Orphan drugs leveraging new tech promise to cure disease
The FDA awarded breakthrough status and orphan drug designation for both patisiran and Lenti-D.
Though the drugs work differently, both leverage new technologies to deliver one-and-done treatments for patients with few other options available.
In Alnylam's case, the company is taking advantage of a biological process in which RNA molecules are used to silence the disease-causing mutation.
Meanwhile, Lenti-D is a therapy that involves harvesting the patient's own bone marrow cells, editing the faulty gene, and reinfusing modified cells back into the patient.
These niche therapies are not only drumming up attention because of their novel mechanisms of action, they're also prompting speculation about how much they'll ultimately cost.
Alnylam and Bluebird are sure to be watching the ongoing pricing debate closely, but it remains to be seen whether they'll shoot high or aim low when setting the wholesale price. For one, Alnylam says it's contemplating a pay-for-performance program in which it will consider refunds for patients in whom its drug doesn't work as expected.
The company is also offering a genetic counseling and testing program called Alnylam Act, which identifies mutations associated with ATTR amyloidosis. The counseling service is free of charge for patients living in the U.S., and the genetic testing is free for those in the U.S. and Canada.
Pricing aside, rare disease patients and their physicians are likely to be clamoring for options, placing the onus on companies to effectively communicate their data package.
For both companies, an effective messaging strategy will be to champion strong efficacy data while simultaneously reassuring physicians these therapies are unlikely to cause irreparable harm.
To that end, Alnylam and Bluebird Bio are likely to deploy medical liaisons to assure clinicians these new drugs are not only effective cures, but also have a tolerable safety profile.
The drug is poised for FDA approval on August 11 after promising Phase III data demonstrated patients' improvements in motor function, neuropathy, and other disease symptoms. The placebo-controlled trial also showed a favorable safety profile. The FDA is not planning to convene an advisory committee meeting to review Alnylam's application materials.
“[Patisiran] appears to have a decent magnitude of effect in both the neurological and cardiac manifestations” of the disease, explains Dr. Leon Henderson-MacLennan, medical adviser for inThought Research.
“I and a lot of my colleagues like it because it is influencing the underlying biology of the condition.” Another messaging plus: A post-hoc analysis of the Phase III placebo-controlled trial found the drug reduced hospitalizations and deaths by 50%.
Baglin notes Alnylam execs are sensitive to ongoing price-gouging conversations and currently talking with payers about risk-sharing agreements.
“Payers will take comfort in post-hoc analyses that demonstrate a 50% reduction in all cause hospitalization and mortality,” says Madhuri Fletcher, Ph.D., SVP, medical director, Heartbeat.
“When you have a completely new drug such as this, the first thing to do is seed the market, which they've been doing already,” says Richard Meyer, principal at Strategic Marketing Solutions.
Explains Baglin, “We're talking a few thousand patients at most in the U.S., so it wouldn't make sense to go with a big direct-to-consumer TV approach.”
“There are people waiting in the wings for this,” notes Henderson-MacLennan. And for those who haven't yet been diagnosed, such as the family members of patients, Alnylam is rolling out a free diagnostic program.
According to Meyer, the pay-for-performance model paired with the free diagnostic would create a scenario in which physicians have “nothing to lose.”
In a press release, Bluebird's chief medical officer, David Davidson, M.D., said the company believes Lenti-D will “keep these boys alive and free from major functional disabilities while avoiding many of the safety risks of the current standard of care.”
“There's always a question with these novel medicines of ‘how do we measure effect?'” Henderson-MacLennan says, pointing out only two of the 17 patients evaluated were found to be living with detrimental quality-of-life indicators such as tube feeding, incontinence, loss of voluntary movement, and other disabilities associated with CALD.
“That bodes well because these are parts of the natural history of the condition that would otherwise not be influenced,” he notes.
The authors of the NEJM study are “icons in their field, [and] that bodes well also as it comes onto the market,” notes Henderson-MacLennan. Eventually, he predicts we'll see newborn screening for CALD because of the current paradigm of catching orphan diseases in childhood.
According to Beins, “We suspect Bluebird will benefit from indexing heavily on disease state education to prepare physicians and families to identify ALD early, combined with policy efforts to make ALD genetic testing a standard newborn screen.” Adds Meyer, “The only potential downside is if it's priced really high and they don't do a pay-for-performance” pricing strategy.