By Richard Jefferys, Basic Science, Vaccines, and Cure Project Director, TAG
The history of antiretroviral (ARV) drug development offers many examples of compounds that were originally discovered and investigated by publicly funded academic researchers, before being acquired and ushered to market by pharmaceutical companies. Among them is azidothymidine (AZT), the first approved ARV, which was synthesized in the 1960s and then shown to have activity against retroviruses in a preclinical mouse study in 1974. The drug was ultimately patented by Burroughs Wellcome, which notoriously attempted to charge an outrageous price when it was green-lit by the U.S. Food and Drug Administration (FDA) as an HIV therapy. It took a now-legendary ACT UP protest at the New York Stock Exchange to force the company to back down and cut the price by 20 percent.
In HIV cure research, the current prospects for FDA approval—and the pathway toward it—are far less clear than those of ARV candidates. For non-ARV-based biomedical prevention approaches, such as passive immunotherapy with broadly neutralizing antibodies (bNAbs) and vaccines, there is at least clarity regarding what efficacy would look like (a high level of protection against HIV acquisition), but as yet no candidate has shown a level of success sufficient to be considered for approval.
Despite these uncertainties, pharmaceutical and biotech companies have been acquiring rights to some experimental cure and prevention candidates. Examples include several bNAbs, which are being tested for both therapeutic and preventive potential. These types of license acquisitions should not be assumed to be a bad thing; there can be both upsides and downsides. Pharmaceutical and biotech companies are more likely to have the resources and expertise to facilitate large-scale manufacturing and clinical evaluation compared with academic researchers. But, as is seen in ARV drug development, companies can also be reluctant to make their proprietary compounds available for studies in which they would be combined with candidates owned by others.
In the event that a candidate achieves sufficient success to gain FDA approval, the price issue will also loom large. As exemplified by the AZT protests, advocates have long pointed out the injustice of excessive, access-limiting profiteering on treatments developed with public support.
For these reasons, it is worth keeping an eye on the ownership of candidates as they progress through the cure and biomedical prevention pipelines. Here are two recent examples:
- PGT121 is a bNAb identified by academic researchers supported by the International AIDS Vaccine Initiative (IAVI) in collaboration with the biotech company Theraclone Sciences. While IAVI’s focus is on prevention (and typically involves negotiating agreements designed to secure affordable access if a product is developed), an exclusive license to develop and commercialize PGT121 for therapeutic use—potentially along with other bNAbs discovered using the same technology— was granted to Gilead Sciences in an agreement with Theraclone in 2014. Based on encouraging results in macaques infected with simian immunodeficiency virus, Gilead plans to partner a PGT121 derivative dubbed GS-9722 with vesatolimod, a compound the company developed that modulates immunity by interacting with toll-like receptor 7.
- The bNAb N6 was isolated by researchers from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH). Commercial licensing of discoveries at NIH follows an established process involving their Office of Technology Transfer; in the case of N6, an announcement was made in the Federal Register in November 2017 explaining that a license to GlaxoSmithKline was being considered. The parties are now negotiating the agreement.