Alynlam Pharmaceuticals and The Medicines Company reported positive initial results from their ongoing Phase 1 clinical trial with their injectable cholesterol-lowing drug, ALSN-PCSsc, at the ESC Congress 2015 held in London, August 29 – September 2.
Alnylam Pharmaceuticals and The Medicines Company reported positive initial results from their ongoing phase 1 clinical trial with their injectable cholesterol-lowing drug, ALSN-PCSsc, at the ESC Congress 2015 held in London, August 29 to September 2.
In contrast to anti-PCSK9 monoclonal antibodies (MAbs) that bind to PCSK9 in blood, ALN-PCSsc is a first-in-class investigational medicine that acts by turning off PCSK9 synthesis in the liver. Plus, the drug will likely only have to be administered 2 to 4 times a year.
In the phase 1 study, ALN-PCSsc resulted in an up to 83% lowering of LDL-C. Similar reductions in LDL-C were seen in patients on and off concomitant statin therapy, according to the 2 companies.
“Remarkably, significant and clamped lowering of LDL-C is achieved for over 140 days after a single dose…Accordingly, we believe that these results support a quarterly, and possibly bi-annual, low volume subcutaneous dose regimen for further development,” said Akshay Vaishnaw, MD, executive vice president of R&D and chief medical officer at Alnylam.
However, ALN-PCSsc and other PCSK-9 treatments, such as Praluent from Sanofi/ Regeneron and Repatha from Amgen, are controversial. “Regulatory agencies like the FDA get nervous when dealing with such a long-acting drug [ALN-PCSsc] because, should a rare adverse event actually be observed, the drug is not going to wash out anytime soon,” wrote John LaMattina, contributor to Forbes. “To ease this concern, the FDA will want to see long-term safety studies to be assured that serious idiosyncratic reactions don’t arise.”
ALN-PCSsc is further challenged by the fact that Praluent, Repatha, and possibly a PCSK9 antibody from Pfizer, will already have been on the market for at least 5 years before the Alnylam drug. “By this point, Amgen and Sanofi/ Regeneron will have completed long-term cardiovascular outcome trials (CVOTs) that will not only add a huge amount of safety data for the established agents, but could also show that these drugs reduce heart attack and strokes even better than statins alone,” LaMattina wrote.
Still, in the phase 1 trial, ALN-PCSsc was generally well tolerated with no clinically drug-related significant adverse events to date, according to the 2 manufacturers. “Based on these positive results, we believe that ALN-PCSsc potentially represents an innovative, differentiated, and well-validated approach for the treatment of hypercholesterolemia,” Vaishnaw said.
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