Dive Brief:
- AveXis, Inc. has gotten the go ahead from the Food and Drug Administration to kick off its pivotal trial of AVXS-101 in spinal muscular atrophy (SMA) type 1 using an intravenous formulation produced through its Good Manufacturing Practice (GMP) commercial manufacturing process. The company's cGMP facility is expected to be able to meet the company's needs for both clinical and commercial supply.
- The study, which will begin immediately, will recruit a minimum of 15 patients under six months old with SMA type 1. The infants will be given a once-only dose of the gene therapy AVXS-101, based on one of the doses from the previous Phase 1 trial. The study could readout in 2019.
- AveXis anticipates starting its study in patients with SMA type 2 in the fourth quarter 2017, following ongoing discussions with the FDA.
Dive Insight:
Earlier this year, AveXis submitted responses to the FDA following a Chemistry, Manufacturing, and Controls Type B meeting, which have all been reviewed and accepted, including confirming the equivalence of the dose used in the Phase 1 and the Phase 2/3 study.
"We are pleased to reach this outcome following a thorough review by the FDA of the voluminous information we supplied to address the commitments made during the Chemistry, Manufacturing, and Controls Type B meeting in May," said Sean Nolan, president and CEO of AveXis. "Moving AVXS-101 back into the clinic, as planned, with product from our GMP process is a significant milestone."
The co-primary endpoints of the study will be independent sitting for at least 30 seconds at 18 months of age, and event-free survival at 14 months of age.
"We think recruitment will take place quite rapidly. We have had multiple requests and we believe it could be completed within six to nine," said Sukumar Nagendran, CMO.
The FDA has not said that it will require data on the first three patients of the pivotal study, according to Nolan, but the company aims to be transparent on the data and will send it through to the FDA as soon as it is quality controlled.
"We have a date set late in the fourth quarter for the end of Phase 1 meeting. We will discuss the Phase 1 and comparability data, looking at the approvability and the approval pathways, including, potentially, accelerated approval," said Nolan. "There is no prespecified interim analysis in the protocol, but because it is open label we will have access to the data. We will have the opportunity to take the data to the FDA earlier if it is appropriate."
"Given the immediate start of this trial, we believe AveXis will have initial safety/efficacy data available for the end of Phase 1 meeting scheduled for late in the fourth quarter and could enable filing in 2018," Biren Amin, equity analyst at Jefferies, said in a note to clients.
Further discussions are under way with the FDA for the planned intrathecal study of AVXS-101 in patients with SMA type 2, as Nolan explained on a conference call with analysts
"The discussions for both programs have been highly constructive, and there were no major points of difference between what was submitted and what was requested. The FDA moved mountains to review the information. Rather than trying to manage all of the FDA requests for both studies simultaneously, because of resources, we asked the FDA to prioritize the pivotal trial. Now we are moving into the clinic, we will continue the dialog on the type 2 trial. It is difficult to predict the timelines but if all goes well, we anticipate dosing patients in the fourth quarter of 2017," he said.
Should it reach the market, AveXis' drug would be up against Spinraza (nusinersen), an injectable antisense drug from Biogen, Inc. and Ionis Pharmaceuticals, Inc. The Food and Drug Administration approved Spinraza in December 2016, five months ahead of its user fee goal date of May 26, 2017.
Spinraza picked up approval from the Food and Drug Administration in December 2016, around five months ahead of its user fee goal data of May 26, 2017. Its high price tag of $125,000 per vial and pushback from payers was expected to slow uptake, but sales have grown strongly.
Swiss pharma Roche AG and PTC Therapeutics are also looking at this market. They are developing the small molecule, oral drug RG7916 in the Phase 2 SUNFISH trial in type 2/3 SMA. AVXS-101, however, has the advantage of a once-only administration.