Welcome to your weekly digest of approaching regulatory and clinical readouts. Tiny Axsome is expecting two key readouts of its depression pill AXS-05 as 2018 ends and 2019 begins. A phase II trial in major depressive disorder and a phase III in treatment resistant depression are both expected to yield data.
AXS-05 combines bupropion, the active ingredient in Wellbutrin, with dextromethorphan, an NMDA antagonist more often known as an expectorant. Axsome’s case for the combination centres on bupropion’s ability to slow metabolism of the dextromethorphan to achieve the plasma concentrations necessary for psychotherapeutic effects.
Data from the phase II Ascend trial in major depressive disorder is expected in early January following completion of enrolment in November. The phase III Stride-1 trial in treatment resistant depression will follow suit sometime in the first quarter.
The timeline for Stride-1 accelerated from mid-2019 after Axsome decided against conducting a second interim analysis in order to preserve statistical power for a final analysis at 250 patients. AXS-05 passed a test for futility in April 2018, and 80% of the patients necessary for a final analysis had been recruited as of early November.
Both trials compare AXS-05 against single-agent bupropion, with Stride-1 using the Montgomery-Åsberg depression rating scale (MADRS) at six weeks as a primary endpoint. MADRS at six weeks is one of the endpoints being used in Ascend, although this is primarily a safety study.
Success with either of these two trials could open the door to dealmaking talks. Axsome will likely need a bigger partner to launch a mental health drug.
AXS-05 has another shot on goal in the shape of a trial in Alzheimer’s disease agitation. That phase II/III study is expected to be subject to an interim analysis by the end of 2018.
|Stride-1||Phase III in treatment resistant depression||
|Ascend||Phase II in major depressive disorder||NCT03595579|
The rest of the world might be counting down to Christmas, but investors in Aldeyra Therapeutics will have to wait until the New Year for their next big event: phase III results for eye treatment reproxalap (ADX-102) in allergic conjunctivitis. The trial is just one of four pivotal catalysts for the compound in the coming 12 months and investors will be hoping that these will prompt share price rises similar to the one Aldeyra enjoyed in September following a positive phase II result in dry eye disease.
As analysts are forecasting allergic conjunctivitis to be the second biggest indication for reproxalap, if the data are positive the stock reaction could be significant. However, the group’s past track record in allergic conjunctivitis has been less than solid.
|Reproxalap sales by indication|
|Indication||2024 sales ($m)||Phase|
|Dry eye||343||Phase II|
|Allergic conjunctivitis||185||Phase III|
In a 2017 phase IIb trial reproxalap failed to meet the primary endpoint of showing a one-point improvement over placebo on a scale of eye itching. Some might see designing the Alleviate phase III trial along similar lines to the phase IIb as a risky move. In the 300 patient study, 0.25% and 0.5% solutions of reproxalap will be tested against a placebo vehicle. The primary endpoint remains reductions in patient-reported itching.
After allergic conjunctivitis, the next event for reproxalap is Sjögren-Larsson Syndrome followed by non-infectious anterior uveitis. Hopes have been raised in dry eye not only due to the positive readout from the phase IIb trial, but because of reproxalap’s relatively fast onset of action, compared with the currently approved Restasis and Xiidra. Restasis in particular can take take months to demonstrate efficacy.
|Phase III clincal trials for reproxalap|
|Early 2019||Alleviate trial - allergic conjunctivitis|
|H2 2019||Reset trial - Sjögren-Larsson syndrome|
|H2 2020||Solace trial - non-infectious anterior uveitis|
|2019||Start of phase III trial in dry eye disorder|
One of the big questions for Aldeyra is whether it will take reproxalap to market in its various indications on its own, or find a bigger partner. A $68m fundraising in October has given the group a cash runway until 2020, enough time to complete the phase III trial. The group will either be banking on good data throughout the year to hang on the back of another more substantial fundraising or find a partner to commercialise the drug.