Orphan drugs leveraging new tech promise to cure disease

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In an era of unprecedented drug approvals for rare diseases, two late-stage drugs are upping the ante with their promise to cure disease rather than treat symptoms. First to market will be Alnylam's patisiran for ATTR amyloidosis, followed by Bluebird Bio's Lenti-D for cerebral adrenoleukodystrophy (CALD).

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.

Patisiran
Alnylam/Sanofi, preregistration
Indication: ATTR amyloidosis

Catalyst: Patisiran is an RNAi therapeutic designed to treat hereditary ATTR amyloidosis, a disease caused by a genetic mutation that leads to protein buildup and subsequent tissue damage. “Because this is a hereditary disease with multiple generations fighting together, support communities will also be key, creating opportunities for Alnylam to partner with families, patient advocates, physicians, and KOLs to advance the promise of the treatment,” says Simon Beins, VP, strategy, Heartbeat.

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.

Competitive landscape: Due to a lack of other good treatment options, patisiran is slated to become the standard of care for hereditary transthyretin-mediated amyloidosis, according to analytics firm Clarivate. Worldwide, the patient population is tiny, with fewer than 50,000 patients thought to suffer from this disease. Right now, the only other treatment option is liver transplant — a risky, last-resort operation that reduces the amount of ATTR protein made in the body. In Europe, there is one drug approved called tafamidis, which merely slows down the progression of the disease rather than reversing it, as patisiran appears to.

Messaging strategy: For Alnylam's VP of global marketing Mark Baglin, the messaging strategy around patisiran will focus on its novelty, value, and quality of life impact. “This will be the first FDA-approved RNA interference therapy,” he notes. “It's a huge breakthrough.”

“[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.

Marketing strategy: With the FDA's approval decision imminent, Alnylam is gearing up its marketing strategy. The company's AOR is Dudnyk, and it will work with Evolution Medical Communications for its medical comms strategy. In the meantime, medical marketing agency Snow Companies is leading ongoing patient ambassador efforts, and will lead brand ambassador efforts post-approval. 

“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.”

Lenti-D 
bluebird bio, Phase III
Indication: Childhood cerebral adrenoleukodystrophy (CALD)

Catalyst: Lenti-D is a therapy for CALD, an X chromosome-linked genetic disease usually fatal in boys. Initial data from Bluebird Bio's Starbeam Study was published in The New England Journal of Medicine in October. In that study, 88% of patients were alive and free of major disabilities after two years. Bluebird plans to present clinical data from the study in the second half of 2018. 

Competitive landscape: CALD is a more severe form of ALD, which is thought to affect one in every 20,000 people worldwide. The only treatment is an allogeneic hematopoietic stem cell transplant, which requires patients to find a perfect donor match. In addition, if the procedure is performed too late in the progression, it can be fatal. 

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.” 

Messaging strategy: Like nearly all orphan and rare diseases, the messaging strategy will rely exclusively on the drug's data package, explains Henderson-MacLennan. So, Bluebird published compelling data in the NEJM that evaluated the drug's impact on six functional disabilities. 

“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. 

Marketing strategy: Because the CALD patient population is small, Bluebird's marketing will likely focus on targeted patient communities and physicians. To that end, the NEJM article touting Lenti-D's positive impact on quality of life was a great marketing and messaging tool for Bluebird. 

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. 

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