AMG 747 (Tilapertin)
glutamatergic · glycine transporter 1 inhibition class / glutamatergicdata + articles · 1 listed
one study on filespec sheet4 rows
AMG 747 (Tilapertin) AMG 747, later given the generic name tilapertin, was Amgen's oral GlyT1 inhibitor entry in the crowded mid-2010s field chasing glycine-mediated NMDA enhancement for schizophrenia's negative symptoms, the same mechanistic lane as bitopertin and Org 25935. Two Phase II trials were run as an add-on to standard antipsychotics in patients with persistent negative symptoms. Pooled results at 12 weeks showed no separation from placebo on the negative-symptom rating scale used. The program's ending was abrupt rather than gradual: one participant on the 40 mg dose developed Stevens-Johnson syndrome/toxic epidermal necrolysis, a rare but life-threatening skin reaction, which triggered early termination of the studies on safety grounds before efficacy conclusions could even be fully drawn out.
- tested a mechanistically coherent glycine/NMDA enhancement strategy
- generated pooled trial data that clarified GlyT1 inhibition's limits for negative symptoms
- did not show the extrapyramidal side effects typical of dopamine-blocking antipsychotics
- one case of Stevens-Johnson syndrome/toxic epidermal necrolysis at the 40 mg dose, a serious and potentially life-threatening skin reaction
- AMG 747 was later given the official generic name tilapertin even though it never reached the market, a naming step usually reserved for drugs further along in development.
Mechanism
Selective glycine transporter 1 (GlyT1) inhibitor; same target class and rationale as bitopertin and Org 25935, aimed at boosting glycine to signaling.
Safetyrisks and cautions, not medical advice
One case ended everything. A participant taking 40 mg developed Stevens-Johnson syndrome with toxic epidermal necrolysis, a reaction that strips the outer layer of skin and the mucous membranes and can kill, and Amgen halted both studies on the spot with 232 people enrolled and only 153 having completed twelve weeks. Everything else in the pooled dataset was unremarkable: adverse event rates were similar across the 5 mg, 15 mg, 40 mg and placebo groups, with no clear differences. A single serious event in a small program cannot establish a rate, which is precisely why the program could not go on.
History
Developed by Amgen; two Phase II add-on trials in schizophrenia patients with persistent negative symptoms were terminated early after a case of Stevens-Johnson syndrome/toxic epidermal necrolysis at the 40 mg dose; pooled data published in 2017 showed no benefit over placebo.
Subjective profileweighing the evidence above
A GlyT1 inhibitor that failed on both efficacy and safety grounds, ending its development faster and less gracefully than its rivals.
Resources
This entry is here for reference.
Research
1 listed here; entry last updated July 2026
Reviews
My notesprivate to this device
FAQ
Why was AMG 747 stopped so abruptly?
A trial participant on the 40 mg dose developed Stevens-Johnson syndrome/toxic epidermal necrolysis, a severe skin reaction, which led Amgen to terminate the studies early on safety grounds.
Did AMG 747 at least show a cognitive or negative-symptom benefit before it was stopped?
No. The pooled 12-week data that was collected showed no significant difference from placebo on the negative-symptom scale used in the trials.
Limitations of the evidence
- no significant improvement on negative symptoms versus placebo
- trials terminated early, leaving efficacy data incomplete
Adverse effects
- one case of Stevens-Johnson syndrome/toxic epidermal necrolysis at the 40 mg dose, a serious and potentially life-threatening skin reaction