Regeneron has chalked up a positive mid-stage clinical trial for evinacumab, a lipid-lowering antibody that could slot into its portfolio alongside Sanofi-partnered Praluent (alirocumab).
Evinacumab comes from the same R&D roots as alirocumab but is designed to work a little differently, targeting elevated triglycerides in the blood as well as other lipids such as low-density lipoprotein (LDL) cholesterol.
Elevated triglycerides can lead to inflammation of the pancreas as well as raising the risk of heart diseases such as atherosclerosis. In the Phase I trial, evinacumab was able to slash levels by 64% to 73%, far outperforming current treatments such as fish oils or fibrates which typically only reduce them by 20% to 50%.
The drug "could be combined with current oral medications for those patients with extraordinarily high triglycerides who often can't achieve safe levels with our usual medications," commented lead investigator Richard Dunbar of the University of Pennsylvania.
Evinacumab targets a different mechanism to Praluent and rival PCSK9 inhibitor Repatha (evolocumab) from Amgen, inhibiting angiopoietin-like 3 (ANGPTL3)--an inhibitor of lipoprotein lipase (LPL) responsible for the breakdown of triglycerides and other lipids.
Regeneron reported results of a trial of evinacumab in homozygous familial hypercholesterolemia (HoFH) earlier this year which found that adding the drug to standard cholesterol treatment such as statins also improved LDL-cholesterol reductions.
HoFH patients continue to have a major unmet need as they typically do not respond to standard lipid lowering therapies such as statins or even to PCSK9 inhibition, said Regeneron's chief scientific officer George Yancopoulos at the time.
"Although these data were from a small number of patients, we are encouraged by the additional 55% reduction in LDL cholesterol levels at week four on top of standard of care compared to baseline," he said recently.
Shares in Regeneron rose more than 5% yesterday after news of the positive triglyceride data emerged and investors started to look a little more closely at the prospects for evinacumab, which to date has been regarded as a somewhat speculative program. As recently as September, analysts at Credit Suisse were giving the drug only a 5% chance of approval in 2022.
The new data come at a time when Praluent and Repatha have yet to make significant headway in the market, despite blockbuster sales expectations. That is largely attributed to "significant reimbursement hurdles for physicians' offices and patients," according to Robert Terifay, Regeneron's executive vice president, commercial.
The challenges faced by the class were made clear when Pfizer took the decision to discontinue development of bococizumab, which was on course to be third to market, blaming an "evolving treatment and market landscape for lipid-lowering agents." Sales of Praluent were just $38 million in the third quarter while Repatha brought in $31 million for Amgen.
Having the capacity to tackle both LDL-cholesterol and triglycerides simultaneously could help encourage uptake of evinacumab if approved, although like the PCSK9 inhibitors it will still face the challenge of competing with an array of medicines that are extremely low cost.
Evinacumab grew out of a long-standing R&D partnership between Sanofi and Regeneron, but the French pharma giant decided not to opt in to co-develop evinacumab and Regeneron currently has sole rights to the drug. Sanofi is however entitled to mid-single-digit royalties on potential future sales.