Familial hypercholesterolemia is a genetic disorder characterized by very high levels of low-density lipoprotein cholesterol (LDL-C), or "bad" cholesterol in the blood, leading to cardiovascular disease. The number of copies of the gene determines the severity of the disease: People with two copies of the gene (the homozygous form) suffer severe cardiovascular disease in childhood, while those with just a single copy of the gene (the heterozygous form) suffer from early heart disease in their 30s or 40s. The homozygous form occurs in 1 in every million individuals, while the heterozygous form is found in 1 in every 500 people.

The market leader for familial hypercholesterolemia therapies is Aegerion Pharmaceuticals (NASDAQ: AEGR). Aegerion's lomitapide treatment, Juxtapid, for the treatment of homozygous form of the disease, was approved by the Food and Drug Administration in December. The European version of the drug, Lojuxta, is expected to launch in the third quarter, following anticipated approval in August.

While still early days for the launch, Aegerion Pharmaceuticals has rapidly acquired patients using the therapy. As of its recent report, the company had 215 on active therapy with a total of 463 prescriptions globally. With a reported treatment cost of $250,000, the company has the potential to report $53 million in revenue. Going forward, the company is looking to boost the number on therapy to 3,000 in the U.S. and 15,000 globally. These figures run contrary to the reported frequency of the disease in the literature by a factor of 10, but the company sounded confident that the prevalence of the disease was much higher than is currently reported.

Genzyme, a Sanofi (NASDAQ:SNY) company, partners with Isis Pharmaceuticals' (NASDAQ:IONS) on Kynamro, which was approved in the U.S. in late January to treat homozygous familial hypercholesterolemia. In a study of 58 patients, Kynamro reduced bad cholesterol levels by 25%. However, in additional safety studies, 18% of patients stopped the treatment, suggesting a relatively poor tolerance to the therapy. Aegerion Pharmaceuticals' Juxtapid had a higher percentage of patients staying on therapy, with nearly half of those on the study benefiting from a 50% drop in LDL-C levels.

Isis Pharmaceuticals earned a $25 million milestone payment from Genzyme following the FDA approval. No hard figures were reported on uptake or market share, but in response to analysts, Isis said it was "very positive" on its position in the marketplace and against the competition, and expect to comment later in the year on its performance. Where Genzyme and Isis hold an edge over Aegerion is in pricing: Kynamro has a treatment price of $176,000 versus the $250,000 for Juxtapid. This could be key where pricing becomes critical and insurance companies push for cheaper options, even if patient tolerance is less.

Amgen (NASDAQ:AMGN) is working on therapy under the designation AMG 145 to treat the more common heterozygous familial hypercholesterolemia. AMG 145 is a human monoclonal antibody that inhibits Proprotein Convertase Subtilisin/Kexin Type 9, or PCSK9. Amgen's CEO, Robert Broadway, commented on the "great promise" of this emerging late-stage pipeline treatment, "to impact the incidence of cardiovascular disease," and considered AMG 145 could be one of the first molecules to address the need for people with hypercholesterolemia to treat the disease.

In November, phase 2 studies evaluating AMG-145 demonstrated a significant reduction in bad cholesterol levels after 12 weeks compared to control treatments, either given as a single therapy or in combination with a statin therapy, with reductions of 50%-70% in LDL-C. Additional phase 3 data is expected in the first quarter of 2014. Amgen has attributed the considerable rise of $302 million in R&D expenditure for 2012 in part to the late-stage clinical program for AMG 145, so the company has allocated considerable resources to the therapy's development.

The bottom line
It will probably be later in the year before we know Juxtapid and Kynamro's relative positions in the homozygous familial hypercholesterolemia market. This is a rare disease, which will make it a scramble between Genzyme/Isis and Aegerion for market share. Aegerion had guided for revenue of $30 million to $35 million for the rest of the year, but this should be significantly higher in 2014 if the number of patients on treatment exceeds the 250 to 300 estimates by year's end, as they are expecting to do.

Early next year will be big for Amgen. AMG 145 has shown early promise, and the company hasn't skimped on costs for the therapy's latest phase 3 trial. AMG 145 treats the more prevalent form of the disease, and for now, has a more open field to play in. Genzyme and Isis Pharmaceuticals are currently enrolling heterozygous sufferers for a Kynamro study, although results from this study are unlikely to be ready until late next year at the earliest.