Cystic fibrosis digest - 2021

Cystic fibrosis digest - 2021

ENaCs – Updates from Arrowhead and Enterprise Therapeutics

ARO-ENaC (RNAi) – Arrowhead Pharmaceuticals

  • Arrowhead Pharmaceuticals voluntarily paused AROENaC1001, a Phase 1/2 clinical study of ARO-ENaC
  • Regulatory agencies, institutional review boards, and investigators were notified immediately
  • Reason: Preliminary update from an ongoing chronic toxicology study in rats showed unexpected signals of local lung inflammation
  • Trial details: AROENaC1001; Phase 1/2, Pulmonary cystic fibrosis; N=92; ARO-ENaC; Primary outcomes: AEs; PCD: Dec’21; Suspended; Location: Australia, New Zealand (For full story click here)

ETD001 (ENaC inhibitor) – Enterprise Therapeutics

  • Enterprise Therapeutics dosed healthy volunteers in a Phase 1 trial for its inhaled therapy, ETD001 (For full story click here)

Arrowhead ENaC pauses while EDT001 jumps on the ENaC bandwagon

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CI Scientists Commentary:

  • Arrowhead to decide the path of clinical development after gaining additional insights from preclinical studies
  • Arrowhead’s stocks plummeted by 26.5% and are now at $62.49
  • Other companies both big and small have failed for similar reasons

Company

Asset

Stage of development

Reason for discontinuation

Novartis

QAU 145

Phase 2

Adverse effects/tolerability issues

QBW276

Phase 2

Terminated due to strategic reasons

Boehringer Ingelheim

BI 443651

Phase 1

Discontinued due to palatability issues

BI 1265162

Phase 2

Phase 2 trial terminated; strategic reasons

AstraZeneca

AZD5634

Phase 1

AZD5634 did not have a significant impact on mucociliary clearance when compared with placebo

Gilead

GS 9411

Phase 1

Serious adverse effects – Acute hyperkalemia

Vertex/Parion

VX-371

Phase 2

Discontinued due to lack of efficacy

Spyryx Biosciences

SPX-101

Phase 2

Discontinued due to lack of efficacy

Ionis

Ionis-Enac-2.5-Rx

Phase 2

Based on the long-term preclinical toxicology studies

  • Apart from Gilead, other ENaCs were evaluated as a monotherapy
  • Unlike other CF therapies, EDT001 MOA is regardless of CFTR mutation. It will be interesting to look what will be Enterprise strategy in Phase 2 studies

– Dr. Kowndinya, CI Scientists

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