Welcome to your weekly roundup of approaching clinical readouts. Axsome is due to report data by the end of the year with AXS-07 in acute migraine patients who have had an inadequate response to prior acute treatments.
Acute migraine therapy is dominated by generic triptans; AXS-07, a combination of rizatriptan and the Cox-2 NSAID meloxicam, is essentially designed to be a better version of these older drugs. This means that Axsome is aiming for a different slice of the market than oral CGRP inhibitors, for example, which will likely be reserved for patients who do not respond to triptans or cannot take them – the drugs are linked with cardiovascular side effects.
AXS-07 uses Axsome’s MoSEIC technology, which is designed to improve drug absorption. Leerink analysts say the project could find a niche as a faster-onset version of its established components, which could help AXS-07 gain market share in the front-line setting – if its price is not a hindrance. But AXS-07 might end up with a cardiovascular warning on its label, like other triptans.
First, the project will need a win in the phase III Momentum trial. The 875-patient study is testing AXS-07 versus rizatriptan and meloxicam alone, or placebo. The co-primary endpoints are freedom from headache pain and freedom from the most bothersome migraine-associated symptom two hours after dosing, for AXS-07 compared with placebo.
Superiority of AXS-07 to the rizatriptan and meloxicam arms could be established based on sustained freedom from headache pain from two to 24 hours after dosing, and a look at historical data with rizatriptan shows what Axsome's project might need to achieve.
|What AXS-07 needs to beat: rizatriptan results|
|% of patients reporting complete pain relief at 2hr, placebo-adjusted (NCT00897949)|
|Maxalt* 5mg||Maxalt 10mg|
|*Branded rizatriptan (Merck & Co). Source: publication.|
Axsome recently started another acute migraine trial of AXS-07, called Intercept, which is due to read out in the first quarter of 2020. This will evaluate treatment with AXS-07 as soon as a migraine starts, rather than waiting for the migraine to reach moderate to severe intensity, which is typical in migraine trials.
However, according to Axsome, Momentum will be the only study required for the NDA filing, which is expected in the second half of next year.
|Top migraine products in 2024, excluding anti-CGRPs|
|Annual indication sales ($m)|
|Qtrypta*||Zosano Pharma||-||111||Phase III|
|AXS-07*||Axsome Therapeutics||-||50||Phase III|
|XEN007||Xenon Pharmaceuticals||-||33||Phase I|
|*Contain triptan. Source: EvaluatePharma.|
Back in its Stride?
Meanwhile, after being hit by a complete response letter in August, Kala’s KPI-121 needs to shine in its next phase III trial, Stride 3, with data expected in the first quarter of 2020.
The regulatory knockback was not hugely unexpected as the dry eye project, which Kala has branded Eysuvis, produced mixed results in two previous trials, with Stride 2 missing one of its co-primary endpoints, ocular discomfort. This is the sole primary endpoint of Stride 3, which will compare KPI-121 0.25% with placebo. Each cohort will be dosed four times a day for two weeks in approximately 900 patients with dry eye disease.
Kala hopes that changes to the inclusion/exclusion criteria could give Stride 3 a better chance of success – the company previously said that patients in Stride 2 had variable levels of symptoms at baseline.
If Stride 3 hits a resubmission could occur in the first half of next year, followed by a six-month review, according to the company. The next challenge would be hitting sellside numbers: 2024 sales are forecast to reach $710m, and the project has an NPV of $1.5bn, according to EvaluatePharma consensus, making it Kala’s most valuable project asset.
However, the company's market cap is just $126m, so investors apparently do not share the sellside's enthusiasm.
|KPI-121 phase III data|
|Results of primary endpoints, baseline to day 15, ITT population|
|Study||Sign endpoint (conjunctival hyperaemia)||Symptom endpoint (ocular discomfort severity)||Trial ID|
|Stride 1||Met p<0.0001||Met p<0.0001||NCT02813265|
|Stride 2||Met p<0.0001||Missed p=0.1298||NCT02819284|
|Stride 3||-||Data due by year end||NCT03616899|
|Source: company press release.|