Late Tuesday the FDA came through with an approval for mipomersen (Kynamro), an antisense drug advanced by Isis ($ISIS) and partnered with Sanofi's ($SNY) Genzyme. It's the second new drug approved recently for homozygous familial hypercholesterolemia (HoFH), a rare and dangerous form of high cholesterol.
The approval, which wasn't a sure thing, comes with some strings attached. The agency is requiring four postmarketing studies and wants the developers to carefully track the long-term safety of the drug.
"Kynamro, an injection given once a week, works with other lipid-lowering medications and diet to impair the creation of the lipid particles that ultimately give rise to LDL-C," said Eric Colman, M.D., deputy director of the Division of Metabolism and Endocrinology Products at the FDA's Center for Drug Evaluation and Research. As Isis explains on its website, the drug is designed to reduce LDL cholesterol by inhibiting the production of apo B, a protein that provides the structural core for all atherogenic lipids.
Mipomersen has had a troubled record. A few years ago Isis signed on Genzyme as a partner for the drug. Forbes' Matthew Herper noted in a scathing reassessment that Isis chief Stanley Crooke had been touting mipomersen as a potential successor to Lipitor, the biggest cash cow in pharma history. Crooke, reported Herper, was "too eager to hype experimental medicines and not willing enough to admit their flaws."
That shortcoming was shoved to center stage when the FDA, rather than Isis, revealed that the drug was linked to a higher risk of cancer and liver side effects--when its use was restricted to rare cases of homozygous familial hypercholesterolemia (HoFH).
A 9-to-6 advisory committee in favor of an approval only seemed to heighten uncertainty about the drug. And analysts had to consider a far more enthusiastic endorsement of Aegerion Pharmaceuticals' ($AEGR) competitor lomitapide (dubbed Juxtapid for commercial purposes). Add a negative opinion on mipomersen from a European Medicines Agency panel, and the confusion over the drug's future only grew worse, even though a positive FDA panel vote would normally indicate a near-term OK.
Nevertheless, it's a particularly important win for Sanofi as well as Genzyme, which has been positioned as the central player in the pharma giant's plans to develop more new drugs. In this environment, all new drug approvals are a cause for celebration. As for Isis, the approval triggers a $25 million milestone payment along with some long-awaited evidence that it is on the right development path.
"Today's FDA approval of Kynamro is great news for patients with HoFH who are in need of additional treatment options for this rare, and often under-diagnosed disease," said Genzyme's president and CEO, David Meeker, M.D. "As the leader in treatments for rare diseases, we are pleased to bring our expertise to HoFH patients living with this serious condition to better help them manage their disease."
Homozygous familial hypercholesterolemia is an extremely rare genetic condition characterized by dangerously high levels of LDL which can trigger a lethal set of cardiovascular conditions. Only about one in a million people get the genetic disease, making any therapies that can fight it worth six figures in the U.S. A significant percentage of patients in the small pivotal study Aegerion mounted demonstrated a spike in liver enzymes, a classic red flag for drug developers. A REMS program will be required to monitor patients and educate physicians.
- here's the press release from the FDA
- here's the release from Genzyme