Chiesi wins EC approval for lomitapide in children with HoFH

Chiesi Global Rare Diseases has secured European Commission approval to extend the use of LOJUXTA (lomitapide) to paediatric patients aged five years and older with homozygous familial hypercholesterolaemia (HoFH), a rare inherited condition characterised by severely elevated LDL cholesterol from birth. The decision follows a positive recommendation from the EMA's Committee for Medicinal Products for Human Use (CHMP) and adds to lomitapide's existing EU authorisation for adult HoFH patients, first granted in 2013.

HoFH is caused by mutations in both copies of the LDL receptor gene, leaving the body unable to clear LDL cholesterol from the bloodstream. Affected individuals can carry more than ten times the acceptable LDL-C level, driving premature atherosclerosis and cardiovascular events — often in childhood or early adulthood. The rarity of the condition and the severity of its consequences make any expansion of the treatment toolkit clinically significant.

Phase 3 evidence

The approval rests on data from APH-19, a Phase 3 open-label, single-arm, multicentre study in 43 paediatric participants aged 5 to 17 years. The study met its primary endpoint, demonstrating a mean 53.5% reduction in LDL-C from baseline at week 24 (p<0.0001). Statistically significant reductions were also reported for non-HDL-C, total cholesterol, VLDL-C, apolipoprotein B, and triglycerides — all secondary outcomes. The full results were published in The Lancet Diabetes & Endocrinology in late 2024.

Adverse events were predominantly mild and consistent with lomitapide's established profile: gastrointestinal and hepatic in nature. Five patients (12%) experienced adverse events of special interest — two gastrointestinal and three hepatic. One serious treatment-emergent adverse event was recorded, an elevation in hepatic enzymes, which prompted two dose interruptions and two dose reductions. No new safety signals were identified.

Mitch Goldman, SVP Research & Development at Chiesi Global Rare Diseases, said the approval addresses a clear unmet need: "HoFH is a condition that can begin causing irreversible cardiovascular damage from the earliest years of life, and the unmet need remains for younger patients despite existing treatment options."

Market and competitive context

Lomitapide works by inhibiting microsomal triglyceride transfer protein (MTP), a mechanism distinct from statins, PCSK9 inhibitors, and LDL apheresis — all of which are used as part of standard-of-care combinations in HoFH. The HoFH treatment landscape has evolved considerably over the past decade. Evinacumab (Regeneron's Evkeeza), an angiopoietin-like protein 3 inhibitor, received EMA approval for HoFH in adults in 2021 and gained a paediatric indication in subsequent years, making it a direct comparator. Inclisiran, a small interfering RNA targeting PCSK9, is approved for adults but does not currently carry a paediatric HoFH indication in the EU.

Chiesi's move to secure a paediatric label for an established adult drug reflects a broader regulatory trend: orphan disease sponsors are increasingly pursuing age-range extensions using real-world registries and dedicated paediatric studies, supported by EMA paediatric investigation plan requirements. For HoFH specifically, treating children early — before vascular damage becomes irreversible — is now an explicit goal of the 2023 European Atherosclerosis Society consensus update.

With 31 affiliates worldwide and an orphan-disease-focused business unit, Chiesi is well positioned to commercialise the expanded label across European markets. The company will need to navigate access negotiations at the national level, where health technology assessment bodies apply varying cost-effectiveness thresholds for ultra-rare indications. Key near-term milestones include country-by-country reimbursement decisions and potential label extensions in other geographies.