This morning the regulatory and research team at Aegerion Pharmaceuticals ($AEGR) were hunkered down preparing for Wednesday's FDA panel review of their new drug for rare cases of homozygous familial hypercholesterolemia (HoFH), encouraged by an FDA review of lomitapide that focused considerable attention on the right kind of risk evaluation and mitigation strategy (REMS) that could keep the risk/benefit profile in proper proportion.
But one short step behind Aegerion is a similar drug program from Genzyme and Isis, with the FDA today publishing an internal review on the rival Kynamro (mipomersen), which also carefully scrutinized the proposed REMS while fretting over side effects, safety and discontinuation rates.
One big problem regulators had with Kynamro: Growths found in 3% of the patients in the drug arm, with 9 of the 23 neoplasms malignant. One analyst at Cowen, Eric Schmidt, told Bloomberg that the growths represented a new concern, raising a cloud over the program's chances. And Isis ($ISIS) shares swiftly plunged on the speculation over trouble ahead.
Noting a number of deaths and serious adverse events in the clinical studies of mipomersen, the FDA review concluded that a carefully crafted REMS would be needed to "ensure the benefits of a drug outweigh the risks." Balancing the needs of patients, who have limited therapeutic options, the reviewers wanted to make sure the REMS can keep the drug restricted to the tiny HoFH population and away from the broader community of hypercholesterolemia until more was known about its risks. And after endorsing the efficacy results seen in a 26-week study, reviewers outlined a risk-management program that could allow an approval.
"The REMS proposed above would support appropriate use of mipomersen, allowing it to be approved for use in the targeted patient population, a patient population with life threatening illness and limited therapeutic options, while protecting the larger hypercholesterolemic patient population," the FDA concluded.
The review noted that the average 25% reduction in LDL-C is significant, but there was a wide range of individual responses behind that group figure. And the dropout rate was worrisome.
"This high discontinuation rate from adverse events is problematic for a therapy that needs to be taken chronically," the FDA noted.
Mipomersen is an antisense oligonucleotide inhibitor designed to lower LDL-C. While its primary endpoint reflected a lower rate of reduction for LDL-C compared to Aegerion's lomitapide, the agency review also flagged concerns about potential liver damage that are likely to attract considerable attention from the panel.
Both lomitapide and mipomersen would be limited to use in a tiny population of patients, indicating that the developers have some six-figure price tags in mind that could drive hundreds of millions of dollars in sales. But there won't be any clear notion about revenue potential until the rivalry at the FDA shakes out and prices are announced.
- here's the FDA review (PDF)
- read the story from Bloomberg
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Big trouble for Isis: Shares plummet as FDA doc reveals safety concerns for Kynamro.
With input from @FierceBiotech