Akcea Expects Convenience Edge For Tegsedi, Despite Monitoring Requirements
Executive Summary
Approved two months after Alnylam’s Onpattro, Tegsedi is priced almost identically in the same hATTR indication. Ionis affiliate Akcea hopes weekly subcutaneous administration will provide convenience benefit compared to I.V. Onpattro.
Akcea Therapeutics Inc. has reached the market with Tegsedi, its RNA-interference (RNAi) therapy for hereditary transthyretin-mediated amyloidosis (hATTR) related polyneuropathy, just a couple months after Alnylam Pharmaceuticals Inc. received US FDA approval for its similar drug Onpattro for the same indication. The similarities will extend to pricing, as Akcea announced it will price Tegsedi roughly on par with Onpattro.
Tegsedi (inotersen) cleared the US FDA Oct. 5 for hATTR polyneuropathy, after Alnylam’s Onpattro (patisiran) got the okay on Aug. 10 as the first drug therapy for the rare disease. (Also see "Alnylam Offers Flexible Value-Based Deals For Breakthrough RNAi Drug Onpattro" - Scrip, 11 Aug, 2018.)
Akcea, an Ionis Pharmaceuticals Inc. spinout focused on cardiometabolic RNAi therapies, announced that a single, prefilled syringe of Tegsedi will cost $8,650 wholesale, which would come to $449,800 over a full year if taken once-weekly as the label instructs. Alnylam set a wholesale acquisition cost of $450,000 annually for Onpattro, an intravenous infusion with thrice-weekly administration recommended. Tegsedi can be self-administered once the patient is certified, which Akcea views as a key convenience advantage and allows for reimbursement under pharmacy benefits rather than medical.
“One of the advantages with Tegsedi, because it’s a weekly injection [rather than intravenous], it’s on pharmacy benefit and that’s much easier for payers to administer. There’s no administration cost and there’s no wastage with it either,” Akcea President Sarah Boyce told Scrip.
Betting On Convenience Of Self-Administration
Stressing that amyloidosis patients face significant life disruption, Akcea executives are betting that their convenience of administration advantage will be welcomed by patients and physicians alike, even though Tegsedi’s label requires both doctors and patients to be certified for a pair of monitoring requirements: weekly blood draws to check platelet counts, and urine samples every other week to assess kidney function. Onpattro’s labeling does not include any monitoring requirements.
The Tegsedi US label includes a boxed warning about the risks of both thrombocytopenia and glomerulonephritis. The drug also has a Risk Evaluation and Mitigation Strategy (REMS) with restricted distribution in addition to the patient/physician certification. Akcea is partnering with Express Scripts Holding Co.’s specialty pharmacy Accredo for distribution.
Tegsedi also is approved in Europe – the first patient recently was dosed in Germany – and obtained Canadian regulatory approval on Oct. 4. (Also see " Aimovig And Tegsedi In Raft Of Products To Get EMA Thumbs up " - Pink Sheet, 1 Jun, 2018.) In both of these markets, platelet monitoring every other week is required, as was requested by Akcea in its US filing for Tegsedi. The European and Canadian approvals also require urianalysis for kidney function once every three months.
On an Oct. 5 investor call, Akcea executives explained that they anticipated monitoring requirements, after receiving a complete response letter from the FDA in August for Waylivra (volanesorsen) for familial chylomicronemia syndrome (FCS) because of safety concerns about thrombocytopenia due to reduced platelet counts. Thrombocytopenia is a concern with the RNAi platform. (Also see "Complete Response Letters See Uptick With US FDA's Thumbs Down For Waylivra " - Pink Sheet, 28 Aug, 2018.)
Akcea eventually plans to appeal to the FDA to relax the monitoring requirements in Tegsedi’s labeling. Boyce said it would use real-world evidence from commercial use in Europe and Canada, as well from the US, including the ongoing open-label extension study, for the filing.
In rolling out Tegsedi, Akcea is launching the Akcea Connect program which will provide each patient with a nurse case manager who will get the patient enrolled in platelet and kidney monitoring to be provided by Quest Diagnostics Inc. under a contract with Akcea. Patients will have the option of having a Quest phlebotomist visit them each week to draw blood, or going to one of Quest’s more than 2,200 locations in the US, Boyce explained.
The executive said Akcea already has built the cost of the Quest monitoring into its economics for Tegsedi, but declined to estimate what the annual cost of paying for the monitoring might be.
While the epidemiology of hATTR is evolving, Boyce said on the investor call that Akcea estimates there are about 3,000 diagnosed patients in the US and another 12,000 not yet diagnosed. Globally, it projects an hATTR population of about 50,000 with about 60% experiencing polyneuropathy.
The monitoring protocol Akcea has set up follows the practices used in both an open-label extension of its Phase III NEURO-TTR pivotal trial and an early access program for the drug. Considering there was no approved treatment for hATTR polyneuropathy up until a few months ago, Boyce said Akcea has gotten considerable feedback indicating that the monitoring requirements are not seen as too onerous.
“In terms of having a treatment, having to do the monitoring is no issue and we’ve ensured that it’s as simple and straightforward for patients as possible,” she said. “The types of physicians who typically deal with amyloidosis patients are used to prescribing drugs that may have a monitoring requirement or a REMS, so that’s nothing new to them either. So, in context of the benefits versus the severity of the disease, this is something that we hear people saying will be very manageable. The key thing is establishing a routine and that’s one of things we’re doing as much as we can to help with that.”
Analysts Concerned Monitoring Requirements Burdensome
While market analysts hailed the approval, they expressed skepticism that the monitoring requirements would affect Tegsedi’s ability to build market share. BMO Capital Markets analyst Do Kim asserted in an Oct. 7 note that the black box warning might deter some physicians and patients, adding that Alnylam must overcome the need to pre-medicate Onpattro patients with steroids plus a more burdensome route of administration.
“We believe Akcea’s efforts to minimize the inconvenience of weekly platelet monitoring and biweekly urinalysis should aid in adoption,” Kim wrote. “We believe sufficient preference for weekly self-injections, versus eight-hour I.V. infusions every three weeks should enable Tegsedi to capture a 25% market share.”
Laidlaw & Co. analyst Yale Jen pointed out in an Oct. 8 note that there have been few incidences of thrombocytopenia since Akcea adopted platelet monitoring in its clinical trials and predicted a modest ramp-up that will build over time for Tegsedi. “Tegsedi adoption could accelerate once patients and physicians feel more comfortable about the thrombocytopenia concern and like to take advantage of the subcutaneous self-administrated at-home delivery benefits,” he wrote. “We do not view the efficacy of the two drugs is meaningfully different in real world practice.”
Morgan Stanley’s David Lebowitz called the monitoring requirements “more burdensome than we had anticipated.” In an Oct. 8 note, he reduced his projections for Tegsedi sales in 2025 slightly, from $422m to $405m, based on the label.
Akcea and Alnylam may soon have further competition in the hATTR space, although in a separate sub-indication. Pfizer Inc. has Phase III data for oral tafamidis showing reduced all-cause mortality and cardiovascular-related hospitalization in hATTR cardiomyopathy patients. (Also see "As Gilead Seeks New CEO, Second Quarter Shows Stability" - Scrip, 25 Jul, 2018.) The company has stressed that its indication is entirely different from hATTR polyneuropathy, but analysts generally expect some off-label usage in both directions once all three drugs are on the market.