Daniel S. Levine
A rare disease patient group is calling on the U.S. Food and Drug Administration to reverse itself and “demanding” the agency approve an experimental therapy for familial chylomicronemia syndrome (FCS), an ultra-rare and potentially fatal disease.
At the end of August, the FDA notified Akcea Therapeutics and Ionis Pharmaceuticals that it would not approve the companies’ application to market Waylivra as a treatment for FCS. The FCS Foundation, a patient group, has sent a letter along with patient comments to the FDA seeking a meeting with regulators to discuss its decision and asking it to grant market approval for Waylivra. Akcea is a funder of the FCS Foundation, but the organization said it is acting independently from the company.
Separately, the wife of an FCS patient launched a petition campaign online to gather signatures to call on the FDA to approve Waylivra. As of September 7, more than 2,500 people had signed the petition.
“The main part of my frustration around this decision is that it is a rare disease and I feel they are applying a lot of the same rules that they are applying to other drug approvals to Waylivra. You can’t do that because of the rare nature of it, the population involved, and because the disease itself is not well understood,” said Melissa Goetz, co-founder and co-president of the FCS Foundation, and the mother of a daughter with FCS. “You have to hear what patients have to say about it. Otherwise, how can you make a well-informed decision about what the disease truly is like, how it impacts patients, and what they are willing to deal with in order to get relief from that? I think that’s really important.”
FCS is a condition in which patients cannot metabolize triglyceride-rich lipid particles called chylomicrons due to a deficiency in the enzyme lipoprotein lipase. As a result, people with FCS have high levels of triglycerides in the blood, which leads to a range of symptoms including permanent organ damage and potentially fatal attacks of acute pancreatitis. It affects 3,000 to 5,000 patients worldwide.
There had been expectation among investors and the patient community that the agency would act in the company’s favor after an advisory committee in May voted 12 to 8 to recommend its approval despite concerns about safety among some of the committee members. FCS patients did provide their input to the agency and expressed support for approval of the drug at the advisory committee meeting.
Akcea did not make public the FDA’s Complete Response Letter provided to the company to explain its decision.
“Regarding the CRL, we have stated publicly that the issues raised are consistent with what was discussed at the AdComm and are related to data on managing platelet levels and dosing,” the company said in response to a request for a copy of the letter. “We hope to address this with data from our ongoing Open Label Extension study and/or Early Access Program, but we will not know the specific path forward or if this will be a sufficient approach until we meet with the FDA. We hope to do that as soon as possible.”
Though FDA in documents expressed clear concerns that the drug could lower platelet counts of patients—one committee member suggested that patients would be trading one disease (FCS) for another (thrombocytopenia)—the agency also seemed to have concerns that the use of a surrogate endpoint may not have provided convincing enough evidence of efficacy to offset the safety concerns.
After the FDA’s review of the application began, Akcea submitted an unexpected amendment in which it proposed a new dosing and platelet monitoring strategy for labeling that had not been implemented in any of the clinical trials. This involved recommendations that dosing vary by body weight and that platelet monitoring occur at least every other week (more frequently if platelets fall below a certain level). “FDA reviewers questioned the feasibility and effectiveness of a monitoring scheme of this intensity for a lifelong therapy,” a briefing document said.
In the absence of therapeutic options, patients are required to adhere to a strict diet that provides limited benefit.
“It comes up a lot – just eat a healthy diet, a low-fat diet. Diet alone is not an answer to this disease. It’s not going to prevent pancreatitis,” said Lindsey Sutton, co-founder and co-president of the FCS Foundation, and an FCS patient. “It is not going to prevent elevated triglycerides. We need a medication. We need a treatment.”
The patient group is finding hope in recent reversals the agency has made on its willingness to approve certain drugs. It is hoping to sit down with regulators soon to make its case, but it has not yet received a response from the agency to its request.
September 7, 2018
Photo: Lindsey Sutton and Melissa Goetz, co-founders of the FCS Foundation