Search

US-20260124183-A1 - METHODS OF TREATING SPINOCEREBELLAR ATAXIAS

US20260124183A1US 20260124183 A1US20260124183 A1US 20260124183A1US-20260124183-A1

Abstract

Provided is a method for treating spinocerebellar ataxia genotype type 3 in a patient in need thereof, including administering to the patient a dosage form comprising an effective amount of troriluzole hydrochloride monohydrate. Also provided is a dosage form including troriluzole hydrochloride monohydrate in an amount effective to treat spinocerebellar ataxia genotype type 3 in a patient in need thereof.

Inventors

  • Vladimir Coric
  • MELISSA BEINER
  • IRFAN QURESHI
  • GILBERT L'ITALIEN

Assignees

  • BIOHAVEN THERAPEUTICS LTD.

Dates

Publication Date
20260507
Application Date
20230523

Claims (20)

  1. 1 . A method for treating spinocerebellar ataxia genotype type 3 in a patient in need thereof, comprising administering to the patient a dosage form comprising an effective amount of troriluzole hydrochloride monohydrate.
  2. 2 . The method of claim 1 , wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for forty eight weeks, and wherein the patient at week 48 showed a least squares [LS] mean change difference of −0.55 compared to placebo (nominal p-value=0.053, 95% CI: −1.12, 0.01).
  3. 3 . (canceled)
  4. 4 . The method of claim 1 , wherein the dosage form is in the form of a capsule or tablet.
  5. 5 . (canceled)
  6. 6 . The method of claim 4 , wherein the dosage form is in the form of an orally disintegrating tablet.
  7. 7 . The method of claim 1 , wherein the dosage form comprises 200 mg of troriluzole hydrochloride monohydrate, and wherein the dosage form is administered to the patient daily.
  8. 8 . The method of claim 1 , wherein the dosage form comprises 100 mg of troriluzole hydrochloride monohydrate, and wherein the dosage form is administered to the patient twice a day.
  9. 9 . The method of claim 1 , wherein the dosage form is administered daily for at least four weeks.
  10. 10 . The method of claim 9 , wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for four weeks, and wherein the patient at week 4 showed a least squares [LS] mean change difference of at least −0.46 compared to placebo.
  11. 11 . (canceled)
  12. 12 . The method of claim 1 , wherein the dosage form is administered daily for at least eight weeks.
  13. 13 . The method of claim 12 , wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for eight weeks, and wherein the patient at week 8 showed a least squares [LS] mean change difference of at least −0.12 compared to placebo.
  14. 14 . (canceled)
  15. 15 . The method of claim 1 , wherein the dosage form is administered daily for at least twelve weeks.
  16. 16 . The method of claim 15 , wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for twelve weeks, and wherein the patient at week 12 showed a least squares [LS] mean change difference of at least −0.46 compared to placebo.
  17. 17 . (canceled)
  18. 18 . The method of claim 1 , wherein the dosage form is administered daily for at least twenty-four weeks.
  19. 19 . The method of claim 18 , wherein the dosage form comprising 200 mg of troriluzole hydrochloride monohydrate is administered to the patient daily for twenty-four weeks, and wherein the patient at week 24 showed a least squares [LS] mean change difference of at least −0.17 compared to placebo.
  20. 20 . (canceled)

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63/344,917 filed May 23, 2023, and all the benefits accruing therefrom under 35 U.S.C. § 119, the content of which is herein incorporated in its entirety by reference. FIELD OF THE INVENTION The present invention relates to methods of treating spinocerebellar ataxias. In particular, this application relates to methods of treating spinocerebellar ataxia genotype type 3. BACKGROUND OF THE INVENTION Ataxia is a disorder of the central nervous system, wherein the patient is unable to coordinate muscles for the execution of voluntary movement, see, e.g., Klockgether, T. “Ataxias” in Parkinsonism and Related Disorders 13, S391-S394, 2007. Typical symptoms of ataxia are gait dysfunctions, imbalance, impaired limb coordination and altered speech. In many ataxia disorders, the ataxia is due to degeneration of the cerebellar cortex and its afferent or efferent fiber connections. Typical affected brain regions are cerebellum, posterior column, pyramidal tracts and basal ganglia. Ataxia may lead to a decreased motoneuron function. Spinocerebellar ataxia (“SCA”) is a group of inherited brain disorders, which affects cerebellum, a part of brain vital to coordination of physical movement, and sometimes spinal cord. Spinocerebellar ataxia can be classified into ataxias associated with translated GAG repeat expansions (SCA types 1, 2, 3, 6, 7 and 17), ataxias associated with untranslated repeat expansions in non-coding regions (SCA types 10 and 12), ataxias associated with point-mutations (SCA types 5, 13, 14 and 27). The most common SCAs include type 1, 2, 3, 6, 7, 8 and 10. SCA1 often produces gait ataxia, limb ataxia, and dysarthria, with brainstem involvement but little cognitive abnormality. SCA2 is notable for the association of ataxia and dysarthria with slow saccadic eye movements and polyneuropathy. SCA3 (also known as Machado-Joseph disease) is often accompanied by eyelid retraction, reduced blinking, external ophthalmoplegia, dysarthria, dysphagia, and sometimes parkinsonism or peripheral neuropathy. SCA6 is comparatively less severe, typically progresses more slowly, is more limited to cerebellar involvement than other SCAs, and has a later age of onset. SCA7 is distinguished by retinal degeneration leading to blindness, in addition to ataxia. Overall, there is significant symptom overlap among these SCAs. The shared symptomatic manifestations of the SCAs may reflect common pathology affecting cerebellar purkinje cell fibers. There are currently no United States Food and Drug Administration (“FDA”) approved medications for the treatment of SCAs. There remains a need for effective medications to treat various types of SCA as well as a broader spinocerebellar ataxia population. SUMMARY OF THE INVENTION The present invention is directed to methods of treating spinocerebellar ataxia genotype type 3 and dosage forms for such treatment. In an embodiment, provided is a method for treating spinocerebellar ataxia genotype type 3 in a patient in need thereof, including administering to the patient a dosage form comprising an effective amount of troriluzole hydrochloride monohydrate. In another embodiment, provided is a dosage form including troriluzole hydrochloride monohydrate in an amount effective to treat spinocerebellar ataxia genotype type 3 in a patient in need thereof. BRIEF DESCRIPTION OF THE DRAWINGS These and/or other aspects will become apparent and more readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings in which: FIG. 1 a graph showing f-SARA change from randomization baseline to week 48 in f-SARA total score by treatment arm among all SCA patients (nominal p=0.76); FIG. 2 is a graph showing f-SARA change from randomization baseline to week 48 in f-SARA total score by treatment arm among SCA3 patients (with baseline f-SARA Gait Item score included as covariate, nominal p=0.53); FIG. 3 is a graph showing f-SARA change from randomization baseline to week 48 in f-SARA total score by treatment arm among SCA3 patients who could walk without assistance at baseline (nominal p=0.031); and FIG. 4 is a table showing frequency of treatment-emerging adverse events (TEAE) of fall among various patient groups. DETAILED DESCRIPTION OF THE INVENTION The following detailed description is provided to aid those skilled in the art in practicing the present invention. Exemplary embodiments will hereinafter be described in detail. However, these embodiments are only exemplary, and the present disclosure is not limited thereto but rather is defined by the scope of the appended claims. Those of ordinary skill in the art may make modifications and variations in the embodiments described herein without departing from the spirit or scope of the present disclosure. Accordingly, the embodiments are merely described below, by referring to structures and schemes