacturing capacity.
Most of this financial support has been in the form of grants.
Still building new plants
While CPT Pharma has secured local and international funding to help construct a pilot plant and to develop its API manufacturing technology and processes, Malan said more investment is needed to support the construction of two commercial-scale manufacturing facilities: an isoniazid API manufacturing plant and a multiple API manufacturing facility.
Construction of the isoniazid manufacturing plant has already commenced using existing land and infrastructure with support from the IDC, but it is short of around R20 million to complete it, said Malan.
Although the plant is not yet operational, he said a company has already expressed interest in buying CPT Pharma’s locally produced isoniazid API. This company, said Malan, is contracted to supply isoniazid to government. The plan is to initially supply the company with isoniazid API produced at its pilot plant
Malan said the commercial plant, when built, will be able to manufacture enough isoniazid API to supply around 60% of local demand.
Things are less far down the road with plans for a plant to produce multiple different APIs at commercial scale, and more work is needed to understand the financing requirements for this type of facility, said Malan. “We want to do a bankable study and a concept design for such a plant,” he said. Based on CPT Pharma’s own experience, published data, and the required complexity and capacity of the plant, Malan said it is estimated that construction for the multi-API plant will cost around US$100 million or R1.8 billion.
Plans to commercialise
Meanwhile, the company is moving forward with plans to commercialise isoniazid and rifapentine API from its pilot plant. Isoniazid and rifapentine is increasingly used together as TB preventive therapy.
“For rifapentine, our pilot plant is seen as the commercial plant,” said Malan. “At this stage, we can use the pilot facility and the pilot reactor to produce enough rifapentine to get into the market and to grow the market.” But in the long term he said the company hopes to transfer rifapentine manufacturing to a larger commercial plant.
The company is also planning to apply for World Health Organization (WHO) pre-qualification status for its rifapetine API. The goal is to conduct demonstration runs in the pilot plant by June 2025 and validate the WHO pre-qualification application in September 2025.
If achieved, WHO pre-qualification of CPT Pharma’s rifapetine API would show that the company’s APIs meet high-quality standards. It would also allow CPT Pharma to supply rifapentine API to companies producing medicines for the broader African market, for which a significant proportion of medicines are procured by donors requiring WHO PQ approval.
Note: The Gates Foundation is mentioned in this article. Spotlight receives funding from the Gates Foundation. Spotlight is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
The groundbreaking mRNA Technology Transfer Programme, launched in 2021, has achieved what was once unthinkable: from zero mRNA manufacturing capabilities in low- and middle-income countries (LMICs) in 2020, the initiative is positioned towards establishing 11 state-of-the-art good manufacturing practices (GMP) certified mRNA manufacturing facilities across 10 countries by 2030 and a further five facilities following later.
With all manufacturers in the Programme working on R&D across various diseases, this network is designed to meet the Global South’s R&D and mRNA vaccine needs. It stands ready to respond to any future pandemic to secure mRNA vaccine access across continents.
The transformative Programme, established by the World Health Organization (WHO) and the Medicines Patent Pool (MPP), works with the South African Consortium, Afrigen, Biovac, the South African Medical Research Council (SAMRC), and the Department of Science and Innovation and programme partners in Kenya, Brazil, Indonesia, India, Egypt, Nigeria, Ukraine, Bangladesh, Senegal, Tunisia, Serbia, Pakistan, Vietnam, and Argentina.
The Programme, support by South Africa, France, Belgium, Canada, the European Union, Germany, Norway, and the ELMA Foundation, has propelled LMICs to the forefront of pandemic preparedness. It represents an unprecedented global effort to ensure equitable health solutions, enabling LMICs to respond rapidly and independently to global health crises.
Charles Gore, Executive Director of the Medicines Patent Pool, stated, “From a standing start in 2020, the Programme’s growth has been nothing short of remarkable. After successfully developing a COVID-19 vaccine as proof of concept, the Programme is now expanding to address many other diseases relevant to LMICs. We are now poised to establish a sustainable mRNA vaccine production capacity that will benefit millions across the Global South, truly redefining what health equity can look like on a global scale.”
In a significant step forward, Sinergium Biotech is researching a human avian influenza (H5N1) mRNA vaccine candidate, and four R&D consortia have been formed in Southeast Asia, with more expected across other regions. The vaccines developed through this initiative will be shared across participating LMICs.
Unprecedented Capacity for Pandemic Preparedness and Resilience
With the manufacturing companies across four continents all based in LMICs, the Programme has fundamentally altered the mRNA vaccine production landscape. The initiative is projected to yield at least 60 million doses annually by 2030, with the potential to scale up to larger volumes that could supply up to two billion doses in the event of a declared pandemic. Leveraging future dose-reduction technologies, the Programme would have the capacity to cover all the mRNA vaccine requirements of the Global South.
As of December 2024, the mRNA Technology Transfer Programme has made significant progress, with nearly all site assessments completed. Half of the participating manufacturers have finalised their technology plans, with the remaining plans scheduled for completion by December 2025. Over a quarter of these manufacturers will have successfully received the technology platform transfer from Afrigen by the end of 2024, with the rest to be completed in 2025, marking an important milestone in the Programme. By December 2026, all manufacturing partners are expected to have demonstrated the technology at their respective sites, culminating in the full transfer of mRNA technology across all participants.
Prof. Petro Terblanche, CEO of Afrigen, highlighted, “The mRNA Programme has not only achieved our initial goals but exceeded them in every way. Afrigen’s work with our global partners has shown that LMICs can lead in R&D and manufacturing, transforming healthcare outcomes from diseases that affect the Global South. This Programme yet again demonstrates the power of partnerships and global collaborations.”
Dr Martin Friede, Coordinator at WHO, emphasised, “This mRNA Technology Transfer Programme exemplifies the power of collaboration in global health. We are delighted that WHO and the partners have signed an MOU with Prof Drew Weissman of the University of Pennsylvania to promote R&D of mRNA products for public health. We hope other institutions will also follow and share knowhow. We are committed to securing the necessary support to see these efforts through so that LMICs have the scientific and material resources to maintain this unprecedented level of pandemic preparedness.”
The Critical Role of Funding
Despite remarkable progress, additional funding is required to fully achieve the Programme’s ambition. An estimated US$200 million is needed to advance all manufacturers to GMP standards and continue to strengthen the R&D pipeline in support of at least 12 mRNA products currently in development. Encouragingly, Programme success has already attracted substantial catalytic co-investments. For example, for every dollar contributed by the Programme in the AFRO region, an estimated US$17 has been invested by regional stakeholders and other public health organisations.
Zwelethu (Zweli) Bashman, has been appointed chairman of the Pharmaceutical Industry Association (PTG), and Dr Stavros Nicolaou as deputy chairman. Four pharmaceutical associations, representing more than 80% of the industry, comprise the membership of the PTG.
Bashman is president of the Innovative Pharmaceutical Association South Africa (IPASA), and managing director of MSD South Africa and sub-Saharan Africa.
“Our goal is to contribute towards an environment that promotes growth and investment in the South African pharmaceutical industry while aspiring to broaden access to medicines for all people living in South Africa,” said Bashman.
Stavros Nicolaou has assumed the role of deputy chairman after serving as chairman of the PTG for several years.
Critical work done by South African scientists on mRNA vaccines for several diseases is at risk from patent claims from the pharmaceutical giant Moderna. Yet the government could easily protect this and other programmes by speeding up the passage of amendments to patent laws.
Every year, industry’s biggest players spend a combined US$4-billion on legal action. Even then, there was an audible gasp from the world’s media when Moderna, which developed a Covid vaccine with the US government, announced it was suing rivals Pfizer and BioNTech for “patent infringement”.
All three companies have made a fortune from selling Covid vaccines, and are now at war over the rights to the publicly-funded mRNA technology behind it.
After a year of suing and counter-suing in multiple jurisdictions, the European Patent Office stepped in two weeks ago and revoked one of Moderna’s patents covering “respiratory virus vaccines”. In doing so, the European Patent Office was seemingly defending BioNTech, a German company, from a ‘’threat’’.
This is not unusual. In most countries, governments can intervene to protect companies viewed as important to their national interest and can review, revoke, or withdraw patents. Most countries, but not South Africa.
Under Nelson Mandela, South Africa fought Big Pharma to secure affordable generic HIV medicines, and in the pandemic, the government made a valiant attempt to do the same for Covid vaccines by seeking a global waiver of intellectual property rules. But arcane apartheid-era laws still accept patent requests from companies – without substantive examination of the merits of the patent application and without the due process right to challenge it before it is granted. And, once a patent is granted, patient advocacy groups cannot easily revoke it.
There is legislation drafted which could give us the ability to challenge patents before they are granted, among other much needed mechanisms such as compulsory and government-use licensing.
In 2018, Cabinet approved a new Intellectual Property Framework which would give us this most basic right. It is compliant with international trade rules and should not be controversial. But, despite the fact the government has said it wants this legislation, has drafted it, and has even trained examiners on it, the law has sat languishing on the desk of the Minister of Trade, Industry and Competition Ebrahim Patel for several years. This has enabled Moderna to be granted far-reaching mRNA related patents in South Africa.
These patents put our widely-acclaimed mRNA vaccine manufacturing project, backed by the World Health Organisation (WHO) and others, at risk.
While the world quickly developed effective vaccines to combat Covid, intellectual property rules prevented us from making shots for ourselves. Western governments blocked our government’sefforts to suspend these global rules, leaving South Africa to wait at the back of the global queue, eventually paying unreasonably high prices for vaccines. Then at the height of our third wave of Covid infections, Johnson & Johnson exported vaccines which had been completed at a factory in the Eastern Cape to Europe, prioritising European customers over South Africa and the continent.
It was a dark time for South Africa. But amid the devastation, some hope came in the form of a small biotech company in Cape Town, Afrigen, when the WHO announced it would be at the centre of a new Global South programme to deliver vaccines.
Sharing technology
Moderna, Pfizer, and BioNTech have all refused to share their technology with the programme. But scientists from Afrigen and universities in South Africa as well as the South African Medical Research Council developed an mRNA vaccine of their own, using the publicly available information from the vaccine which Moderna developed with the US government. They have now begun sharing the technology with partners across the Global South – and are exploring vaccines for diseases such as TB too.
In a future pandemic, the programme could be used to rapidly share vaccine technology between low and middle-income countries, so that we don’t repeat the global inequality of the Covid vaccine rollout.
Except that Moderna filed far-reaching patents in South Africa which could be interpreted as covering any mRNA technology. And, under our faulty, unchanged intellectual property regulation system, the patents were granted.
Dozens of health and legal organisations have warned that the mRNA programme is vulnerable to patent claims from Moderna. While the company has givenassurances that it will not enforce patents on its Covid vaccine in some lower-income countries, including South Africa, the work of the programme on other diseases remains under threat.
The Medicines Patent Pool, which is implementing the project for the WHO, wants each programme partner (in the Global South) to resolve the issue of patents itself. But, by suing Pfizer and BioNTech, Moderna has signalled that it wants a total monopoly on mRNA technology. What, then, is Plan B if Moderna turns on the WHO-backed programme next?
When earlier this year, the Health Justice Initiative took legal action to force the Department of Health to disclose secret contracts with Covid-19 vaccine manufacturers, we won – and the documents revealed that vaccine procurement negotiations were one-sided, with pharmaceutical companies pressuring our government into unfair prices, terms and conditions.
Back to court
Now we are once again preparing to take the government to court to pass key provisions of the Patent Amendment Act. At the very least, we need proper patent examination, ways to oppose patents before and after they have been granted, and easy-to-use compulsory and government-use procedures in place. And we need this quickly.
We have seen how big pharmaceutical companies including Johnson & Johnson use our patent provisions to evergreen patents and then charge the state and sick patients more than they should by holding on to their patent monopolies.
We want to ensure that:
monopolies are not granted without examining their merits;
the public can exercise its right to oppose a patent before it is granted; and
the government can override patents and allow generic production where needed, as do the governments of many other countries.
After the stupendous effort for COVID vaccines and treatments, it may seem like other diseases were being neglected. Nevertheless, the US Food and Drug Administration suddenly had a fire lit underneath it, and got cracking with accelerated drug approvals. Now, 2023 seems to have brought plenty of new drugs to bolster the physician’s armamentarium – some are the first-ever treatment for their indications. Hopefully, with FDA and European Medicines Agency (EMA) approvals, South African approvals should not be too far behind.
Since the pandemic, hotly anticipated drugs have made a big splash or sunk without a trace. In 2021, semaglutide was approved for weight management, unleashing a wave of people using (and some abusing) the GLP-1 agonist for weight loss. Adagrasib, which targets KRAS, previously thought undruggable, was a major advance for the treatment of non-small-cell lung cancer and was one of a few notable new non-COVID pharmaceuticals.
Aducanumab/Aduhelm was the top tip for new drugs in 2021, but turned out to be an absolute debacle: it wound up being an astronomically expensive, mostly ineffective drug with significant side effects. There were even questions raised over how it got approved in the first place.
Alzheimer’s disease
Last year, Aduhelm seemed like yet another false start in the long battle against Alzheimer’s disease. This year though, it looks like help finally arrived for fight against the dreaded neurodegenerative disease with not one but two breakthrough drugs, both antiamyloid antibodies.
Up first is lecanemab/Leqembi from Eisai/Biogen. It targets the buildup of amyloid proteins in the brain, which otherwise lead to the formation of amyloid plaques and neurofibrillary tangles of tau protein, the hallmarks of the disease.
The other candidate is donanemab, which did not secure FDA approval last year, after pharma company Eli Lilly witnessed the disaster that was Aduhelm. It did show a reduction in decline in one measure of Alzheimer’s disease but not another, so its effects are a mixed bag.
Like Aduhelm, donanemab and lecanemab both have a serious downside: brain swelling, which claimed the lives of at three donanemab trial participants.
RSV
Previously minimised by the pandemic’s social distancing and routine masking, respiratory syncytial virus (RSV) experienced a resurgence in the wake of lifting these restrictions. RSV afflicts primarily those over 60 and young children. Among those 65 and older with RSV in the US, the Centers for Disease Control estimated 120 000 annual hospitalisations, with up to 10 000 of whom dying. Among children under 5, the figures are 58 000 annual hospitalisations and 100 to 300 deaths. Historically, RSV vaccine developments wound up being ineffective. Fortunately, this year saw the first approval for an RSV vaccine. A 120µg dose of their Arexvy vaccine produced statistically significant and clinically meaningful reductions in cases of lower respiratory tract disease caused by RSV in adults aged 60 years and older. Pfizer and Moderna are hot on HSK’s heels with their own vaccine applications.
Age-related macular degeneration
Apellis got an approval for pegcetacoplan this year, for geographic atrophy (GA) secondary to age-related macular degeneration, in its intravitreal injection. This is the first and so far only treatment for this indication. “The approval of SYFOVRE is the most important event in retinal ophthalmology in more than a decade,” said Eleonora Lad, MD, PhD, lead investigator for the phase 3 study. “Until now, there have been no approved therapies to offer people living with GA as their vision relentlessly declined. With SYFOVRE, we finally have a safe and effective GA treatment for this devastating disease, with increasing effects over time.”
Interestingly, Apellis also got an approval for paroxysmal nocturnal haemoglobinuria (PNH) with a patient-injectable version of pegcetacoplan. The disease results from the destruction of red blood cells by the immune system.
Lymphoma
Abbvie and Genmab’s epcoritamab, for certain cases of large B-cell lymphoma (LBCL), got accelerated FDA and EMA approval earlier this year. The FDA has also granted accelerated approval to Roche’s glofitamab. The drugs bind to binding to CD20 on malignant B cells and CD3 on T cells to kill cancer cells, creating an effect like CAR-T cell therapy but without the complexity (and presumably, cheaper too).
Major depressive disorder, postpartum depression
Mental health is full of gaps needing to be filled by effective treatments. Not much has made been added for depression since selective serotonin reuptake inhibitors (SSRIs) came onto the market in the 1990s. Zuranolone, from Biogen and Sage Therapeutics, is the first oral treatment for postpartum depression, which previously was treated only by IV injection in a healthcare facility. Unlike slow-acting SSRIs, this treatment, which targets the GABA-A receptor, is a short course.
Inflammatory bowel disease
There has been a steady drip of new biologic drugs for inflammatory diseases, such as bimekizumab (psoriasis and deucravacitinib which recently received FDA approval. Eli Lilly entered this crowded marketplace with ixekizumab. Now, after trouncing Novartis’ Cosentyx for psoriasis with its own mirikizumab, it pulled its application for that indication and switched it to ulcerative colitis – beating about a dozen competitors to be the first IL-23 inhibitor. It aims to get an approval for Crohn’s disease in 2025. Pfizer’s etrasimod for ulcerative colitis got approval in October 2023, and should receive EMA approval in 2024. Its phase 3 trial achieved 27% remission versus 7.4% for placebo.
Pulmonary arterial hypertension
Last is sotatercept, a new drug for pulmonary arterial hypertension (PAH), which previously had no real treatment. Unlike the current therapy aimed at simply dilating blood vessels, sotaracept targets BMPR-II signalling, addressing the cause of PAH. It earned a priority preview by the FDA based on its phase 3 trial data, with possible approval by March 2024.
Bada Pharasi, CEO of The Innovative Pharmaceutical Association of South Africa (IPASA)
Lessons from the COVID-19 pandemic have underlined the importance of continued investment into pharmaceutical innovation and R&D to not only bring life-saving medications to those in need, but to improve public health outcomes, writes Bada Pharasi, CEO of The Innovative Pharmaceutical Association of South Africa (IPASA).
From treatments for cancer, cardiovascular diseases and more recently, the COVID-19 vaccine, the pharmaceutical industry has made significant progress in the development of over 470 medications in the last 10 years alone.1
While the innovative pharmaceutical process typically takes between 10 and 15 years from discovery to regulatory approval2 – owing to factors including immense R&D costs, regulatory compliance, and the protection of patents3 – the fast-tracked development and approval of COVID-19 vaccines laid bare the need for pharmaceutical companies to be prepared to mitigate the risk of future outbreaks – and this means continued investment in innovation and R&D.
The pandemic underlined the need for countries to be prepared for outbreaks on the horizon. To ensure we can meet the next challenge, pharmaceutical innovations must match the pace at which diseases mutate. This kind of innovation is non-negotiable and requires continued investment as a safeguard against losing lives and endangering South Africa’s fragile healthcare system.
As we are in the midst of a cholera epidemic, as well as the recent measles outbreak,4 it’s important to continue driving innovation to treat diseases, with medicines developed by innovative pharmaceutical companies benefiting millions across the country every day.
This is evidenced by mortality rates for HIV/AIDS and TB in the country falling by 59.2% and 55.7% between 2007 and 2017, with at least 60 new medicines currently in the R&D pipeline to treat TB.5
While patents in pharmaceutical innovation protect the originators’ intellectual property, it is important that innovative medications be developed to ensure a continuous pipeline of access to generics once the patent has lost its exclusivity. This will drive consumer accessibility and affordability of life-saving treatments and medications that may otherwise be unattainable for many.
As we continue racing against the proverbial clock in protecting against current and future diseases, pharmaceutical companies should continue to invest in innovation and R&D to outsmart existing dreaded diseases, and provide agility and preparedness should the next unknown pandemic threaten. Our health, and lives, depend on it.
In recent times, new drug discoveries by independent large pharmaceutical companies have become increasingly rare, with almost 60% of new drugs discovered through mergers and acquisitions and drug licensing. Fortunately, an emerging trend of spinouts from academia and R&D investments heralds a promising shift in the industry’s interorganisational deal networks to improve research and development in the future. Researchers explore this new trend in Drug Discovery Today.
Launching a new drug in the market is risky, thanks to a low probability of success during the research and development (R&D) phase and the high costs involved. But through an improved understanding of disease biology, decision-making can be more streamlined through the effective use of scientific information.
With this in mind, researchers from Ritsumeikan University, Japan, led by Associate Professor Kota Kodama are uncovering how the trends in interorganisational deals in the pharmaceutical industry are changing to improve R&D productivity and drug discovery. “The network structure of innovation creation in the pharmaceutical industry has changed with the increasing emergence of start-up companies spinning out from academia and research institutions as players in the source of innovation,” explains Dr Kodama.
Their research suggests that the knowledge necessary for breakthrough innovation in drug discovery is more often than not obtained through alliance networks. Over the past decade, large research-based pharmaceutical companies have used research collaborations, innovation incubators, academic centres of excellence, public-private partnerships, mergers and acquisitions (M&As), drug licensing, and corporate venture capital funds as typical methods for external innovation. The researchers now aim to define the changes in the network structure and nature of such alliances that have occurred over the past decade to provide future strategic insights for industry and academic players involved in drug discovery.
Using data from the Cortellis Competitive Intelligence database, the researchers identified nearly 50 000 deals of various kinds related to pharmaceutical R&D across pharmaceutical, digital health software, animal drug, and medical device companies to uncover trends in the creation of new drugs for human use. They also studied the trends of 13 of the largest pharmaceutical companies with annual revenues of more than US$10 billion, who saw an improvement in their CAGR (compound annual growth rate) since 2015. The researchers noticed that the rising CAGR correlated to a significant change in M&A-related deals after 2015, indicating that M&A-related deals drive revenue growth for large pharmaceutical companies.
Furthermore, the number of organisations involved in interorganisational deals has been increasing yearly from 2012 to 2021. Although the number of organisations involved and the number of deals may be increasing, the density of the deal networks is decreasing annually, suggesting that networks are becoming more non-cohesive. The concentration of business relationships between organisations of certain areas in the network changed to dispersion around 2015, and new networks connecting different groups started to form after 2017. These trends are an important illustration of how the industry landscape is gradually evolving away from the traditional network in which large pharmaceutical companies drove drug discovery output. Now, interorganisational deals among more diverse players have become active and are driving R&D productivity for startups in biotechnology and pharmaceuticals.
A clear increase in the number of academia-owned spinouts of advanced technology and expansion of investment in start-ups is a positive sign. The emergence of new chemical modalities, such as biologics, oligonucleotides, and peptides that differ from traditional small molecule drug discovery indicate remarkable changes that have taken place over the past two decades. The trend of increased financing for start-up companies in personalised drug development is beneficial for patent creation and will positively impact innovation creation in the coming years.
“The presence of academia to support the technologies of these start-ups is becoming very important, and government and private support and investment in this area is boosting innovation. Our study shows that such medium- and long-term support may ultimately benefit the health and well-being of humankind,” concludes an optimistic Dr Kodama.
Research on fungi has helped transform tough-to-recycle plastic waste from the Pacific Ocean into key components for making pharmaceuticals, using a genetically altered version of an everyday soil fungus, Aspergillus nidulans. The researchers described their chemical-biological approach in Angewandte Chemie, a journal of the German Chemical Society.
“What we’ve done in this paper is to first digest polyethylenes using oxygen and some metal catalysts – things that are not particularly harmful or expensive – and this breaks the plastics into diacids,” said co-author Berl Oakley, professor at the University of Kansas.
Next, long chains of carbon atoms resulting from the decomposed plastics were fed to genetically modified Aspergillus fungi. The fungi, as designed, metabolised them into an array of pharmacologically active compounds, including commercially viable yields of asperbenzaldehyde, citreoviridin and mutilin.
Unlike previous approaches, Oakley said the fungi digested the plastic products quickly, like “fast food.”
“The thing that’s different about this approach is it’s two things – it’s chemical, and it’s fungal,” he said. “But it’s also relatively fast. With a lot of these attempts, the fungus can digest the material, but it takes months because the plastics are so hard to break down. But this breaks the plastics down fast. Within a week you can have the final product.”
The KU researcher added the new approach was “bizarrely” efficient.
“Of the mass of diacids that goes into the culture, 42% comes back as the final compound,” he said. “If our technique was a car, it would be doing 200 miles per hour, getting 60 miles per gallon, and would run on reclaimed cooking oil.”
Previously, Oakley has worked with corresponding author Clay Wang of the University of Southern California to produce about a hundred secondary metabolites of fungi for a variety of purposes.
“It turns out that fungi make a lot of chemical compounds, and they are useful to the fungus in that they inhibit the growth of other organisms – penicillin is the canonical example,” Oakley said. “These compounds aren’t required for the growth of the organism, but they help either protect it from, or compete with, other organisms.”
Oakley’s lab at KU has honed gene-targeting procedures to change the expression of genes in Aspergillus nidulans and other fungi, producing new compounds.
The researchers focused on developing secondary metabolites to digest polyethylene plastics because those plastics are so hard to recycle. For this project, they harvested polyethylenes from the Pacific Ocean that had collected in Catalina Harbor on Santa Catalina Island, California.
“There’ve been a lot of attempts to recycle plastic, and some of it is recycled,” Oakley said. “A lot of it is basically melted and spun into fabric and goes into various other plastic things. Polyethylenes are not recycled so much, even though they’re a major plastic.”
The KU investigator said the long-term goal of the research is to develop procedures to break down all plastics into products that can be used as food by fungi, eliminating the need to sort them during recycling.
“I think everybody knows that plastics are a problem,” Oakley said. “They’re accumulating in our environment. There’s a big area in the North Pacific where they tend to accumulate. But also you see plastic bags blowing around – they’re in the rivers and stuck in the trees. The squirrels around my house have even learned to line their nest with plastic bags. One thing that’s needed is to somehow get rid of the plastic economically, and if one can make something useful from it at a reasonable price, then that makes it more economically viable.”
Kagan Keklik, General Manager South Africa & Country Lead, Sanofi South Africa
Johannesburg, 30 August 22: Kagan Keklik has taken the reigns as General Manager South Africa & Country Lead of multinational pharmaceutical and healthcare company, Sanofi, in South Africa, at a time when revolutionary technology and medical interventions are set to change lives across Africa.
With all the business acumen needed, a passion for science and expertise across several therapeutic areas and products, Keklik is already inspiring excellence in the 500 plus workforce that he leads in South Africa.
Keklik has over 20 years of experience in the pharmaceutical sector where the positions he has held have spanned from managing products to leading teams in the Middle East, Eurasia, and South Asia. He has been with Sanofi for nearly 13 years, making him well-poised to take the company to new heights.
“Sanofi is dedicated to finding answers for patients by developing breakthrough medicines and vaccines. Our purpose is to chase the miracles of science to improve the lives of patients, partners, communities and our own people. We provide potentially life-changing treatments and life-saving vaccines to millions of people as well as affordable access to our medicines in some of the world’s poorest countries,” says Keklik.
Keklik is excited about the potential of the South African market. “South Africa is considered the gateway to the African continent and is an important market for the Sanofi Group. The people are driven and dynamic and there are great opportunities for growth. We are passionate about knowledge and technology transfer to ensure the local manufacturing of medicines. We sincerely look forward to helping to make a difference and I look forward to working with my team to drive change in the region,” says Keklik.
Keklik is a great proponent for forging important alliances, such as the strategic partnership with South African manufacturer, Biovac, for the local manufacture of vaccines through the transfer of manufacturing excellence, skills, and knowledge.
Keklik’s vision takes this even further: “As a world leader in the development and delivery of vaccines, we fully support continued investment in localised manufacturing and the sustainability of local vaccine supply. Through long-term partnerships such as the one we have with Biovac, we can ensure that South Africa can be a manufacturing hub that will improve the distribution of vaccines into neighboring countries.”
Supported by a strong team, Keklik is enthusiastic about unlocking not only the potential of the region but also of Sanofi itself. He sees himself as a transformative leader and believes in inspiring and empowering individuals and teams to achieve the company’s goals. At the same time, he is prepared to push limits to make a difference in both the prescription and over-the-counter medication markets.
“We are focused on growth and believe this can be achieved if we lead with innovation and accelerate efficiencies. I’ll be focusing on these levers over the next few years to ensure Sanofi maintains its position as a leading healthcare company, not only in South Africa, but throughout the region,” says Keklik.
