Following the Food and Drug Administration (FDA) approval of Onpattro, Alnylam Pharmaceuticals' (ALNY 5.27%) first drug to treat hereditary transthyretin-mediated amyloidosis (hATTR), the biotech held a conference call to go over the plan for launch. Here are three things management wants investors to know:

1. The approved label

"While the indication for the U.S. label is for patients with polyneuropathy and the label does not include cardiac data, we do look forward to working with the FDA to expand the Onpattro label more broadly in the future."

-- CEO John Maraganore 

The cause of hATTR is an aggregation of the TTR protein, which mainly gets deposited in the neurological system and/or in the heart, leading to polyneuropathy, cardiomyopathy, or both. While it can affect older patients with the normal protein, hATTR is caused by an inherited mutation in the gene that promotes the aggregation.

The hope was that Onpattro could be approved for all patients with hATTR, but the FDA balked at the idea and limited it to those with polyneuropathy. The agency's decision isn't too surprising because the Apollo study that the marketing application was based on measured patients' neuropathy impairment as the primary endpoint.

The clinical trial did measure some aspects of cardiomyopathy, showing Onpattro could improve cardiac structure and function in patients with cardiac involvement. But the endpoints were defined as "exploratory," so the FDA wasn't willing to put the data on the label.

The distinction is important because Alnylam has impending competition from Ionis Pharmaceuticals (IONS 2.50%) and Pfizer (PFE). Tegsedi, which is being developed by Ionis and its marketing partner Akcea Therapeutics (AKCA), is up for review with the FDA as a treatment for polyneuropathy, but it doesn't have heart data. Pfizer recently posted solid phase 3 data for its drug tafamidis in patients with cardiomyopathy.

Doctor with her hand on a patient's shoulder

Image source: Getty Images.

2. The market size

"It's estimated that there are approximately 20,000 to 30,000 patients worldwide living with hereditary ATTR amyloidosis with polyneuropathy. Unfortunately, many of the patients suffering from this disease have yet to be diagnosed."

-- Pushkal Garg, Alnylam chief medical officer

"Many" is kind of an understatement. Alnylam estimates there are about 10,000 to 15,000 patients in the U.S., but fewer than 3,000 have been identified. To really grow Onpattro sales, Alnylam needs to start identifying undiagnosed patients. Before the launch, it started Alnylam Act, a third-party screening program, which has screened more than 6,700 samples to find more than 460 patients with pathogenic TTR mutations.

If history is an indication, Alnlyam should see the rate of screening increase now that Onpattro is approved. As other orphan diseases have seen, the number of identified patients can jump dramatically after the first drug for a disease is approved, because doctors have incentive to test since there's something to treat the patients with.

3. The price

"The average effective net price for Onpattro is projected to be $345,000 annually, taking into account mandatory government discounts."

-- Barry Greene, Alnylam's president

The average list price (which no one actually pays) is $450,000, although it'll vary from patient to patient because the drug is dosed by weight up to a certain point.

Alnylam justified the price based on the clear benefit to patients for a disease with an unmet need and a small patient population. Management also noted that this was the first RNAi medicine approved, although I'm not sure how convincing that is as a reason that the cost should be so high.

Based on the effective price, Alnylam needs about 2,900 patients in the U.S. to be a blockbuster, which seems possible based on a combination of competing with Ionis and Akcea, and a growing market if the companies can find additional patients.