Combating HIV through innovative medicine
Prof Sheng Qi’s research underpinned the regulatory approval of a life-saving medicine used by tens of thousands of people living with HIV.
Approximately 38 million people live with HIV around the world. Though 24.5 million people are accessing life-saving antiretroviral therapy, tragically hundreds of thousands of people still die from an AIDS-related illness each year in part due to the varied efficacy of antiretroviral drugs.
The Joint United Nations Programme on HIV/AIDS (UNAIDS) is leading the global effort to end AIDS by 2030 and access to effective antiretroviral therapy is vital if it’s to achieve this goal. Between 1996 and 2016, worldwide resistance to life-saving antiretrovirals ranged from 12% to 22% but research undertaken in the School of Pharmacy at UEA, and lead by Prof Sheng Qi, has supported global efforts to deliver more effective treatments, and save lives.
UEA scientists used their expertise to reveal the physical state of the drug in etravirine tablets and the underpinning mechanism of tablet stability. Their work led to the regulatory approval of etravirine which has now prescribed to tens of thousands of patients each year.
Supporting the regulatory approval of etravirine
The drug etravirine – marketed as Intelence™ – was developed by Janssen (part of a multinational pharmaceutical company Johnson & Johnson) for patients with drug resistant HIV.
To ensure the good absorption of the drug when delivered by oral tablets, Janssen had developed a special solid dispersion formulation technology. When it came to obtaining regulatory approval from the US Food and Drug Administration (FDA), the company had to prove that that these uniquely formulated tablets were stable and safe to use.
This is where UEA came in. Work undertaken by Prof Qi proved that etravirine was stably incorporated in the cellulose-based carrier, supporting Janssen’s in-house stability assessment. Prof Qi’s data was part of the package submitted for FDA regulatory approval by Janssen and, in 2008, etravirine became the first new NNRTI (non-nucleoside reverse transcriptase inhibitors prevent HIV it from duplicating) to be approved in over a decade in the US and Europe.
The cornerstone of HIV therapy
The positive health impacts of this regulatory approval have been huge and NNRTIs like etravirine are now the cornerstone of HIV therapy.
The World Health Organisation’s (WHO) first-line HIV therapy for middle income countries is a cocktail of three anti-HIV drugs from two different classes, including NNRTIs such as etravirine. Should first and second-line therapy be unsatisfactory, the WHO recommends third-line therapy with a minimal risk of cross-resistance to other HIV medicines. Three drugs are specifically recommended for third-line therapy, among which etravirine is the only reverse transcriptase inhibitor.
It is literally a life-saving medicine for patients in which the virus has acquired resistance to other anti-HIV drugs – and the therapeutic and clinical impact of etravirine is not limited to its use as a mono-therapy drug. The clinical efficacies and cost-effectiveness when being used as a part of combination therapy with other anti-HIV agents have been evaluated and recognised by various clinical trials around the world.
Etravirine is now approved for use in over 100 countries and has received additional regulatory approvals for use in children as young as two years old. Global sales of etravirine in the period 2014-2019 totalled EUR1.7 billion, a figure that does not include the provision of the drug at cost price through Janssen’s Global Access Partnership Program (GAPP) in middle- and low-income countries.
Janssen has also made the product available at low cost to middle and low-income countries and continues to donate the drug to HIV/AIDS charities.
The UEA team’s collaboration with Janssen generated three scientific publications which contribute to the understanding of solid dispersion technology and are highly cited by the wider pharmaceutical community who use the knowledge in product development of solid dispersions.
Today there are more than 25 types of pharmaceutical oral products that are formulated using solid dispersions technology.