HIV first-in-class pipeline sees high levels of innovation that targets drug resistance and latency reversal

There are 87 first-in-class products that act on a range of 50 molecular targets, which can broadly be classified as host or viral factor

The human immunodeficiency virus (HIV) pipeline is robust, with 450 products in active development that display a high degree of novelty and diversity. Promisingly, there are 87 first-in-class products that act on a range of 50 molecular targets, which can broadly be classified as host or viral factors, indicating a high level of innovation in comparison with the marketed products, says GlobalData, a leading data and analytics company.

The company’s recent report, ‘HIV: First-in-Class Therapies Target Major Unmet Needs Including Drug Resistance and Latency Reversal’, reveals that the majority of the 10 highest-ranking targets have demonstrated evidence, either in vitro or in vivo, of latency-reversing potential and/or efficacy in drug-resistant HIV strains. This encouraging trend demonstrates that first-in-class innovation is centered on addressing these major unmet needs in the HIV market.

Sarah Elsayed, Pharma Analyst, GlobalData, commented, “The persistence of latent HIV reservoirs in antiretroviral therapy (ART)-treated patients represents a major barrier to the development of a functional cure, while the global rise in HIV drug resistance compromises the significant advances in disease management that have been achieved since the 1980s. However, the most pressing unmet need remains to be a cure that results in viral eradication.”

First-in-class targets were integrated into a proprietary matrix assessment that ranks them according to their therapeutic and commercial potential within HIV market. Interleukin 2 receptor subunit beta (IL2RB) was found to have the highest ranking. It has a role in stimulating the immune response by activating the potent IL-2 signaling pathway that results in suppression of viral replication eventually. Also, the drug candidate possesses latency-reversing potential as shown in the preclinical investigations. Other first-in-class targets with strong therapeutic potential include those targeting Toll-like receptor (TLR3) and Protein kinase C (PKC) family.

Furthermore, HIV vaccines have a strong presence in the overall pipeline (27.2 per cent). Preventive and curative vaccines have received high attention in research recently, since they may potentially translate into a cure that will eradicate the virus and help control the HIV pandemic. Despite the promising outlook, vaccines have historically suffered from high failure rates due to the particular nature of HIV and the low clinical trial participation rates globally.

Cell/gene-based therapy is also being investigated in the early stages of development, with two first-in-class products, both of which are at the discovery stage. It is different from the conventional antiretroviral treatment, since it can potentially be translated into a revolutionary cure in the near future.

Elsayed concludes, “Although 60 per cent of these pipeline drugs are still in early development, the innovation of molecular targets is promising and presents the potential to expand the existing HIV drug classes, which have not
completely fulfilled the primary unmet need for long-acting therapies.”