Alnylam Pharmaceuticals' zilebesiran, an RNAi-based therapy targeting hypertension, has been awarded an Innovation Passport by the UK's Medicines and Healthcare products Regulatory Agency (MHRA). This designation aims to accelerate access to promising new medicines within the National Health Service (NHS). The passport ensures that zilebesiran will be reviewed under the Innovative Licensing and Access Pathway (ILAP), potentially reducing the review time to 150 days.
Zilebesiran (formerly ALN-AGT) represents a new class of gene-silencing drugs designed for the treatment of chronic diseases with less frequent dosing, which could improve patient adherence. Similar to Alnylam and Novartis' Leqvio (inclisiran), a PCSK9-targeting RNAi drug for high cholesterol, zilebesiran offers the potential for twice-yearly or less frequent administration.
Mechanism of Action and Clinical Development
Zilebesiran targets angiotensinogen (AGT), a key component of the renin-angiotensin-aldosterone system that regulates blood pressure and fluid balance. Alnylam anticipates that zilebesiran could effectively manage hypertension with dosing as infrequent as two or four times per year. A Phase 1 trial demonstrated that a single injection of zilebesiran was well-tolerated and improved systolic blood pressure over 12 weeks.
The ongoing Phase 2 KARDIA-1 trial is evaluating zilebesiran in patients with mild-to-moderate hypertension. The study is enrolling adults whose blood pressure is not adequately controlled by standard medications. Results from the KARDIA-1 trial are expected early next year, slightly delayed due to patient enrollment disruptions caused by COVID-19 and the conflict in Ukraine.
Potential Impact on Hypertension Management
If approved, zilebesiran could provide a valuable alternative for the 15 million individuals in the UK living with hypertension. Currently, hypertension treatment primarily involves daily oral medications such as angiotensin II antagonists, calcium antagonists, and diuretics. A significant portion of these patients remain inadequately treated, highlighting the need for novel therapeutic options.
Brendan Martin, Alnylam's commercial innovation lead, emphasized the importance of early dialogue with health technology assessors to facilitate faster access to innovative treatments. He also expressed support for the UK Life Sciences Strategy and the ILAP pathway, which aims to accelerate the uptake of important new medicines.
The ILAP pathway mirrors the EU's Priority Medicines (PRIME) pathway by offering a fast-track review process. However, ILAP also incorporates funding considerations through the involvement of NICE, the Scottish Medicines Consortium (SMC), and the All Wales Therapeutics and Toxicology Centre (AWTTC).
