6. Inclisiran

Novartis' PCSK9 drug inclisiran is back on the annual list of most anticipated launches after a pandemic-precipitated pause in 2020.

Drug: inclisiran
Company: Novartis
Used for: hypercholesterolemia
Est. 2026 sales: $2.01 billion

Novartis’ newly acquired inclisiran was originally supposed to get its U.S. approval by the end of 2020, but then COVID-19 hit.

In December, the FDA surprisingly issued a complete response letter over the PCSK9 drug’s application for patients who have elevated levels of bad cholesterol. Novartis characterized the FDA’s concerns as being over “facility inspection-related conditions” at an Italian plant belonging to its contractor, Corden Pharma—but not relating to inclisiran’s efficacy, safety or any other product-specific matters.

An on-site inspection had previously been set for May 2020, but the FDA stopped foreign inspections due to COVID. In the paperwork Novartis submitted, the agency found some “process control-related issues,” according to Novartis CEO Vas Narasimhan.

Inclisiran’s fate this year remains unclear. While the Swiss drugmaker expects to respond to the FDA’s requests around the second or third quarter, it’s not sure if the FDA will eventually want to inspect this facility, so “it’s difficult to comment on the timeline from there,” Narasimhan recently told reporters. But based on Novartis’ general expectation that the pandemic-related sales slowdown will lift by the second half of 2021, an approval for inclisiran by year-end is still possible.

RELATED: Novartis set to answer inclisiran's FDA rebuff by Q3. But what about an approval timeline?

In the meantime, Novartis management tried to put a positive spin on the delay, saying it would allow the company to potentially avoid a more difficult launch amid a pandemic and be better prepared when an approval does arrive.

With inclisiran’s U.S. regulatory fate hanging in the balance, it snagged an EU green light under the brand name Leqvio in December, six months ahead of schedule. The aforementioned Italian facility was part of the package Novartis used for this approval. The company expects the first EU prescriptions to come from Germany in February.

To ensure a smooth rollout in the U.K., Novartis signed a first-of-its-kind population-level agreement with the U.K. government. The initiative will tackle some “nonclinical barriers” ahead of Leqvio, including patient adherence and access, Novartis has said. That program is expected to launch in the third quarter.

RELATED: Inclisiran now has its cost-effectiveness report from ICER. Should Novartis be concerned?

Potentially better treatment compliance is a big selling point of inclisiran. Across inclisiran’s Orion clinical program, the drug posted a reduction of around 48% to 52% in LDL-C levels in different patient subgroups. That kind of efficacy is generally viewed as on par with the two existing PCSK9 antibodies—Amgen’s Repatha and Sanofi and Regeneron’s Praluent. But those two options are self-administered by patients every two to four weeks, while inclisiran is injected by a healthcare professional every six months after two initial loading doses.

After entering the U.S. market in 2015, Praluent and Repatha faced pricing pushback from cost-effectiveness watchdogs and payers, and their sales today are still dwelling at levels far below the megablockbuster mark industry watchers originally projected. In the third quarter of 2020, Repatha—the better performer of the two—brought in sales of $205 million on 22% year-over-year growth.

To sidestep the pricing scrutiny that its in-class predecessors experienced, Novartis has said from the outset that it would price inclisiran within the cost-effectiveness range that’s been proposed before. And a new report by the Institute for Clinical and Economic Review has pegged inclisiran’s cost-effective price at between $3,600 and $6,000 a year, in line with the $5,400 and $5,850 list prices the two antibody drugs currently bear.

As of January, EvaluatePharma estimated combined Repatha sales for Amgen and partner Astellas to be $1.97 billion in 2026, and global Praluent sales for Sanofi and Regeneron to be just $669 million. Both are lower than the estimated $2.01 billion for inclisiran at that point in time.

6. Inclisiran