Introduction and methods

Results of a 52 week open -label phase 2b study to assess long-term-safety, immunogenicity and LDL-c efficacy of monthly dosing with LIB003 a novel anti-PCSK9 recombinant fusion protein

Presented at the virtual EAS 2020 by Traci Turner (LIB Therapeutics and Metabolic & Atherosclerosis Research Center, Cincinnati, OH, USA).

LIB003 is a recombinant fusion protein consisting of a PCSK9-binding domain (adnectin) and human serum albumin. Small injection volumes are possible due to its high binding affinity to PCSK9, small size (77 kD) and highly solubility. Binding of LIB003 to PCSK9 prevents the interaction between PCSK9 and the LDL receptor. This results in increased recycling of the LDL receptor and decreased LDL-c levels.

A 12 week double-blind, randomized phase 2 trial, in which LIB003 150, 300, and 350 mg were given subcutaneously every 4 weeks, showed a stable reduction in LDL cholesterol of >70% and >80% of free PCSK9 at the 300 mg LIB003 dose. No further LDL-c reduction was observed at the highest dose.

Patients who had finished the phase 2 trial, entered the open-label extension phase 2b trial (n=32). 28 Patients had been on LIB003 in the parent trial. Enrollment limitation was due to drug availability. Patients were given 300 mg of LIB003 every 4 weeks for 52 weeks. This study evaluated the LDL-c efficacy, long-term safety and immunogenicity of LIB003 treatment.

Main results

• The mean reduction in LDL-c at 52 weeks of treatment was 64.1% (SD: 17.4, P<0.0001). The reduction in LDL-c was stable during the entire treatment period.
• Reduction in LDL-c from baseline to 52 weeks ranged from >30% to >80% per patient. There were no non-responders in the trial.
• From baseline to end of the treatment, mean unbound PCSK9 was stably reduced by 83.4% (P<0.0001).
• Lipoprotein(a) was lowered by 31.5% with LIB003 (P<0.0001), apolipoprotein B by 47.1% (P<0.0001).
• LIB003 was well tolerated: mild injection site reactions occurred in 5 patients at one single visit (1.4% of all doses received). Low level of anti-drug antibodies were detected but not associated with any safety or injection site reaction and had no impact on treatment.

Conclusion

LIB003 was safe and highly effective in reducing LDL-c, PCSK9, lipoprotein(a), and apolipoprotein B levels, when given every 4 weeks subcutaneously during a one-year-period. Larger and longer phase 3 trials with 300 mg LIB003, four-weekly subcutaneous injections to fully assess efficacy and safety are in progress.

-Our reporting is based upon on the information provided at the EAS 2020 congress-

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