FDA OKs Akcea Rare Disease Drug, Setting Up Market Clash with Alnylam

Xconomy Boston — 

For the second time since August, the FDA has approved a new treatment for a rare and deadly disease called hereditary transthyretin amyloidosis (hATTR). The agency’s nod for inotersen (Tegsedi) sets the stage for a market battle between the drug’s developer, Akcea Therapeutics, and rival Alnylam Pharmaceuticals.

The FDA approved inotersen for treating polyneuropathy, the peripheral nerve damage suffered by hATTR patients. The approval comes with a black box warning on the drug’s label that cites the risk of inflammation of the kidneys, a complication that can be triggered by an immune response to the drug. Consequently, the FDA is requiring frequent monitoring of patients treated with the Akcea (NASDAQ: AKCA) drug. The company must also draw up a strategy to evaluate and mitigate the risks associated with the drug. Speaking on a conference call with analysts Friday evening, Akcea CEO Paula Soteropoulos said the stringent FDA warning was not a surprise.

“We expected it and we are very much ready to support patients,” she said.

Cambridge, MA-based Akcea set a $450,000 annual price for inotersen, matching the price of Alnylam’s patisiran. Soteropoulos said Akcea is considering various strategies, including value-based pricing, to ensure access and affordability of the drug. The company is working with Accredo, a specialty pharmacy and Express Scripts (NASDAQ: ESRX) subsidiary, to provide the drug. Akcea expects the drug will become available to U.S. patients “in coming months.”

The average list price of Alnylam’s patisiran doesn’t include rebates to insurers. Taking into account rebates, the average net price is $345,000 per year, Alnylam has said. But the company has also launched patisiran with deals in place with payers to tie patisiran’s price to its performance. It hasn’t disclosed the specifics of those deals, but executives have said that Alnylam would be paid in full if a patient improves, and would provide discounts if the disease gets worse. Soteropoulos said Akcea is still discussing reimbursement strategies with insurers.

The rare disease hATTR affects an estimated 50,000 people worldwide. People who have the disease make a mutated version of the protein transthyretin (TTR), which builds up in misfolded clumps, causing damage to a variety of tissues around the body. Some patients suffer just the nerve damage, which starts with numbness in the toes, then feet, and moves upwards. Others suffer a corrosion of the heart’s wiring that can lead to heart failure and death. Most patients have elements of both issues.

For years, the only treatments in the U.S. were liver transplants or diflunisal, a generic anti-inflammatory drug used off-label to “stabilize” the TTR protein and slow the progressive nerve damage. But liver transplants are risky, tough to get, and don’t always work. And diflunisal can cause stomach or kidney problems, so it isn’t for everyone.

The treatment paradigm for hATTR is now changing. With the arrival in August, first, of patisiran, and now inotersen, two new drugs have emerged that could give patients the chance to halt the progression of their nerve damage—and in some cases, improve nerve function. European regulators approved inotersen in July and patisiran in August. Inotersen was also approved in Canada earlier this week.

Also in the mix is tafamidis (Vyndaqel), a Pfizer drug that is similar to diflunisal and is approved in Europe but not in the U.S. Pfizer (NYSE: PFE) could soon file for approval of its drug for hATTR patients with heart problems, and whether the FDA ultimately approves tafamidis—it rejected the drug several years ago—could affect the commercial potential of both patisiran and inotersen.

In the meantime, however, Akcea and Alnylam will duke it out for market share. The biggest differences between the two drugs is how they are administered, and their side effects. Alnylam’s drug is given via infusion at a clinic once every three weeks and patients are given precautionary analgesics and corticosteroids before each dose. Inotersen is a once-weekly self-administered subcutaneous injection. Alnylam has touted patisiran’s safety profile, while worrisome kidney problems and dangerously low platelet counts have cropped up in clinical studies of inotersen—which is why patients will require frequent monitoring.

The decision is welcome news for Akcea, meanwhile. The company, spun out of Ionis Pharmaceuticals (NASDAQ: IONS), to commercialize drugs developed by Carlsbad, CA-based Ionis, axed 10 percent of its workforce last month after the FDA rejected volanesorsen (Waylivra), for the ultra-rare disease familial chylomicronemia syndrome. Volanesorsen was the only other Akcea drug close to regulatory approval. A third experimental treatment, for heart disease, is in mid-stage testing.

Frank Vinluan contributed to this report.

Photo by Akcea Therapeutics