3. Inclisiran

Existing PCSK9 drugs have largely disappointed in sales, but Novartis thinks it can do it differently with inclisiran, the centerpiece of its $9.7 billion acquisition of The Medicines Company. (Novartis)

Drug: inclisiran
Company: Novartis
Used for: high LDL cholesterol
Est. 2024 sales: $1.529 billion

Novartis basically paid $9.7 billion for cholesterol-lowering therapy inclisiran when it bought The Medicines Company last year. Is the price too high for a PCSK9-targeting drug, whose class has been suffering a slow launch? The Swiss drugmaker itself seems to think so, but there’s a chance it could prove the idea wrong.

Existing PCSK9 drugs—Amgen’s Repatha and Sanofi and Regeneron’s Praluent—have not lived up to their early hype. After initial reimbursement pushback and a price-cut match-up, the current annualized sales for the two marketed drugs combined are just $1 billion, with Repatha ahead at $168 million in the third quarter.

That's four years into their launches—and the Street had originally expected multibillion-dollar sales for each. In fact, the market is so underperforming that Sanofi has lost confidence and rejigged its Regeneron partnership by returning U.S. Praluent rights.

Inclisiran has put up comparable data on its ability to lower bad cholesterol. The new drug is different from the two antibodies in that it uses a small-interfering RNA to target PCSK9. It’s also given twice a year after two lead-in doses, whereas the two FDA-approved drugs are given every two weeks or once a month.

But Wolfe Research analyst Tim Anderson, M.D., previously argued that a convenience edge won’t be enough to turn the tide, suggesting “the commercial case—injectable drugs for a ‘silent’ disease, entering a highly-genericized category—would be challenging.”

It all comes down to execution, analysts from Evercore ISI and Jefferies said. But there's a high bar to clear: Evercore ISI’s Umer Raffat figures inclisiran needs to hit more than $2 billion in peak annual sales to justify the $9.7 billion purchase price. EvaluatePharma researchers say the drug could reach $1.529 billion in 2024.

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One key piece to inclisiran's launch puzzle will be cardiovascular outcomes data, which both Repatha and Praluent have. Although the new medication won’t have that data till 2024, when the Orion-4 trial is expected to deliver outcomes results, MedCo management has argued that LDL-c is already a validated marker to predict CV benefits—but it remains to be seen whether payers think the same.

In terms of marketing, Novartis is obviously a better owner for inclisiran than MedCo, what with the Big Pharma’s decadeslong CV experience with its valsartan franchise, including the fast-growing combination drug Entresto. Despite bearing different indications, Entresto prescribers amount to about 80% of prescribers of statins or existing PCSK9s in the U.S., Novartis CEO Vas Narasimhan, M.D., has said. That means the company only needs “an incremental few hundred reps” to field inclisiran. As for the ex-U.S. market, the existing team could cover about 90% of doctors, he said.

To kick things off, at the J.P. Morgan Healthcare Conference in January, Narasimhan and Britain’s National Health Service unveiled a “population-level agreement” that would make inclisiran available for high-risk cardiovascular disease patients upon its expected regulatory approval. Under the agreement, the drug will also be tested in a large-scale U.K. clinical trial in primary prevention, in which heart disease has yet to develop in at-risk patients.

In the U.S., MedCo—now Novartis—submitted the new drug application for inclisiran to the FDA in December 2019.

3. Inclisiran