Therapeutics

TW001

Tools

Back to the Top

Overview

Name: TW001
Synonyms: FNP122, FAB122, oral edaravone
Therapy Type: Small Molecule (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease, Amyotrophic Lateral Sclerosis
U.S. FDA Status: Alzheimer's Disease (Phase 2), Amyotrophic Lateral Sclerosis (Phase 3)
Company: Treeway B.V.

Background

TW001 is a new oral formulation of edaravone, an antioxidant drug marketed in the U.S. and Japan to treat amyotrophic lateral sclerosis.

Oxidative stress plays a role in Alzheimer’s disease, and edaravone has shown beneficial effects in multiple cellular and animal models of Aβ toxicity (e.g., Feng et al., 2019; Feng et al., 2020; Jiao et al., 2015). An oral formulation of edaravone dose-dependently reversed behavior deficits in APP-PS-1 mice (Parikh et al., 2018).

Findings

In 2018, Treeway reported Phase 1 results in 18 healthy volunteers indicating that TW001 was safe and that the bioavailability of a single oral dose of 140 mg exceeded that of a one-hour infusion of 60 mg of Radicava, an FDA-approved oral edaravone.

TW001 received Orphan Drug Designation by the European Medicines Agency in 2014 and by the Food and Drug Administration in 2015.

In November 2021, Treeway, in collaboration with the Spanish company Ferrer, began a Phase 3 trial of TW001, now also called FNP122 or FAB122, in people with ALS. Called ADORE, it is enrolling 300 patients at 38 sites across Europe, to compare safety and efficacy of a 100 mg daily dose to placebo. The study will run until mid-2024, and offers an open-label safety extension.

In March 2023, Treeway began a Phase 2 trial of TW001 in Alzheimer's patients. It plans to enroll 60 people with early AD, defined as an MMSE score greater than 20, plus CSF or PET evidence of brain amyloid. Dosing will be 100 mg daily for three months, against primary outcomes of adverse events, and plasma and CSF biomarkers of oxidative stress. Other outcomes include pharmacokinetics, plasma biomarkers of AD pathology and neurodegeneration, and urine oxidative stress markers, as well as cognition, and function. The trial is running at five sites in the Netherlands and Croatia, with completion expected in June 2024. The design is published (Oosthoek et al., 2023).

For TW001/FNP122 trials, see clinicaltrials.gov

Last Updated: 02 Jan 2024

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

Therapeutics Citations

  1. Edaravone

Paper Citations

  1. Oosthoek M, Lili A, Almeida A, van Loosbroek O, van der Geest R, de Greef-van der Sandt I, van Bokhoven P, Sikkes SA, Teunissen CE, Vijverberg EG. ASURE Clinical Trial Protocol: A Randomized, Placebo-Controlled, Proof-of-Concept Study Aiming to Evaluate Safety and Target Engagement following Administration of TW001 in Early Alzheimer's Disease Patients. J Prev Alzheimers Dis. 2023;10(4):669-674. PubMed.
  2. Feng T, Yamashita T, Shang J, Shi X, Nakano Y, Morihara R, Tsunoda K, Nomura E, Sasaki R, Tadokoro K, Matsumoto N, Hishikawa N, Ohta Y, Abe K. Clinical and Pathological Benefits of Edaravone for Alzheimer's Disease with Chronic Cerebral Hypoperfusion in a Novel Mouse Model. J Alzheimers Dis. 2019;71(1):327-339. PubMed.
  3. Feng T, Yamashita T, Sasaki R, Tadokoro K, Matsumoto N, Hishikawa N, Abe K. Protective effects of edaravone on white matter pathology in a novel mouse model of Alzheimer's disease with chronic cerebral hypoperfusion. J Cereb Blood Flow Metab. 2020 Oct 26;:271678X20968927. PubMed.
  4. Jiao SS, Yao XQ, Liu YH, Wang QH, Zeng F, Lu JJ, Liu J, Zhu C, Shen LL, Liu CH, Wang YR, Zeng GH, Parikh A, Chen J, Liang CR, Xiang Y, Bu XL, Deng J, Li J, Xu J, Zeng YQ, Xu X, Xu HW, Zhong JH, Zhou HD, Zhou XF, Wang YJ. Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits. Proc Natl Acad Sci U S A. 2015 Apr 21;112(16):5225-30. Epub 2015 Apr 6 PubMed.
  5. Parikh A, Kathawala K, Li J, Chen C, Shan Z, Cao X, Wang YJ, Garg S, Zhou XF. Self-nanomicellizing solid dispersion of edaravone: part II: in vivo assessment of efficacy against behavior deficits and safety in Alzheimer's disease model. Drug Des Devel Ther. 2018;12:2111-2128. Epub 2018 Jul 9 PubMed.

External Citations

  1. clinicaltrials.gov

Further Reading

No Available Further Reading