Mortality rate still high – but significantly reduced
The mortality rate of about 25% in the study after the treatment is still significantly higher than typically seen in high-income countries such as the United States, where HIV-associated cryptococcal meningitis is less common and associated with a mortality of roughly 10-15%, Dr. Lawrence noted.
The rate is nevertheless among the lowest mortality rates ever reported within a clinical trial conducted in resource-limited settings, he explained.
“These results are a step in the right direction and a significant improvement on the rates of 40% to 45% reported with two-week L-AmB-based regimens in African settings,” Dr. Lawrence underscored.
Higher cost — but potentially more cost-effective
With a higher cost than AmB deoxycholate, L-AmB’s utilization in resource-limited settings has been a challenge: A single vial of L-AmB ranges from $80 to $200, according to some reports, and while 14-day dosing requires as many as 42 vials of L-AmB, even a 7-day regimen still requires 21 vials.
In comparison, the single-dose L-AmB regimen only requires an average of 10 to 11 vials per patient, but the regimen’s higher safety could translate to far greater cost savings, Dr. Lawrence explained.
“While the AmBisome regimen is technically more expensive in terms of drugs, we expect it to be cost-effective or possibly cost-saving when taking into account that there is less toxicity, fewer blood tests, less transfusions, etc., and possibly shorter duration of hospital admission,” he said.
Cost, supply controversy: ‘Black fungus’-related demand
The drug’s cost — as well as supply issues — have meanwhile become even more of a problem as L-AmB has unexpectedly also become urgently needed in the treatment of mucormycosis in India and Nepal, where the otherwise rare fungal disease, commonly known as “black fungus,” has been increasingly affecting COVID-19 patients and survivors.
Gilead had previously announced in 2018 its intention to make L-AmB more widely available at a price of $16.25 per vial, but “implementation of this has been slow,” Dr. Lawrence said.
As a result, Gilead is facing heightened pressure to implement the lower prices – and also improve substantial supply issues, with Médecins Sans Frontières (Doctors Without Borders) and dozens of other global organizations issuing an open letter to Gilead and partner Viatris in June calling for immediate action to implement the lower price and improve supply of L-AmB.
In a company statement, Gilead responded, detailing its “commit[ment] to the non-profit pricing for the treatment of cryptococcal meningitis” and to efforts to improve the public health crisis in India.
For their part, Dr. Lawrence and his colleagues are working on producing more research on the issue.
“We hope that the conclusive results of the AMBITION trial will give a much needed push to implement this program,” he said.
“We are also currently completing the cost-effectiveness analysis of the study, which we hope will provide additional evidence to support widespread implementation of this regimen and highlight further the urgent need to broaden access to AmBisome and flucytosine,” he said.
The trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA) (TRIA2015-1092), and the Wellcome Trust / Medical Research Council (UK)/UKAID Joint Global Health Trials (MR/P006922/1. The AmBisome was donated by Gilead Sciences. Dr. Lawrence had no disclosures to report.