siRNA Modality: Novel Therapeutics on the Horizon Therapies

Author: Neha Anand, Senior Market Analyst, Hanson Wade Intelligence

siRNAare here to Stay

The discovery of siRNA as a drug launched novel paths towards development of innovative therapies. However, regardless of initial enthusiasm, the clinical application of siRNA did not set off at the time owing to challenges such as lack of site-specific delivery system and instability of siRNAs. But researchers worked hard to overcome these obstacles and thereby, conquered the stagnation phase. With four siRNA drugs namely, Patisiran, Givosiran, Lumasiran, and Inclisiran now already approved and others in later stages of the clinical pipeline, siRNA is proving to be a promising therapeutic modality. These late-stage pipeline drugs are based on different delivery systems and are targeting metabolic diseases, haematology, infectious disorders, cancer, eye diseases, and others. Alnylam Pharmaceuticals is the key market player engaged in the development of siRNA therapies drugs and oversees three of the four siRNA approved till date.

Novel Delivery Systems Fuelled the Development

The successful clinical applications of siRNA drugs had been limited by factors such as quick degradation, rapid renal clearance, and reduced cellular uptake. However, lipid and polymer-based nanoparticle siRNA delivery systems demonstrated effectiveness. Liposomes were the first nano drug delivery systems that effectively transformed into actual clinical applications. The second and third generation of liposomes possessed the ability to identify specific receptors and improve the liposome stability. These nano systems permitted the co-delivery of siRNAs with chemotherapeutics realizing synergistic anti-cancer effects in vivo. Also, siRNAs are integrated into a delivery system by electrostatic interactions with its cationic components, rendering siRNA protection, high loading efficiency and enables siRNAs release into the target cells cytoplasm.

Surge of Investments

Since January 2020, some of the biggest siRNA-based strategic alliances have occurred at global level in terms of value. In March 2020, AstraZeneca collaborated with Silence Therapeutics and invested US$4.1bn to develop siRNA therapeutics for cardiovascular, renal, metabolic and respiratory diseases. In July 2021, Alnylam Pharmaceuticals signed a partnership deal with PeptiDream for US$2.2bn. In October 2021, Hansoh Pharma, a Chinese firm formed alliance with Silence Therapeutics and OliX Pharma to develop siRNA-based therapeutics. Hansoh made an upfront payment of US$16m and Silence Therapeutics was entitled to receive up to US$1.3bn in additional development, regulatory and commercial milestones. These deals indicate the possible opportunities that siRNA-based therapeutics can create for pharmaceutical firms. However, these high value strategic alliances in the siRNA space are in the initial stages of development.

Thus, with the strong backdrop, the global siRNAs market is poised to expand. These therapies will fulfil the existing long-term unmet need especially for rare indications.

For further reading, download our recent report ‘Biopharma Deals in RNA Space: A post-Covid Landscape Review‘ where you’ll gain valuable insights on the main industry movement in the RNA space and development of RNA therapies.