Abaloparatide (Tymlos)

Safety Summary

In the ACTIVE trial (N=822 abaloparatide, N=820 placebo), the most common adverse reactions (≥2%) were hypercalciuria (11% vs 9%), dizziness (10% vs 6%), nausea (8% vs 3%), headache (8% vs 6%), palpitations (5% vs 0.4%), fatigue (3% vs 2%), upper abdominal pain (3% vs 2%), and vertigo (2% vs 2%). Injection site reactions during the first month: redness 58% vs 28%, edema 11% vs 3%, pain 10% vs 7%. Discontinuation due to adverse events: 10% abaloparatide vs 6% placebo (FDA label NDA208743). In the men's trial (ATOM), common adverse reactions included injection site erythema (13% vs 5%), dizziness (9% vs 1%), arthralgia (7% vs 1%), and injection site swelling (7% vs 0%) PMID 36190391. Cardiovascular safety analysis showed transient HR increase (mean 7.9 bpm at 1 hour post-dose) that resolves within 4 hours, with no increase in serious cardiac AEs or MACE. Time to first MACE+HF was actually significantly longer with abaloparatide vs placebo (HR 0.30, p=0.02) PMID 32658264. Anti-drug antibodies developed in 41% of women at 18 months and 25% of men at 12 months, but had no clinically significant impact on efficacy or safety (FDA label NDA208743). A single case report described pseudoxanthoma elasticum (PXE) developing in a genetically predisposed patient (heterozygous ABCC6 mutation) 6 weeks after starting abaloparatide PMID 40606685.