Epilepsy Treatment In Limbo As Addex’s Partner Abandons ADX71149
Janssen stops ADX71149 development for epilepsy; Addex and Janssen still analyzing Phase 2 data.
Breaking News
Jul 22, 2024
Mrudula Kulkarni

Addex Therapeutics, a clinical-stage biopharmaceutical
company dedicated to developing innovative small molecule allosteric modulators
for neurological disorders, has announced that Janssen Pharmaceuticals, Inc.
(now J&J Innovative Medicine) has decided to halt the development of
ADX71149 (JNJ-40411813) for epilepsy. Despite this, the collaboration between
the two companies will continue as they analyze the complete data set from the
Phase 2 study of ADX71149 as an adjunctive treatment for epilepsy.
This decision comes after the release of top-line Phase 2
data on April 29, 2024. The data revealed that the adjunctive administration of
ADX71149 in patients with focal onset seizures, who had an inadequate response
to levetiracetam or brivaracetam, did not reach statistical significance for
the primary endpoint. This endpoint was the time it took for patients to return
to their baseline seizure count when ADX71149 was added to their standard care
regimen.
ADX71149 is a targeted positive allosteric modulator (PAM)
of the selective metabotropic glutamate subtype 2 (mGlu2) receptor. The
multi-center Phase 2 trial aimed to evaluate the efficacy, safety,
tolerability, and pharmacokinetics of ADX71149 as an adjunct therapy in
patients with focal onset seizures who had an inadequate response to
levetiracetam or brivaracetam. The main goal was to determine the effectiveness
of ADX71149 when used alongside levetiracetam or brivaracetam by measuring the
time it took for patients to return to their baseline seizure count.
The study had two parts: Part 1 assessed the short-term
effectiveness of ADX71149 over four weeks. Patients who did not reach their
monthly baseline seizure count during this period continued in the double-blind
treatment phase (Part 2), which lasted until they either reached their monthly
baseline seizure count or completed eight weeks, known as the maintenance
efficacy phase. Detailed information about the study is available under
Clinicaltrials.gov identifier NCT04836559.
Glutamate is the brain's main excitatory neurotransmitter,
playing a crucial role in the onset and spread of seizures. Activation of the
mGlu2 receptor reduces glutamate release, helping to balance neurotransmitter
levels. Positive allosteric modulation of mGlu2 receptors, when triggered by
agonists, can normalize the excessive glutamate release observed during
seizures. Epilepsy remains a significant unmet medical need, with many patients
facing challenges in managing their seizures daily.
Through their research collaboration and license agreement,
Addex has provided Janssen Pharmaceuticals, Inc. with an exclusive global
license to develop and commercialize mGlu2 PAM compounds. Addex stands to
receive up to €109 million in success-based development and regulatory
milestone payments. Additionally, Addex is eligible for low double-digit
royalties on net sales of compounds developed under this agreement.