Hyaluronic acid (HA) is becoming an increasingly popular drug delivery method due to its multiple functional groups, injectable applications, and sustained release formulations. Pradeep Dhal, Senior R&D Director at Sanofi, kicked off his presentation by outlining the structure of HA and highlighting its biocompatible and biodegradable nature.
The HA market value is approximately $ 15 billion. HA is widely used in cosmetics and medical products, such as Synvisc, for the treatment of osteoarthritis pain. HA treats osteoarthritis by rebalancing the viscoelastic properties of synovial fluid in knee joints.
The key technical advantage of HA is the fact that it can enable drug conjugation through various linkers, allowing for controlled, sustained drug release without burst effects. Dhal also stressed that the design of the linker and polymer degradation rate are critical for achieving the desired therapeutic profiles. He briefly presented data from animal models that showed that when Bupivacaine and methotrexate were conjugated to HA, the efficacy was extended.
GLP-1 and SGLT-2 are the major players in the anti-diabetes therapy landscape, and both Eli Lilly and Novo Nordisk have successful drugs in this space. Yet challenges remain, including the short half-life of peptides and sustained release without immunogenicity. So, Dhal discussed a Sanofi program that uses HA-based conjugates for once-weekly delivery of GLP-1 agonists for diabetes and obesity.
The experimental results showed that the HA-conjugated GLP-1 showed linear release over 10 -11 days. Furthermore, the animal studies demonstrated consistent glucose-lowering and weight loss effects with once-weekly dosing. However, Sanofi discontinued the programme due to commercial and strategic shifts away from diabetes.
In collaboration with Ascendis Pharma, Sanofi developed a technology called TransCon, which relies on a pH-sensitive linker to facilitate zero-order drug release, with the drug released in pure form and the polymer safely cleared.
In summary, HA is a highly versatile and promising platform for drug delivery due to its natural biocompatibility, biodegradability, and modifiable chemical structure. Its ability to form stable, injectable formulations and conjugate with various therapeutic agents enables sustained and targeted drug release. Despite the discontinuation of Sanofi’s diabetes programme, the research indicates that HA has significant potential in addressing chronic conditions like diabetes and obesity.
