The Medicines Co. and partner Alnylam Pharmaceuticals have presented new evidence supporting the long-term use of their RNA-based cholesterol lowering therapy inclisiran, which is meant to be a longer lasting alternative to a new crop of heart drugs called PCSK9 inhibitors.
At a medical meeting in Miami, Medicines Co. (NASDAQ: MDCO) reported that 290 patients on inclisiran in a long-term open-label study, ORION-3, saw their LDL-C or “bad” cholesterol levels lowered by an average of 51.4 percent with up to three years of follow-up.
Patients in the study have been on inclisiran for up to three years; no major safety problems have emerged. One patient in the study died from a stroke, and another saw a spike in liver enzymes, an indication of potential liver damage. Neither were attributed to the drug.
The data come just before the big reveal for the Medicines Co. Phase 3 data for inclisiran are expected later this year, with regulatory filings to come afterwards if all goes well. The data “bolsters confidence” in a positive result, wrote SVB Leerink analyst Joseph Schwartz. Medicines Co. shares climbed 5 percent in pre-market trading.
MedCo is aiming to show that inclisiran can provide a superior alternative to PCSK9 inhibitors, injectable antibody drugs that lower “bad” cholesterol. These drugs—alirocumab from Regeneron Pharmaceuticals (NASDAQ: REGN) and evolocumab (Repatha) from Amgen (NASDAQ: AMGN)—were hailed as a huge medical advance when approved in 2015, particularly in people who have bad reactions to standard-of-care statins or who can’t lower their cholesterol enough with them.
But PCSK9 blockers have struggled to sell because of their high prices. Insurers waited for evidence that the drugs could prevent heart attacks or strokes, too. And even when huge studies came through with at least some evidence of those measures, insurers still balked at reimbursing them. The companies have since cut prices and worked on creative deals with payers to try to change things.
Like alirocumab and evolocumab, inclisiran aims to lower the levels of the protein PCSK9; lower levels correlate with better clearance of LDL from the blood. Inclisiran uses RNA interference—a method of stopping genes from producing disease-causing proteins—to prevent the liver from making PCSK9 in the first place.
Even if inclisiran succeeds, it will likely face the same issues as alirocumab and evolocumab. But MedCo is betting that patient convenience will be a big factor in its favor. Alirocumab and evolocumab have to be administered once or twice a month, while inclisiran is being tested in doses given one or two times a year, which may help with patient compliance and lead to better control of their cholesterol. MedCo has bet heavily on that thesis, cutting other programs, raising debt, and restructuring to pay for the late-stage studies of inclisiran. The results from ORIOM-9, ORION-10, and ORION-11 later this year will show whether the gamble was worth it.
Today’s data, meanwhile, are also a boost for Alnylam (NASDAQ: ALNY), which discovered inclisiran and would get royalties on sales if it reaches the market. The company made history last year by winning the first-ever approval of a medicine that based on RNA interference, a method cells can use to silence a gene before it makes a harmful protein. But that medicine is for a rare disease called hereditary transthyretin amyloidosis. The ORION studies are the first big test of RNA interference in a broader population. “This dataset today might constitute one of the largest safety followups we’ve seen in the RNAi space,” wrote Evercore ISI analyst Umer Raffat. “And safety looks very good.”