Investors in The Medicines Company have Sept. 2 circled in red on their calendars. That's the day the company plans to report the first pivotal results from late-stage studies of its experimental cardiovascular drug, inclisiran.
Success would test the Parsippany, New Jersey-based biotech's all-in bet that it can compete in a market currently led by larger drugmakers Amgen and the team of Sanofi and Regeneron.
Wall Street analysts are expecting inclisiran to perform at least as well in lowering cholesterol as similarly acting drugs Repatha and Praluent, with the added benefit of twice a year dosing compared to once- or twice-monthly for the two approved products.
Falling short of that mark, or detecting a safety signal, would be devastating for The Medicines Company, which shed itself of a portfolio of drugs primarily used in hospital settings to finance the clinical program for inclisiran.
Along with selling off marketed lines like Angiomax and Kengreal, The Medicines Company raised at least $650 million from investors in the past three years to get inclisiran over the finish line, including a $150 million share sale in June 2019.
The setting for the big reveal will be the European Society of Cardiology meeting, where results of a trial called ORION-11 will be part of a session on cardiovascular prevention. That trial enrolled 1,600 patients with a history of heart disease or at high risk, testing inclisiran or a placebo on top of other lipid-lowering therapies. The trial's primary comparison measures low-density lipoprotein, or "bad cholesterol," 15 months after the first dose.
Executives said topline results will probably be available before the Sept. 2 presentation in Paris, although it will likely only state whether inclisiran was able to show a statistically significant reduction in LDL. Officials declined BioPharma Dive's request for an interview for this story.
Like Amgen's Repatha and Sanofi and Regeneron's Praluent, inclisiran targets a protein called PCSK9 that is essential to LDL metabolism in the liver. The difference is that the marketed products, which are a type of biological called a monoclonal antibody, do so by binding to PCSK9. By contrast, inclisiran blocks the expression of genes that encode PCSK9.
The two antibodies have set a high bar for inclisiran. In this same population with atherosclerotic cardiovascular disease or risk factors, Repatha lowered LDL by an average of 57% more than placebo after 72 weeks in the FOURIER cardiovascular outcomes trial. Praluent performed similarly, leading to a 55% drop after 48 weeks in the ODYSSEY study.
The Medicines Company is confident inclisiran can come through. Long-term data from Phase 2 trials has detected LDL-lowering of more than 50% up to three years after treatment, with no safety signals. Based on those LDL reductions, the company predicted that in the ORION-11 population the risk of cardiovascular events would be reduced 31%, although that will likely need to be proven through a long-term outcomes study, as Amgen did with FOURIER and Sanofi and Regeneron did with ODYSSEY.
Repatha and Praluent both reduced the risk of cardiovascular death and complications by 15%, similar to the combination of Zocor and Zetia, now off-patent drugs that reduced the risk of heart attacks by 13% and strokes by 21% in the IMPROVE-IT trial. The modest improvement is one of the reasons the prices of both Repatha and Praluent have been cut from their initial prices of about $14,000 to around $6,000 a year.
The Medicines Company may have two advantages. The first is that inclisiran, a type of drug called an oligonucleotide, may be cheaper to produce than antibodies, and thus may be profitable at a lower price.
"They talk about how they have a lot more flexibility around pricing," Dara Lundon, an analyst with Evercore ISI, said in an interview with BioPharma Dive.
Inclisiran also would not need to be refrigerated as antibodies are, potentially reducing distribution costs.
The second is the dosing frequency, which is twice a year once patients hit the maintenance phase. In the past, executives have said this could easily correspond with visits to cardiologists, meaning patients would not have to remember to take the drug as they do with PCSK9s or statins.
The exact value of twice a year dosing to patients, physicians or payers is an unanswered question, though.
Ethan Weiss, a cardiologist at University of California-San Francisco, told BioPharma Dive: "I don't see taking 24 injections a year as a significant problem for my patients. In some ways, the cadence of it is good and they can remember it."
Price could emerge as the most compelling factor. "With everything else, cost ends up being the big or final arbiter, and in this case it probably will be as well," he added.
The track record of Repatha and Praluent prove Weiss' point well. Both drugs launched to blockbuster sales expectations, yet struggled with resistance from insurers on price and low patient uptake. Even now, four years on from the drugs' market arrival and after multiple price adjustments, revenue earned from each remains modest.
September's results will give investors an answer to whether The Medicines Company's bet can succeed in the clinic. But whether the biotech has a profitable future ahead might depend just as much on whether it can learn from Amgen, Sanofi and Regeneron's commercial missteps.