A few months ago, we wrote an article about two drugs for Homozygous familial hypercholesterolemia (HoFH), a rare genetic lipid disorder. One of the drugs was Aegerion’s Juxtapid (lomitapide). The other was Isis Pharmaceuticals’ Kynamro (mipomersen). It was early November and Juxtapid had just been given FDA approval. It was a good day for patients with HoFH, a great day for Aegerion investors, and a lousy day for Isis Pharmaceutics investors.
That was then, this is now
What a difference a few months makes. On Monday, Isis’ drug (in partnership with Genzyme), received approval from the FDA to treat HoFH. This is not good, but great news for patients with HoFH. They now have choice between the two drugs based on the own or their clinician’s preferences. It is also great news for Isis Pharmaceutical investors. That company’s stock has bounced back. (see graph on left)
And how is Aegerion’s stock doing? It is doing just fine (see graph on right).
Efficacy and Safety of Kynamra
The FDA approval for Kynamro was based on a randomized, double-blind, placebo-controlled, multi-center trial enrolled 51 patients age 12 to 53 yrs. Patients were randomly assigned to Kynamro 200 mg subcutaneously every week (n=34) or placebo (n=17) for 26 weeks. At the end of the study, the mean percentage change in LDL cholesterol concentration was significantly greater with Kynamro (-24.7%, 95% CI -31.6 to -17.7) than with placebo (-3.3%, -12.1 to 5.5; p=0.0003).
According to Isis’and Genzyme’s press release, safety data for Kynamro was based on pooled results from four Phase 3 clinical trials. The most common adverse reactions in patients treated with Kynamro that led to treatment discontinuation and occurred at a rate greater than placebo were: injection site reactions (5.0%), alanine aminotransferase (ALT) increased (3.4%), flu-like symptoms (2.7%), aspartate aminotransferase (AST) increased (2.3%), and liver function test abnormal (1.5%).
Homozygous familial hypercholesterolemia (HoFH)
HoFH is a rare genetic lipid disorder resulting in an accumulation of low-density lipoprotein (LDL-C) in the blood. Patients with untreated HoFH have extremely high LDL-C levels, typically between 400 mg/dL and 1,000 mg/dL. These patients are at severely high risk for premature cardiovascular events, such as heart attack or stroke.
The current treatment options for these patients include dietary modifications, lipid-lowering agents (e.g., statins), and in many cases, regular and costly LDL-apheresis is necessary. These treatments are often ineffective in reducing LDL-C to recommended levels in patients with HoFH. Another form of FH, heterozygous FH can usually be treated with statins and diet modification.
1. Raal FJ, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010 Mar 20;375(9719):998-1006.
Genzyme/Isis have set the price of Kynamro at $175,000. That is much cheaper than Juxtapid’s current pricetag of $235,000 - $295,000. How this all plays out with patients’, insurers’, and investors’ pocketbooks remains to be seen but the ones most likely to benefit will continue be the patients.