Lysergic acid diethylamide

Definium Therapeutics' experimental psychedelic therapy has passed another Phase III test, this time in anxiety.The biotech said DT120, its orally disintegrating tablet formulation of lysergide (LSD), met the primary and all key secondary endpoints in the Voyage study of adults with generalised anxiety disorder (GAD), giving the company its second positive Phase III readout in less than two months.The result follows DT120's June success from the Emerge study in major depressive disorder (MDD).As he had when those results were announced, CEO Rob Barrow called Wednesday's topline data from Voyage "unprecedented," adding they "should raise the bar for what patients and clinicians expect from GAD treatments and reinforces our belief that DT120 has the potential to redefine care for the millions of patients."Voyage enrolled 214 adult participants who were randomly assigned either a single 100-µg dose of DT120 ODT or placebo. The study includes a 12-week double-blind period (Part A) followed by a 40-week open-label extension (Part B) in which patients may receive up to four additional doses based on symptom severity.Rapid effect after single doseAt week 12, participants on DT120 achieved a reduction from baseline of 11.6 points in Hamilton Anxiety Rating Scale (HAM-A) scores, compared to 6.2 points for placebo. The resulting placebo-adjusted difference was 5.4 points (p<0.0001), corresponding to a Cohen's d effect size of 0.81.Definium said improvements emerged as early as the second day and were sustained at all post-baseline timepoints.DT120 also significantly outperformed placebo on key secondary endpoints, including HAM-A change at week 1 and Clinical Global Impression-Severity (CGI-S) scores at day 2 and week 12. Additionally, 43% of DT120-treated patients achieved at least a 50% reduction in HAM-A scores versus 16% with placebo, while 14% achieved remission versus 4% on placebo.The company said DT120 was generally well tolerated, with treatment-emergent adverse events usually being mild to moderate, transient and typically occurring on the day of dosing. No new safety signals were identified, including no signal for suicidality or suicidal behaviour.LSD perception problemStill, Sandeep Nayak, assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine, recently told FirstWord that relative to psilocybin-based programmes like Compass Therapeutics' COMP360, an LSD-based therapeutic such DT120 may have a steeper hill to climb when it comes to a patient's perception of safety."The average person, at least in the US, still thinks of psychedelics, and LSD in particular, as being an extremely risky, dangerous thing to do," Nayak said (see – KOL Views Q&A: Can Definium's psychedelic antidepressant defy LSD's negative branding?).Another anxiety studyMeanwhile, a second Phase III GAD study, called Panorama, is expected to report topline results in September and includes both 100-µg and 50-µg arms. The primary endpoint will assess change in HAM-A score from baseline to week 12 for DT120 100 µg versus placebo; the 50-µg arm is intended to help preserve the study's blinding by making it harder for participants to guess which treatment they received.Definium's GAD results come less than two months after it raised $805 million in a follow-on offering following DT120's positive Phase III MDD results. In that study, DT120 produced an 8.1-point placebo-adjusted improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) scores at week 6, with benefit persisting through week 12.Definium is also developing DT120 in post-traumatic stress disorder.

New York-based Definium Therapeutics (Nasdaq: DFTX) reported positive topline results from the Phase III Voyage study of DT120 ODT, its proprietary orally disintegrating formulation of lysergide D-tartrate (LSD), in generalized anxiety disorder (GAD), marking the second consecutive Phase III win for the compound in two months. Definium is now on a plausible path toward an NDA submission. Voyage is a randomized, double-blind, placebo-controlled study that enrolled 214 adults aged 18 to 74 with DSM-5-confirmed GAD and a Hamilton Anxiety Rating Scale (HAM-A) total score of at least 20, across approximately 35 US sites. A single 100 µg dose of DT120 ODT produced a least squares mean HAM-A reduction of 11.6 points at Week 12, versus 6.2 points for placebo — a placebo-adjusted difference of 5.4 points (p<0.0001, Cohen's d=0.81). All multiplicity-controlled secondary endpoints were met, including HAM-A change at Week 1 and Clinical Global Impression-Severity (CGI-S) change at Day 2. Response rates (HAM-A ≥50% reduction) at Week 12 were 43% versus 16% for placebo. Adverse events were mild to moderate, transient, and concentrated on the dosing day; no suicidality signal was observed. The average time to meeting end-of-session checklist criteria was 6.4 hours, with 92% of participants clearing the threshold by hour 8. LSD is a classic serotonergic psychedelic that acts partly through serotonin 5-HT2A receptor activation. Definium hypothesizes that downstream changes in neuroplasticity contribute to the sustained symptom improvements observed after a single administration, although the precise therapeutic mechanism remains uncertain. The Voyage result follows the positive Phase III Emerge readout in major depressive disorder (MDD) in June 2026, in which a single DT120 ODT dose produced a placebo-adjusted MADRS reduction of 8.1 points at Week 6 (p<0.0001). The company holds FDA Breakthrough Therapy Designation for DT120 ODT in GAD, which provides a basis for an expedited regulatory dialogue. A second pivotal GAD study, Panorama, includes an additional 50 µg low-dose arm specifically designed to confound participants' ability to identify their dose condition — a methodological response to the functional unblinding problem inherent to psychedelic trials. Definium said Panorama topline results are expected in September 2026. If Panorama confirms the Voyage signal, Definium would hold two GAD datasets and two MDD datasets. The competitive landscape for DT120 ODT in GAD remains sparse at the pivotal stage. Sumitomo Pharma and Otsuka's ulotaront (SEP-363856), a TAAR1 and 5-HT1A receptor agonist, is in Phase II/III development for GAD, while AbbVie's ABBV-932, a dopamine D3-receptor modulator, is in earlier clinical investigation as an adjunct. Neither has Phase III data. In the broader psychedelic therapeutics field, UK-based Compass Pathways (Nasdaq: CMPS) has reported positive results from two Phase III trials of its synthetic psilocybin compound COMP360 in treatment-resistant depression and is pursuing a rolling NDA submission, but targets a different indication. FDA's handling of the COMP360 submission could provide an important regulatory precedent for psychedelic therapies, particularly around supervised administration, functional unblinding and post-dose monitoring. Definium raised USD 805 million in a June 2026 public offering to fund pre-commercialization activities and ongoing clinical development - an indication of investor confidence behind the firm. The single-dose, supervised-administration model DT120 ODT requires will demand new access and reimbursement frameworks, and the September Panorama readout remains the next material data point before any NDA filing. Access the AllSci platform to explore the science behind the news. Spot something wrong? Report an issue with this article