Alnylam Pharmaceuticals already sells an infused treatment for the nerve damage caused by a rare, inherited disorder, one of the company’s three commercialized RNA interference (RNAi) drugs. The company is laying the groundwork to potentially bring a fourth such drug to the market.
Cambridge, Massachusetts-based Alnylam has applied for FDA approval of vutrisiran. Like its first FDA-approved medicine, patisiran (Onpattro), the drug is an RNAi therapy for the nerve damage caused by hereditary transthyretin amyloidosis (hATTR). But unlike Onpattro, which is administered as an infusion every three weeks, vutrisiran is an injection given once every three months, which Alnylam executives say could open the door to treating more patients who have the rare disease.
“Worldwide speaking, less than 30 percent of [hATTR] patients are diagnosed,” said Chief Commercial Officer Tolga Tanguler, speaking on an April 19 conference call. “A lot fewer of those patients are currently being treated. That’s where the opportunity is going to be. If and when vutrisiran is approved for polyneuropathy, given the treatment regimen of once quarterly infrequent dosing, without any safety monitoring, is going to be a real, real benefit for the patient.”
Patients who have hATTR produce a misfolded version of a protein called transthyretin (TTR), which builds up in clumps throughout the body. This protein buildup can affect the heart, the gastrointestinal tract, and the kidneys. The disease often becomes fatal.
RNA interference therapies stop a gene from producing a disease-causing protein. In the case of hATTR, RNAi drugs are intended to stop the formation of the mutated TTR. By reducing the amount of TTR produced in the liver, Alnylam’s drug is meant to reduce the deposition of the proteins that cause the effects of hATTR, potentially stopping or even reversing disease progression.
Submission of vutrisiran for FDA review comes after Alnylam presented full results from a Phase 3 study at the annual meeting of the American Academy of Neurology last week. After nine months of treatment, the study met the main goal of showing improvement from baseline according to a scale that measures neuropathy impairment. Those results were compared to the placebo data from the pivotal study evaluating Onpattro. According to Alnylam, the majority of patients showed improvement in neuropathy and in quality of life. Vutrisiran also met safety benchmarks. No patients dropped out of the clinical trial due to problems with the drug and no deaths were reported in the study.
In addition to the main goal, the clinical trial also included the exploratory goal of evaluating what the drug did for the heart. Alnylam reported that according to a measure of cardiac stress, improvement was observed in patients treated with the study drug compared to an external placebo group.
Besides seeking FDA approval of vutrisiran, Alnylam is planning to file regulatory submissions in Brazil, Japan, and Europe. The company aims to add vutrisiran to its growing portfolio of RNAi therapies. Onpattro was approved in 2018, the first drug in this class to pass the regulatory bar. In 2020, the drug accounted for $306 million in revenue, a nearly 84% increase over the prior year, according to Alnylam’s annual report.
In 2019, the FDA approved givosiran, marketed as Givlaari, for treating acute hepatic porphyria. Last year, the agency approved lumasiran, marketed as Oxlumo, an RNAi drug for primary hyperoxaluria type 1.
Vutrisiran’s progress comes as Alnylam responds to a federal subpoena about Onpattro. On April 12, the company disclosed in a regulatory filing that the Department of Justice is requiring the company to produce documents relating to the company’s marketing and promotion of the drug in the U.S. Speaking on the conference call, CEO John Maraganore acknowledged Alnylam received the subpoena, and he said the company is cooperating. But he did not elaborate beyond what the regulatory filing stated.
“We always feel very strongly about the importance of ethics and compliance and integrity in everything that we do, but obviously we’ll work with the government to answer their questions,” he said.
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