KPT-350 / Karyopharm - LARVOL DELTA

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB100 Administered Orally to Adults With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P1; N=49; Completed; Sponsor: Biogen; Recruiting ➔ Completed

Clinical • Trial completion • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders

"Biogen is developing treatments for sporadic ALS as well. Check out BIIB100 and BIIB105. A treatment discovery for a specific familial ALS might uncover ways to treat sporadic ALS." (@MMoutsoulas)

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB100 Administered Orally to Adults With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P1; N=48; Recruiting; Sponsor: Biogen; Trial completion date: Dec 2020 ➔ Mar 2021; Trial primary completion date: Dec 2020 ➔ Mar 2021

Clinical • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders

In vivo KPT-350 treatment decreases cortical hyperexcitability following traumatic brain injury. (PubMed, Brain Inj) - "KPT-350 can prevent cortical hyperexcitability and reduce the loss of parvalbumin-(+) GABAergic inhibitory neurons, making it a potential therapeutic option for preventing PTE."

Journal • Preclinical • CNS Disorders • Epilepsy • Vascular Neurology • Glial Fibrillary Acidic Protein

Inhibition of Nuclear Pore Export Ameliorates Lupus via Modulation of Plasma Cell Generation and Survival (ACR-ARHP 2019) - "Finally, we used flow cytometry to enumerate cycling and non-cycling splenic and BM plasma cells in Edu labelled LPM after short-term therapy with KPT-335 (7.5 mg/kg) or vehicle (n = 8 mice/group)...There was a significant decrease in CXCL13 staining (Control vs treated, p< 0.0001) and the size of follicular dendritic cells networks (Control vs treated, p< 0.0001) in spleens of mice orally treated with KPT-350 at 7.5 mg/kg for 8 weeks (3 administrations/week)... Our data demonstrate that SINEs disrupt NF-kB- dependent production of HC by stromal cells, thus impairing GC formation and compromising autoreactive PC generation. In addition, SINEs have a direct impact on PC survival, including long-lived plasma cells in the BM. ACR2019JRM"

BIIB100 improves motor function, slows DMD progression in animal models, study finds (Muscular Dystrophy News Today) - “…BIIB100 is also being explored as a potential treatment for amyotrophic lateral sclerosis. A Phase 1 trial (NCT03945279) is recruiting adults with this disorder to test the therapy’s safety, tolerability, and pharmacological profile.”

Trial status

The SINE Compound KPT-350 Blocks Dystrophic Pathologies in DMD Zebrafish and Mice. (PubMed, Mol Ther) - "Here, we demonstrate that SINE compound KPT-350 can ameliorate dystrophic-associated pathologies in the muscles of DMD models of zebrafish and mice. Thus, SINE compounds are a promising novel strategy for blocking dystrophic symptoms and could be used in combinatorial treatments for DMD."

Journal • Preclinical

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB100 Administered Orally to Adults With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P1; N=40; Recruiting; Sponsor: Biogen; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB100 Administered Orally to Adults With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P1; N=40; Not yet recruiting; Sponsor: Biogen

Clinical • New P1 trial