Letter in Response to “Lomitapide: A Medication Use Evaluation and a Formulary Perspective” by Esba and Alharbi

As highlighted by Esba and Alharbi in their medication use evaluation of lomitapide at King Abdulaziz Medical City, adequate control of low-density lipoprotein cholesterol (LDL-C) remains an elusive goal for many patients with homozygous familial hypercholesterolemia (HoFH).[1] Most patients with HoFH do not reach their LDL-C target despite triple combination therapy with a statin, ezetimibe, and a PCSK9 inhibitor. In patients with HoFH, one or more fourth-line therapies, such as evinacumab, lipid apheresis, or lomitapide, are usually added to the therapeutic regime to improve LDL-C control.[2] Multiple factors, including efficacy, safety, accessibility, cost, and convenience, determine the choice of forth-line therapy. Because lomitapide is the only oral fourth-line option, it is particularly suited for use in patients living in remote areas without access to lipid apheresis or infusion services, as long as it is possible to monitor liver function tests and perform annual hepatic fibrosis screening.[3]None of the eight patients described by Esba and Alharbi were receiving lipid apheresis while being treated with lomitapide. Lomitapide and possibly evinacumab or hepatic transplantation were thus the only additional therapeutic options for these patients. Given the importance of lomitapide in the management of these patients, the reported LDL-C reduction of only 34.1% is disappointing, as it is substantially less than the 50% LDL-C reduction reported in the lomitapide registration study, and the 60% reduction reported in a real-world European observational cohort of 75 patients.[4,5]Because lomitapide inhibits lipoprotein assembly, it is effective in all patients with HoFH, irrespective of residual LDL receptor function. Therefore, it is important to understand the relatively poor and highly variable responses (from an 87.4% reduction to an increase in LDL-C) reported by Esba and Alharbi. Patients 2–5 have particularly poor responses at 1–3 months after initiating lomitapide. Additional data may be helpful in better assessing the overall efficacy of lomitapide. It would be useful to know the lomitapide dose at the time of evaluation and whether patients had already reached a maintenance dose or were still in the titration phase. Adherence and an uninterrupted medication supply are also crucial, as stated by former United States Surgeon General Dr. C. Everett Coop, "Drugs don't work in patients who don't take them" (1985). It would be interesting to see individual patient graphs showing all LDL-C measurements over the entire treatment course while also indicating the lomitapide dose and any periods of treatment interruption.Given the cardinal role that efficacy plays in any medication use evaluation, it is important that it be assessed as accurately and comprehensively as possible.