A recently completed phase 1 program found that ITI-1284 ODT-SL was rapidly absorbed into the systemic circulation, was metabolically stable, and resulted in high systemic exposure.
Intra-Cellular Therapies recently announced the expansion of its central nervous system (CNS) pipeline with ITI-1284 ODT-SL, with plans to develop the agent for the treatment of dementia-related psychosis and the treatment of certain depressive disorders in elderly patients.1
ITI-1284 ODT-SL is formulated as an oral solid dosage form that dissolves instantaneously when placed under the tongue and was developed in collaboration with Catalent using its proprietary Zydis ODT (orally disintegrating tablet) fast-dissolving formulation.
The announcement follows the completion of ITI-1284 ODT-SL’s phase 1 program, where the drug was rapidly absorbed into the systemic circulation, was metabolically stable, and resulted in high systemic exposure. Throughout the single and multiple-ascending dose studies, the safety, tolerability, and pharmacokinetics of ITI-1284 were evaluated among health volunteers and healthy elderly volunteers aged 65 years and older.
In these studies, there were no reported serious adverse events (AEs) in either age group. Additionally, reported AEs in the elderly cohort were infrequent, with transient dry mouth being the most common AE documented.
The results of the studies within the phase 1 program are the premise for new plans to initiate phase 2 studies evaluating ITI-1284 ODT-SL for the treatment of behavioral disturbances in dementia, dementia-related psychosis, and certain depressive disorders in elders.
ITI-1284 is a deuterated form of lumateperone, a new molecular entity formulated as an oral disintegrating tablet for sublingual administration. In February, Intra-Cellular announced that it had submitted supplemental new drug applications (sNDAs) to the FDA for 2 indications for lumateperone.2
"2020 was a transformational year for our company with the launch of our first product, CAPLYTA. I am proud of the important progress that our organization has achieved. We navigated unprecedented and challenging COVID-19 circumstances and still accomplished key commercial and clinical development milestones,” Sharon Mates, PhD, chairman and chief executive officer, Intra-Cellular Therapies, said in a statement in February. "We look forward to continuing our progress as we seek to expand our CAPLYTA label to include patients with bipolar depression. We are excited about our late-stage lumateperone programs in depressive disorders and the advancement of a long-acting injectable formulation into clinical trials as well as further expanding our pipeline with ITI-1284.”3
The first indication is as a monotherapy, and the second is as an adjunctive therapy with lithium or valproate for the treatment of depressive episodes associated with bipolar 1 or 2 disorder (bipolar depression) in adults. If approved, lumateperone, marketed as Caplyta, would be the first therapy indicated for the treatment depressive episodes associated with bipolar 1 or 2 disorder both as a monotherapy and as adjunctive therapy.
This addition of ITI-1284 to the pipeline for dementia-related psychosis marks the promising state of development for the condition. It comes just days before pimavanserin (Nuplazid; Acadia Pharmaceuticals), a selective serotonin inverse agonist and antagonist preferentially targeting 5HT2A receptors, reaches the FDA for a decision on its future in the therapeutic arsenal for this indication. The Acadia had its sNDA accepted by the FDA for the treatment of hallucinations and delusions associated with dementia-related psychosis in July 2020.4 With a prescription drug user fee act (PDUFA) date of April 3, 2021, the treatment could become the first therapy approved for these indications.