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AL 001

Drug Profile

AL 001

Alternative Names: AL-001

Latest Information Update: 24 Oct 2019

At a glance

  • Originator Alector
  • Class Antidementias; Immunotherapies; Monoclonal antibodies; Neuroprotectants; Recombinant proteins
  • Mechanism of Action Sortilin inhibitors
  • Orphan Drug Status

    Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.

    Yes - Dementia
  • New Molecular Entity Yes

Highest Development Phases

  • Phase II Dementia

Most Recent Events

  • 09 Oct 2019 Efficacy and safety data from a phase I trial in Dementia presented at the (Alzheimer's Association International Conference (AAIC-2019)
  • 09 Sep 2019 Phase-II clinical trials in Dementia in United Kingdom, USA, Netherlands, Italy, Germany, Canada (IV) (NCT03987295)
  • 09 Sep 2019 Alector initiates enrolment in a INFRONT phase II trial for Dementia in the UK, the USA, Germany, Italy, Netherland, Canada (NCT03987295)

Development Overview

Introduction

AL 001 is a microglia activating recombinant human anti-human sortilin (SORT1) monoclonal antibody being developed by Alector for the treatment of frontotemporal dementia (FTD). FTD has been linked to a genetic mutation that hampers the production of progranulin (PGRN). AL 001 blocks the breakdown of PGRN and increase PGRN levels by binding to receptors on the surface of both microglia and neurons that facilitate PGRN degradation. Increased levels of PGRN sustains the survival of neurons and moderates the potentially harmful inflammatory responses of immune system cells including microglia. Clinical development is underway in the US.

Key Development Milestones

In October 2019, Alector initiated an enrolment in INFRONT phase II trial to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and effect on clinical outcome assessments (COAs) in patients with frontotemporal dementia with a granulin or C9orf72 mutation (NCT03987295; AL001-2). The multicenter, open-label trial was designed to enrol 32 patients in the UK, Netherlands, Italy, Germany, Canada and the US. In October 2019, the company released safety and efficacy data from the trial at the Alzheimer's Association International Conference (AAIC-2019) [1] [2] [3] .

In August 2018, Alector reported that the US FDA Office of Orphan Products Development granted orphan drug designation to AL 001 for the treatment of frontotemporal dementia [4] .

In September 2018, Alector initiated first-in-human phase I trial to evaluate safety, tolerability, pharmacokinetics and pharmacodynamic properties of AL 001 in healthy volunteers and in the patients with frontotemporal dementia with granulin mutation (AL001-1;NCT03636204). The completed phase 1 healthy volunteer single ascending portion of the AL 001 study successfully met its primary objective of safety with no drug-related serious adverse events and demonstrated proof-of-mechanism in the central nervous system (CNS). In April 2019, Alector announced dosing of the first patient in the multiple ascending dose phase 1b study that will enrol frontotemporal dementia (FTD) patients with a mutation in the progranulin gene to assess safety and pharmacodynamics monitor target specific biomarkers. The randomised trial intends to enrol approximately 60 healthy volunteers and patients in the US and expected to expand in Canada, Netherlands and in the UK [5] [6] . In July 2019, the company presented safety and efficacy data of AL 001 at the Alzheimer's Association International Conference 2019 (AAIC-2019) [7] .

Financing information

In July 2018, Alector secured $US133 million in Series E financing round. The company has previously raised $US282 million. The company expect to utilize the proceeding from the financing to advance Alector’s clinical programs and expand the company’s discovery platform [8] .

Patent Information

Alector 3 patent families directed to PGRN programs, which include 1 issued US patent, 4 pending U.S. non-provisional patent applications, 1 pending US provisional patent application, and multiple pending foreign patent applications covering the compositions and uses of our PGRN program product candidates and 1 US non-provisional patent application to methods of screening. 2 patent families are expected to expire in 2036 and the third patent family, assuming that the necessary non-provisional patent applications are timely filed and all other applicable requirements are satisfied for the US provisional patent application, in 2039, in both cases excluding any patent term adjustments and any patent term extensions.

Drug Properties & Chemical Synopsis

  • Route of administration IV, Parenteral
  • Formulation unspecified
  • Class Antidementias, Immunotherapies, Monoclonal antibodies, Neuroprotectants, Recombinant proteins
  • Target Sortilin
  • Mechanism of Action Sortilin inhibitors
  • WHO ATC code

    N06D-X (Other anti-dementia drugs)

  • EPhMRA code

    N7X (All other CNS drugs)

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Dementia in patients with frontotemporal Dementia in patients with Frontotemporal dementia - Phase II Canada, Germany, Italy, Netherlands, USA, United Kingdom IV / unspecified Alector 09 Sep 2019

Orphan Status

Indication Patient Segment Country Organisation Event Date
Dementia - USA Alector 08 Aug 2018

Commercial Information

Involved Organisations

Organisation Involvement Countries
Alector Originator USA
Alector Owner USA

Scientific Summary

Adverse Events

Results from phase I INFRONT study showed that AL 001 was well tolerated and was safe in patients with frontotemporal dementia with a granulin mutation [1] [6] .

In a phase I trial, AL 001 was generally safe and well tolerated through the highest dose assessed, healthy volunteers and in patients with frontotemporal dementia [7] [6] .

Therapeutic Trials

Results from the phase I INFRONT study showed that AL 001 was able to restore the level of progranulin in patients with frontotemporal dementia with a granulin mutation back to the normal range [1] [6] .

Results from the single ascending dose part of the phase I trial of AL 001, demonstrated dose dependent increase in PGRN levels in plasma and in cerebrospinal fluid in healthy volunteers and in patients with frontotemporal dementia [7] [6] .

Future Events

Expected Date Event Type Description Updated
01 Dec 2020 Trial Update Alector plans a phase III trial for in 2020 [2] 14 Oct 2019
30 Jun 2020 Trial Update Alector plans a phase II trial for Dementia in the first half of 2020 [9] 04 Apr 2019
31 Jul 2019 Trial Update Alector plans a phase-II trial for Dementia in Canada, Germany, Italy, Netherlands, United Kingdom and USA in July 2019 (IV, Infusion) (NCT03987295) 14 Oct 2019
30 Jun 2019 Trial Update Alector plans a phase I trial for Dementia in the first half of 2019 [9] 14 Oct 2019
15 Sep 2018 Trial Update Alector plans a phase I trial for Dementia in USA in September 2018 (NCT03636204) (700298951) 03 Oct 2018

Development History

Event Date Update Type Comment
09 Oct 2019 Scientific Update Efficacy and safety data from a phase I trial in Dementia presented at the (Alzheimer's Association International Conference (AAIC-2019) [1] Updated 14 Oct 2019
09 Sep 2019 Phase Change - II Phase-II clinical trials in Dementia in United Kingdom, USA, Netherlands, Italy, Germany, Canada (IV) (NCT03987295) Updated 14 Oct 2019
09 Sep 2019 Trial Update Alector initiates enrolment in a INFRONT phase II trial for Dementia in the UK, the USA, Germany, Italy, Netherland, Canada [2] (NCT03987295) Updated 14 Oct 2019
09 Sep 2019 Trial Update Alector plans a phase III trial for in 2020 [2] Updated 14 Oct 2019
14 Jul 2019 Scientific Update Efficacy and adverse events data from a phase I trial in Dementia presented at the Alzheimer's Association International Conference 2019 (AAIC-2019) [7] Updated 24 Oct 2019
17 Jun 2019 Trial Update Alector plans a phase-II trial for Dementia in Canada, Germany, Italy, Netherlands, United Kingdom and USA in July 2019 (IV, Infusion) (NCT03987295) Updated 14 Oct 2019
04 Apr 2019 Trial Update Alector plans a phase I trial for Dementia in the first half of 2019 [9] Updated 14 Oct 2019
04 Apr 2019 Trial Update Alector plans a phase II trial for Dementia in the first half of 2020 [9] Updated 04 Apr 2019
28 Mar 2019 Patent Information Alector has patents pending for PGRN program in USA [9] Updated 04 Apr 2019
14 Sep 2018 Phase Change - I Phase-I clinical trials in Dementia in USA (IV)(NCT03636204) Updated 03 Oct 2018
17 Aug 2018 Trial Update Alector plans a phase I trial for Dementia in USA in September 2018 (NCT03636204) Updated 03 Oct 2018
08 Aug 2018 Regulatory Status AL 001 receives Orphan Drug status for Dementia in USA [4] Updated 17 Aug 2018
25 Jul 2018 Phase Change Early research in Dementia in USA (Parenteral) [8] Updated 30 Jul 2018

References

  1. Alector Announces Data from On-going Phase 1b Trial Demonstrating that AL001 Reverses Progranulin Deficiency in Frontotemporal Dementia Patients.

    Media Release
  2. Alector Initiates Phase 2 Trial of AL001 in Patients with Frontotemporal Dementia.

    Media Release
  3. A Phase 2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AL001 in Heterozygous Carriers of Granulin or C9ORF72 Mutations Causative of Frontotemporal Dementia

    ctiprofile
  4. Alector Receives Orphan Drug Designation from the U.S. FDA for AL001 for the Treatment of Frontotemporal Dementia.

    Media Release
  5. Alector Announces First Frontotemporal Dementia Patient Dosed in Phase 1b Study of AL001.

    Media Release
  6. A First in Human Phase 1 Study in Healthy Volunteers and in Participants With Frontotemporal Dementia (FTD) With Granulin Mutation

    ctiprofile
  7. Paul R, Ward M, Siddiqui O, Hagey M, Long H, King R, et al. A phase 1 study of AL001 in healthy volunteers and frontotemporal dementia patients carrying a granulin mutation. AAIC-2019 2019; abstr. 35586.

    Available from: URL: https://eventpilotadmin.com/web/page.php?page=IntHtml&project=AAIC19&id=35586
  8. Alector Announces $133 Million in Series E Financing to Advance Broad Portfolio of Immuno-Neurology and Immuno-Oncology Programs.

    Media Release
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