April 25, 2025
4 min learn
Key takeaways:
- Two brokers concentrating on angiopoietin-like protein 3 safely lowered lipid ranges in section 2 trials.
- Solbinsiran and SHR-1918 will probably be additional studied in sufferers with excessive lipid ranges in section 3 trials.
CHICAGO — Two novel brokers concentrating on angiopoietin-like protein 3 demonstrated security and lipid-lowering capabilities in section 2 trials, in line with findings introduced on the American Faculty of Cardiology Scientific Session.
Within the PROLONG-ANG3 trial, solbinsiran (Eli Lilly), an N-acetylgalactosamine-conjugated small interfering RNA, lowered apolipoprotein B in sufferers with combined dyslipidemia. In a section 2 trial of the monoclonal antibody SHR-1918 (Jiangsu Hengrui Prescription drugs Co.), the agent was related to reductions in LDL, triglycerides and different lipids in sufferers with suboptimally handled hyperlipidemia.
PROLONG-ANG3
PROLONG-ANG3 included 205 sufferers (median age, 57 years; 54.1% girls) with combined dyslipidemia. They have been randomly assigned 1:2:2:2 to solbinsiran 100 mg, solbinsiran 400 mg, solbinsiran 800 mg or placebo, Kausik Okay. Ray, FMedSci, director of the Imperial Centre for Cardiovascular Illness Prevention and the Imperial Medical Trials Unit and head of ICTU-World at Imperial Faculty London, mentioned throughout a presentation. The outcomes have been concurrently revealed in The Lancet.
Kausik Okay. Ray
“For many of us, most of our atherogenic cargo is LDL ldl cholesterol, and we’ve got fairly good remedies for that,” Ray mentioned throughout a presentation. “However there’s an entire group of individuals [who] have this extra ldl cholesterol cargo … the so-called triglyceride-rich lipoproteins. For these sufferers, we actually haven’t seen efficient therapies to cut back that and due to this fact cut back the danger of cardiovascular occasions. … If we’ve got lack of perform of ANGPTL3, not solely do we’ve got a decrease degree of ANGPTL3, however we’ve got decrease ranges of an entire host of lipoproteins — triglycerides, LDL, non-HDL, ApoB … and a decrease threat of heart problems, suggesting this is a vital goal. … In preclinical research, solbinsiran lowered messenger RNA for ANGPTL3 and in addition circulating ranges of ANGPTL3. After we moved on to check that in people, we may see {that a} single injection of solbinsiran in a dose-dependent vogue produced discount in triglycerides.”
The first end result was % change in ApoB at 180 days. The placebo-adjusted % change in ApoB at 180 days was –2.8% (95% CI, –15.5 to 11.9; P = .69) for solbinsiran 100 mg; –14.3% (95% CI, –23.6 to –3.9; P = .0085) for solbinsiran 400 mg and –8.3% (95% CI, –18.3 to 2.9; P = .14) for solbinsiran 800 mg, in line with the researchers.
The outcomes for solbinsiran 400 mg have been sustained to 270 days, Ray mentioned.
In contrast with placebo, solbinsiran 400 mg additionally lowered angiopoietin-like protein 3 (ANGPTL3) at 180 and 270 days, triglycerides at 180 and 270 days, VLDL at 180 and 270 days, LDL at 180 days, non-HDL at 180 and 270 days and HDL at 180 and 270 days, he mentioned.
As well as, solbinsiran 400 mg and 800 mg lowered hepatic fats fraction at 180 days (P < .0001 and P = .0013, respectively), he mentioned.
There have been no deaths and few severe adversarial occasions. The charges of treatment-emergent adversarial occasions have been 60% within the solbinsiran 100 mg group, 52% within the solbinsiran 400 mg group, 44% within the solbinsiran 800 mg group and 65% within the placebo group, in line with the researchers.
“Solbinsiran was nicely tolerated with an especially reassuring hepatic security profile,” Ray mentioned in the course of the presentation. “The 400 mg dose specifically resulted in sturdy reductions in ANGPTL3 over 270 days, and this resulted in vital reductions in ApoB, triglycerides, very low-density lipoprotein and non-HDL in sufferers with excessive residual threat for future heart problems. This means that this specific remedy deserves additional analysis in future research.”
Section 2 trial of SHR-1918
For the section 2 examine of SHR-1918, concurrently revealed within the Journal of the American Faculty of Cardiology, the researchers randomly assigned 333 sufferers with hypercholesterolemia who didn’t obtain optimum LDL after 4 to eight weeks of normal lipid-lowering therapies to placebo or SHR-1918 150 mg each 4 weeks, SHR-1918 300 mg each 4 weeks, SHR-1918 600 mg each 4 weeks or SHR-1918 600 mg each 8 weeks. The imply age was roughly 58 years and about 60% of sufferers have been males.
“LDL and triglycerides are necessary threat elements for CVD,” Xiaojie Xie, MD, PhD, from the division of cardiology at State Key Laboratory of Transvascular Implantation Gadgets of The Second Affiliated Hospital of Zhejiang College College of Medication, in Hangzhou, China, mentioned throughout a presentation. “ANGPTL3 is concerned within the regulation of lipid metabolism and might cut back the clearance of triglycerides and LDL by inhibiting lipoprotein lipase and endothelial lipase. SHR-1918 is an ANGPTL3 monoclonal antibody developed to inhibit ANGPTL3 exercise, thereby reducing the serum ranges of triglycerides and LDL.”
At 16 weeks, in contrast with placebo, LDL was lowered by –21.7% in these assigned SHR-1918 150 mg each 4 weeks, –27.3% in these assigned SHR-1918 300 mg each 4 weeks, –29.9% in these assigned SHR-1918 600 mg each 4 weeks and –22.5% in these assigned SHR-1918 600 mg each 8 weeks (P < .0001 for all), Xie mentioned.
All SHR-1918 teams had decrease triglyceride ranges at 16 weeks in contrast with placebo (P < .0001 for all), she mentioned.
Xie mentioned all doses of SHR-1918 conferred absolute reductions in LDL, triglycerides, ApoB and ApoA-I.
The SHR-1918 teams all had lowered non-HDL at 16 weeks in contrast with placebo (P < .0001 for all), however there was no impact on lipoprotein(a), Xie mentioned.
Therapy-emergent adversarial occasions have been comparable between the teams, in line with the researchers.
“SHR-1918 demonstrated favorable efficacy in decreasing each LDL and triglyceride ranges at reasonable or increased threat of atherosclerotic CVD sufferers, with a manageable security profile in the course of the core remedy interval,” Xie mentioned in the course of the presentation. “These findings help SHR-1918 as a possible therapeutic possibility for hyperlipidemia on commonplace lipid-lowering remedy.”
References:
Sources/Disclosures
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Ray KK, et al. Featured scientific analysis IV. Offered at: American Faculty of Cardiology Scientific Session; March 29-31, 2025; Chicago (hybrid assembly).
Disclosures:
PROLONG-ANG3 was funded by Eli Lilly. The SHR-1918 examine was funded by Jiangsu Hengrui Prescription drugs Co. Ray reviews monetary ties with quite a few pharmaceutical firms, together with consulting for Eli Lilly. Xie reviews no related monetary disclosures. Please see the research for all different authors’ related monetary disclosures.
