Effective treatments for COVID-19 could help prevent many deaths amid the slow rollout of vaccines in countries. But nine months since discovering that the inexpensive steroid dexamethasone helps reduce deaths among coronavirus patients on oxygen or ventilator support, the world has yet to find additional effective treatments for patients suffering from severe and critical coronavirus disease.
Sign up for Devex CheckUp
The must-read newsletter for exclusive global health news and insider insights.
There are hopes new antivirals and monoclonal antibodies currently in development will produce benefits, but experts are still waiting for the evidence.
But the fact that there are very few COVID-19 treatments available should serve as an incentive for the governments and the pharmaceutical industry to “double down” on research and development, Unitaid executive director Dr. Philippe Duneton told Devex in an interview.
“The fact that we have not [got] a drug that can kill the virus ... should be an incentive to do more,” he said.
“I think that there is a need ... not just to look [at] old drugs, but to double down [on] the effort in terms of screening of potential new drugs,” he added.
Clinical trials of other repurposed drugs, such as hydroxychloroquine and lopinavir/ritonavir, have shown no significant benefits for hospitalized COVID-19 patients. The World Health Organization has also not recommended the use of remdesivir for hospitalized patients based on data from its Solidarity Trials and other large-scale randomized trials that show no evidence the drug improves COVID-19 patients’ outcomes, including survival.
“People at the beginning thought that it was possible to repurpose drugs, so from hydroxychloroquine, to ivermectin, to colchicine, to remdesivir. A long list. But … I think that we can say that we don't see a real opportunity with old drugs … except dexamethasone,” Duneton said.
Unitaid, however, is including drugs such as ivermectin in its funded trials to fill in the gap in evidence.
“We need to finish the job, because I think that we have seen that people, for whatever good reason, I suspect, want to use drugs without evidence [of benefits]. That’s the situation. And I think it’s quite important to find out,” he said.
Ivermectin’s story shares similarities with hydroxychloroquine. Both drugs are cheap, widely available, and have been used to treat other diseases prior to COVID-19. But if it will have the same fate is yet to be determined.
He’s hoping for better outcomes for new antivirals in development, such molnupiravir, which is being developed by Ridgeback Biotherapeutics and Merck & Co. and is advancing to Phase 3 trials for outpatient use, along with early-stage antivirals being developed by Pfizer. He also hopes the second generation of mAbs, short for monoclonal antibodies, would be efficacious against the new COVID-19 variants and would be easier to administer.
In October 2020, the Bill & Melinda Gates Foundation entered into an agreement with Eli Lilly to develop the pharmaceutical company’s monoclonal antibody to treat COVID-19 in low- and middle-income countries. The agreement is part of the COVID-19 Therapeutics Accelerator, which works with but is separate from the ACT Accelerator, of which Unitaid is part.
The agreement reserved manufacturing capacity for the development of the therapy at the FUJIFILM Diosynth Biotechnologies facility in Denmark. But the partners decided not to push through with procuring Eli Lilly’s first-generation monoclonal antibodies after the emergence of concerning COVID-19 variants.
“The efficacy of the first-generation of mAbs were challenged by the variants in South Africa and in Brazil. And so ... there was no point to push this difficult production, and not-that-easy-to-use drugs, when we saw that, in fact, the clinical benefit was quite limited,” Duneton said.
But the Unitaid chief also explained that finding an effective treatment is just half the battle. The organization and its ACT Accelerator partners also need to ensure there is enough supply, and countries are accessing those supplies.
“The fact that we have not [got] a drug that can kill the virus ... should be an incentive to do more.”— Dr. Philippe Duneton, executive director, Unitaid
It’s a key lesson they have come to realize in trying to bring dexamethasone, oxygen therapy, and rapid antigen tests to countries over the past year.
Unitaid typically provides funding for late-stage R&D of new drugs and diagnostics for infectious diseases such as HIV and AIDS, and brings more affordable formulations to LMICs. During the pandemic, they’ve purchased dexamethasone and entered into volume guarantees for rapid antigen tests to reach LMICs.
But those efforts have not been fully maximized. There’s been limited uptake of rapid antigen tests that countries can get from the Global Fund to Fight AIDS, Tuberculosis and Malaria. In addition, a COVID-19 Oxygen Emergency Taskforce was set up in February to advocate for and coordinate an increased supply of oxygen in LMICs.
As countries experience new waves of infection, partners need to make an effort to let countries know dexamethasone is still available, Duneton added.
Preparing to address access challenges
While waiting for clinical evidence of new therapies, Duneton explained that Unitaid and its partners are working in parallel to ensure access for LMICs when and if new treatments prove to have a significant benefit for COVID-19 patients. They’re thinking about how to produce the treatments at scale, and how to ensure they are of quality and affordable for LMICs, he said.
Monoclonal antibodies, for example, are largely unavailable in lower-income settings, and when they are, they are only accessible to those who can pay.
“The kind of invisible work that we have been doing at the partnership is to look at the pipeline and to see, okay, if [a treatment] works, what is the situation?” Duneton said.
While there are challenges in supply, health and aid officials argue it’s not the only barrier to access.
The goal is also to reduce the time of uptake of new COVID-19 treatments between higher-income countries and lower-income countries, which has traditionally been the case for treatments for other diseases, such as HIV. He anticipates it won’t be easy, having seen huge demand and competition that arose with vaccines and other products during the COVID-19 pandemic.
But the push to build production capacity even before a treatment has proven efficacy can have its complications, too — as seen with remdesivir, which did not receive recommendation from WHO for use in hospitalized COVID-19 patients.
“There [were] a lot of generic companies [that] were ready to produce remdesivir. But it turns out, it was not a good thing to do,” Duneton said.
“So what kind of incentive, how we can push [for access in LMICs?] Can we organize volume guarantees [the way] we did, for example, for the rapid tests with the Gates Foundation, or incentivize generic manufacturers so we can have access for LMICs in all continents? It’s a lot of money, but that’s the kind of tool that we need to consider,” he said.
All these will require investments, and at the moment, the therapeutics pillar of ACT-A for which Unitaid is a co-convenor with Wellcome has a funding gap of over $3 billion. While they have received support from donors such as Norway, Germany, and the United States, Duneton said they need more.
Without additional funding, he said, it would be challenging for them to engage with manufacturers on volume guarantees for the products they plan to purchase, or reduce the time it takes to produce a proven treatment.
Update 4/22/21: This story has been updated with the names of the companies making molnupiravir.