Aegerion shares surge on FDA review of rare cholesterol disease drug

Investors were cheered somewhat by the FDA's review of Aegerion's lead rare disease drug lomitapide in the lead-up to this week's meeting of a panel of outside experts. The agency's internal critique has just been posted, supporting the clinical efficacy argument that the company presented from its small Phase III pivotal study of homozygous familial hypercholesterolemia (HoFH) but fretting over the drug's potential impact on the liver--a red flag in safety reviews.

The lengthy, dispassionate review included a detailed recount of the adverse events counted in the clinical program for lomitapide, but also suggested that the right kind of risk evaluation and mitigation strategy--REMS--could effectively guard against risk factors.

The right REMS "would support appropriate use of lomitapide, allowing it to be approved for use in the targeted patient population, a patient population with life threatening illness and limited therapeutic options," the FDA concluded, according to a report from Bloomberg.

"Although 6 (21%) of the 29 subjects discontinued early, it is notable that all discontinuations occurred within the first 6 months of dosing (during the titration period) and that all remaining subjects tolerated at least a year of additional dosing," noted the FDA reviewer, who seemed supportive of Aegerion's efficacy claim. "Data from Study UP1002/AEGR-733-005 (the pivotal Phase 3 trial) have demonstrated that  lomitapide was effective in reducing LDL-C, total cholesterol, Apo B, triglycerides, nonHDL-C, and VLDL-C in patients with HoFH after 26 weeks of treatment when used as an adjunct to a low-fat diet and other lipid-lowering therapies with or without LDL apheresis. The reductions were maintained through Week 56…The bottom line, in my opinion, is that many subjects can demonstrate large LDL-C reductions that, in many cases, are sustained. If approved, individual risk/benefit assessments would need to be made by practicing clinicians; this assessment may be different for those who exhibit more-erratic LDL-C profiles."

The news of the review quickly pushed up its share price by 13%, which quickly slid to half that level as investors digested the full review. Lomitapide is an MTP inhibitor, the first drug up for regulatory action in that class.

Aegerion CEO Marc Beer has been counting on an approval to complete a turnaround he launched a little more than two years ago, when he took the helm. He quickly focused the biotech on lomitapide and then took the company public. And he believes that an approval would put the biotech on the path to profitability by 2014.

Even with an approval, though, a lot could happen between now and 2014. Genzyme and Isis ($ISIS) are closing in on their application for mipomersen for the same condition, with a decision expected in January, and a slate of developers have big programs to advance PCSK9 drugs that could radically slash LDL levels.

- here's the FDA review (PDF)
- read the story from Dow Jones
- get the report from Bloomberg