MSD, Ionis trumpet lipid-lowering drug data

Two pharma companies developing lipid-lowering drugs, MSD and Ionis, have reported positive phase 3 data that open the way for regulatory filings in the coming months.

First up, MSD, which chalked up its third positive phase 3 trial for oral PCSK9 inhibitor enlicitide decanoate (formerly MK-0616), in a wider patient population than its two earlier studies in the CORALreef programme.

The CORALreef Lipids trial in patients with elevated cholesterol (hypercholesterolaemia) at risk of atherosclerotic cardiovascular disease showed that enlicitide achieved a statistically significant and "clinically meaningful" reduction in LDL-cholesterol compared to placebo at 24 weeks, its primary endpoint.

That was backed up by significant reductions in secondary risk factors for heart disease, including non-HDL-cholesterol, ApoB, and LP(a), according to lead investigator Ann Marie Navar of UT Southwestern Medical Center.

MSD – known as Merck & Co in the US and Canada – previously reported two positive phase 3 trials, one in inherited disorder heterogeneous familial hypercholesterolaemia (CORALreef HeFH) and another comparing enlicitide to other oral therapies as additional therapy for people with hypercholesterolaemia who are struggling to meet their treatment targets with statin therapy alone (CORALreef AddOn).

The third study encompassed a much broader group of patients, including those who had been treated with stable cholesterol-lowering therapies, including at least a statin, or who had documented statin intolerance.

Armed with the data, MSD now intends to start discussions with regulators with a view to filing enlicitide for approval, putting it firmly in the lead among drugmakers developing oral drugs against PCSK9, ahead of nearest rival AstraZeneca, whose AZD0780 started phase 3 testing earlier this year.

Currently available PCSK9-targeting therapies are Amgen's Repatha (evolocumab) and Sanofi/Regeneron's Praluent (alirocumab), both antibodies dosed monthly, and Novartis' small interfering RNA therapy Leqvio (inclisiran), which can be given twice a year.

"Enlicitide, designed to deliver antibody-like efficacy, is the first oral macrocyclic peptide PCSK9 inhibitor with clinically meaningful and statistically significant LDL-cholesterol lowering in phase 3 trials," said MSD's head of R&D, Dean Li.

"If approved, it has the potential to change the way we think about managing LDL levels, giving patients the possibility of a new option to help them meet their treatment goals."

Tryngolza triumph

Ionis, meanwhile, is looking at expanding the eligible patient population for already-approved apoC-III inhibitor Tryngolza (olezarsen) with new data in people living with severe hypertriglyceridaemia (sHTG).

Topline results from the pivotal Phase 3 CORE and CORE2 studies showed that Tryngolza achieved statistically significant reductions of up to 72% in fasting triglycerides in sHTG patients, as well as an 85% reduction in pancreatitis, one of the main complications of excessive triglyceride levels in the blood.

Last December, Tryngolza became the first FDA-approved drug therapy for familial chylomicronaemia syndrome (FCS), an ultra-rare disease causing high triglyceride levels that affects fewer than 5,000 people in the US. For comparison, around three million people are living with sHTG in the US, including more than a million who are considered high risk.

The company has previously suggested that approval for both FCS and sHTG could lead to Tryngolza achieving $1 billion-plus in annual sales, while analysts at Jefferies said that the strength of the CORE data had prompted them to raise their peak sales forecasts by $1 billion to $2.5 billion.

"Th[is] data [is] groundbreaking, demonstrating that olezarsen is the first therapy for sHTG to significantly reduce acute pancreatitis events," said Ionis' head of cardiovascular development, Sam Tsimikas.

The company has said it intends to file for the new indication for olezarsen, which has a list price of $595,000 a year in FCS, before the end of this year.

Image by Ahmad Ardity from Pixabay