Ulixacaltamide

Last updated

Ulixacaltamide
INN: Ulixacaltamide
Ulixacaltamide.svg
Clinical data
Other names
  • PRAX-944
  • Z-944
Routes of
administration 		Oral
Drug class T-type calcium channel blocker
Legal status
Legal status
  • US:Investigational (Breakthrough Therapy)
  • Investigational
Identifiers
  • N-[[1-[2-(tert-Butylamino)-2-oxoethyl]piperidin-4-yl]methyl]-3-chloro-5-fluorobenzamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
Formula C19H27ClFN3O2
Molar mass 383.89 g·mol−1
3D model (JSmol)
  • CC(C)(C)NC(=O)CN1CCC(CC1)CNC(=O)C2=CC(=CC(=C2)Cl)F
  • InChI=1S/C19H27ClFN3O2/c1-19(2,3)23-17(25)12-24-6-4-13(5-7-24)11-22-18(26)14-8-15(20)10-16(21)9-14/h8-10,13H,4-7,11-12H2,1-3H3,(H,22,26)(H,23,25)
  • Key:JOCLITFYIMJMNK-UHFFFAOYSA-N

Ulixacaltamide (developmental codes PRAX-944 and Z-944) is an investigational new drug developed by Praxis Precision Medicines for the treatment of essential tremor (ET). [1] It is a small molecule designed to selectively inhibit T-type calcium channels, reducing the abnormal neuronal burst firing in the cerebello-thalamo-cortical (CTC) circuit that is believed to cause tremors. [2]

Contents

In October 2025, the drug met its primary endpoints in the pivotal Phase 3 Essential3 clinical program. [3] Following these results, the U.S. Food and Drug Administration (FDA) granted ulixacaltamide Breakthrough Therapy Designation in December 2025. [4] The company has announced plans to submit a New Drug Application (NDA) by mid-February 2026.

Medical uses

Ulixacaltamide is being developed specifically for the treatment of essential tremor in adults. If approved, it would represent a new pharmacological class of treatment for the condition, distinct from the current standard-of-care agents such as propranolol (a beta-blocker) and primidone (an anticonvulsant). [2]

In December 2025, the FDA granted the drug Breakthrough Therapy Designation, a status intended to expedite the development and review of drugs for serious conditions where preliminary clinical evidence indicates the drug may demonstrate substantial improvement over available therapies. [4]

Mechanism of action

Ulixacaltamide is a selective blocker of T-type calcium channels (Cav3.1, Cav3.2, and Cav3.3 isoforms). [2]

Research suggests that the involuntary rhythmic shaking characteristic of essential tremor is driven by abnormal oscillatory activity within the cerebello-thalamo-cortical circuit. Specifically, T-type calcium channels play a key role in generating "burst firing" patterns in neurons within this pathway. By inhibiting these channels, ulixacaltamide is designed to suppress this pathological burst firing and reduce tremor amplitude without causing the widespread central nervous system depression often associated with non-selective treatments. [5]

History

Discovery and early development

The compound was originally discovered by Zalicus Inc. (formerly Neuromed) and was known as Z-944. [6] It was later acquired by Praxis Precision Medicines and renamed PRAX-944.

Clinical trials

The drug's efficacy was evaluated in the Phase 2 "Essential1" study, which showed improvements in daily living activities scores. [5]

In 2025, Praxis completed the "Essential3" Phase 3 program, which consisted of two concurrent decentralized studies:

These positive results followed a February 2025 interim analysis by an Independent Data Monitoring Committee (IDMC) that had initially recommended discontinuing the study due to perceived futility. Praxis elected to continue the trial, ultimately achieving statistical significance in the final readout. [7]

Adverse effects

In Phase 3 clinical trials, ulixacaltamide was generally well-tolerated, with no drug-related serious adverse events reported. The most common adverse events (occurring in ≥10% of patients) included dizziness, constipation, euphoric mood, "brain fog" (cognitive disturbance), headache, and paresthesia. [3]

References

  1. ↑ "Ulixacaltamide - Praxis Precision Medicine". AdisInsight. Springer Nature Switzerland AG.
  2. 1 2 3 Scott L, Puryear CB, Belfort GM, Raines S, Hughes ZA, Matthews LG, et al. (June 2022). "Translational Pharmacology of PRAX-944, a Novel T-Type Calcium Channel Blocker in Development for the Treatment of Essential Tremor". Movement Disorders. 37 (6): 1193–1201. doi:10.1002/mds.28969. PMC   9310641 . PMID   35257414.
  3. 1 2 3 "Praxis Precision Medicines Announces Positive Topline Results from Two Pivotal Phase 3 Studies of Ulixacaltamide HCl in the Essential3 Program for Essential Tremor" (Press release). Praxis Precision Medicines. 2025-10-16. Retrieved 2026-01-13.
  4. 1 2 "FDA Grants Breakthrough Therapy Designation for Ulizacaltamine in Essential Tremor". HCPLive. 2025-12-29. Retrieved 2026-01-13.
  5. 1 2 "Building a Greater Understanding of Ulixacaltimide's Impact in Essential Tremor". NeurologyLive. 2023-09-18. Retrieved 2026-01-13.
  6. ↑ Tringham E, Powell KL, Cain SM, Kuplast K, Mezeyova J, Weerapura M, et al. (February 2012). "T-type calcium channel blockers that attenuate thalamic burst firing and suppress absence seizures". Science Translational Medicine. 4 (121): 121ra19. doi:10.1126/scitranslmed.3003120. PMID   22344687.
  7. ↑ "Praxis plots path to FDA after phase 3 wins in essential tremor". Fierce Biotech. 2025-10-16. Retrieved 2026-01-13.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.