The European Medicines Agency (EMA) approved Leqvio, the brand name of inclisiran, for the treatment of adults with hypercholesterolemia or mixed dyslipidemia late last year. A week later, an attempt to win approval in the US was thwarted when the US Food and Drug Administration (FDA) issued a complete response letter because of “unresolved facility inspection-related conditions.”
Novartis began transferring production from a Corden Pharma plant to its own facility in Schaftenau, Austria before the FDA rejection. The transfer of manufacturing to the in-house site enabled Novartis to refile in July without waiting for the resolution of the situation that sank its original filing.
Basel-based Novartis was in a position to use Schaftenau as the production plant in the FDA filing because of its earlier decision to invest to bring upstream and downstream manufacturing in-house.
Unlocking new indications
Talking to investors on a July 21 quarterly results conference call, Novartis CEO Vas Narasimhan said the investment in in-house manufacturing reflected a desire to unlock new indications for Leqvio.
“Our goal is to drive significantly down the cost of goods to enable large-scale use of the medicine in the secondary prevention study, and eventually, perhaps, in the primary prevention study,” said the CEO.
The first filings for approval of Leqvio in the US and Europe cover the use of the medicine in patients who have high cholesterol despite taking the maximum dose of a statin. A much larger opportunity and patient population awaits Novartis if it can show Leqvio is beneficial to healthier patients.
Novartis is running a phase 3 clinical trial in people who already have cardiovascular disease, a group known as secondary prevention patients. Working with England’s National Health Service, Novartis is also hoping to show Leqvio is beneficial to patients who are at very high risk of having their first cardiac event.
Persuading payers to cover the use of Leqvio in those larger, lower-risk patient groups could be a challenge for Novartis. The investment in in-house manufacturing may enable Novartis to rise to that challenge by bringing down the cost of goods sold, enabling the company to lower the price without eating into its profit margin.
The more immediate concern is whether the FDA will approve Leqvio. Narasimhan said the new site of production, which is where Novartis does secondary manufacturing for drugs such as Cosentyx, was recently remotely inspected and approved by the FDA in another context.