Just over a year after being spun out of Astrazeneca, Viela Bio is moving closer to getting its first approval, for the neuromyelitis optica project inebilizumab. There is just one problem: Alexion’s rare disease juggernaut Soliris has got there first.
The American Academy of Neurology meeting this week featured positive data on both projects, along with results on another candidate, Roche and Chugai’s satralizumab. Viela might have a hard time going up against rivals of this size, particularly with Soliris set to reach the market first.
Viela executives are undaunted, telling Vantage that several factors could give inebilizumab an edge over Soliris in neuromyelitis optica spectrum disorder (NMOSD), an autoimmune condition that causes swelling of the optic nerve and spinal cord, and can lead to blindness or paralysis. One of the main causes is thought to be aquaporin 4 antibodies, which are found in around 80% of NMOSD patients.
There are no approved therapies for NMOSD, but patients often receive off-label immunosuppressants or steroids.
In Soliris's pivotal study Alexion allowed patients to continue taking any immunosuppressive medication, while Viela tested inebilizumab monotherapy. This could avoid what Viela’s chief medical officer, Jorn Drappa, called “the confounding influence of other medicines”.
N-Momentum included aquaporin 4-positive and negative subjects, but the latter only made up around 9% of the 230-patient trial, and the primary endpoint analysis was in antibody-positive patients only.
In this population inebilizumab reduced in the risk of an NMOSD attack by 77%. Across all 230 patients there was a 73% reduction in the risk of attack with inebilizumab.
Still, the Soliris results look more impressive. Alexion released topline data from the Prevent trial in September, and presented more detailed results at AAN on Tuesday.
|Neuromyelitis optica: the data so far|
|Project||Company||Study||Setting||AQP4 positive/ negative?||Reduction in attack risk||2024e NMO sales ($m)|
|Soliris||Alexion||Prevent, NCT01892345||Mainly add-on||Positive||94%||319|
|Inebilizumab||Viela Bio||N-Momentum, NCT02200770||Monotherapy||Both||73%||-|
|SakuraStar, NCT02073279||Monotherapy||Positive||Met primary endpoint|
|AQP4: Aquaporin 4 antibody; Source: Company releases, EvaluatePharma.|
In addition to the usual caveats about cross-trial comparisons, several differences between the studies make this even trickier than normal.
Around 75% of patients in Prevent were receiving background immunosuppressants, although Alexion’s global head of R&D, John Orloff, told Vantage that the efficacy of Soliris monotherapy was just as good.
He pointed to a relapse-free rate at 144 weeks of 95% in the add-on group and 100% for monotherapy, but conceded that the number of patients given Soliris alone was small.
In addition, Viela focused on a slightly less severe patient population at baseline: to enrol into N-Momentum, patients had to have experienced one attack in the past year, or two in the past two years, whereas Prevent included patients who had had two attacks in the past year, or three in the past two.
According to Viela's Mr Drappa, the N-Momentum population was more representative of patients with NMOSD.
Inebilizumab, which is given via a 90-minute intravenous infusion every six months, could also be more convenient that Soliris, which is administered intravenously every two weeks.
Alexion’s Mr Orloff does not believe that this will be an issue in a disease as serious as NMOSD. “Our efficacy is unmatched. If [taking another drug] means one extra relapse for patients because they don’t achieve the efficacy we have, that could be their last relapse.”
Later this year Alexion plans to start a trial of its Soliris follow-on, Ultomiris, in NMOSD. This is administered every eight weeks, so would be more convenient than Soliris.
A wildcard could be Roche and Chugai’s satralizumab, which is given subcutaneously once a month. The data so far, from the SakuraSky trial testing it as add-on therapy, have fallen short of those seen with Soliris and inebilizumab, with a reduction in attack risk of 62% across antibody-positive and negative patients. Homing in on aquaporin 4-positive patients gave a more impressive 79% reduction in the risk of attacks.
All eyes will now be on the SakuraStar trial of satralizumab monotherapy; so far, the companies have only said that this met its primary endpoint.
These NMOSD contenders all work differently: Soliris inhibits complement C5, satralizumab is an antibody against IL-6, and inebilizumab is an anti-CD19 antibody designed to deplete B cells.
Rituximab, an anti-CD20 MAb that is also used off-label in NMOSD, has a similar action to inebilizumab, but Viela's Mr Drappa says that the B cells that make the pathogenic aquaporin 4 antibody are negative for CD20.
Viela believes that the strength of its data in a broad patient population, plus the convenience advantage, will help it compete. It hopes to file its project with regulators in mid-2019.
But Soliris is due a US approval decision in NMOSD by June 28, and Alexion, which has dominated other rare diseases, will make its first-move advantage count. With only around 10,000 NMOSD patients in the US, Viela could struggle to catch up.