Novartis Resubmits Inclisiran NDA to FDA with New Manufacturing Site in Austria

Compiled by | river

Last December, the FDA rejected Novartis’s siRNA cholesterol-lowering drug Leqvio (inclisiran) due to the inability to complete the manufacturing facility inspection on schedule. Recently, the company announced that it has resubmitted the Leqvio application to the FDA and provided a new manufacturing site.

Leqvio is a PCSK9-targeting small interfering RNA (siRNA) therapeutic that exerts its mechanism of action by inhibiting hepatic PCSK9 synthesis. As a chronic disease medication, Leqvio requires administration only once every six months. Currently, the company is transitioning the drug product manufacturing of this therapy from a facility operated by contract manufacturer Corden Pharma in Italy to its in-house plant in Schaftenau, Austria. Reports indicate that the company had already initiated the technology transfer to the Austrian facility prior to the FDA's rejection. The company’s Chief Executive Officer confirmed that this transfer was completed in April of this year. Although Leqvio faced an FDA rejection in December of last year, it received regulatory approval in the European market at nearly the same time, becoming the first and only approved siRNA drug in Europe. At that time, the Italian facility served as its manufacturing site.

Leqvio, a core product acquired by Novartis from The Medicines Company for $9.7 billion in 2019, was expected at the time to rapidly enter the market and generate sales. At that time, some industry experts expressed concerns regarding the drug's value, as other PCSK9 antibody drugs—Amgen's Repatha and Sanofi and Regeneron's Praluent—had both failed to meet sales expectations due to price wars.

In addition to rejections related to manufacturing inspections, the COVID-19 pandemic has also impacted a pivotal trial for the drug. The pandemic slowed patient enrollment in the UK, prompting Novartis to postpone the pivotal cardiovascular outcomes trial ORION-4 from 2024 to 2026.

Currently, data on Leqvio only indicate its ability to lower harmful cholesterol levels. However, the true objective of PCSK9-targeting antibody drugs should be to reduce serious cardiovascular events, such as myocardial infarction and stroke. In this regard, Leqvio requires further clinical trial data to substantiate this outcome.

Novartis launched Leqvio in Germany and Austria in February this year for patients at very high cardiovascular risk. The company has also signed a partnership agreement with the UK's National Health Service (NHS) to roll out the drug in the UK. In the absence of outcomes data, the company is discussing similar market access agreements with EU countries.

Reference: Novartis revives inclisiran U.S. filing by sidestepping FDA's manufacturing inspection concerns