Delving into the Latest Updates on AL-794 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

JNJ 5806, JNJ-5806, JNJ-64155806

Target

PA protein

Action

inhibitors

Mechanism

PA protein inhibitors(Polymerase acidic protein inhibitors)

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication-

Inactive Indication

Influenza, Human

Originator Organization

Janssen Global Services LLC

Active Organization-

Inactive Organization

Alios BioPharma, Inc.

Janssen Research & Development LLC

License Organization-

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

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The purpose of this study is to evaluate the safety and tolerability (including incidence of central nervous system [CNS] related events such as lightheadedness and dizziness), of multiple oral doses of AL-794 in healthy volunteers (HV). Also, to evaluate the pharmacokinetics of ALS-033719 and ALS-033927 in plasma after multiple oral doses of AL-794 in HV.

Start Date03 Mar 2018

Sponsor / Collaborator

Alios BioPharma, Inc.

NCT03126097

/ TerminatedPhase 1

A Phase 1, Open-label Study in Healthy Female Subjects to Investigate the Drug-drug Interaction Between JNJ-64155806 and Ethinylestradiol/Drospirenone

The primary purpose of this study is to evaluate the effect of single and multiple doses of JNJ-64155806 on the steady-state pharmacokinetics (PK) of ethinylestradiol and drospirenone and vice versa in healthy female participants.

Start Date13 Apr 2017

Sponsor / Collaborator

Janssen Research & Development LLC

NCT02888327

/ CompletedPhase 1

A Phase-1, Open-label, Four Group, Fixed-Sequence Study to Evaluate the Effect of AL-794 on the Pharmacokinetics of Oseltamivir, JNJ-63623872, and Probes for P-glycoprotein, CYP3A and OATP1B1 in Healthy Volunteers

This open-label, four group, fixed-sequence study will evaluate the safety and pharmacokinetic interaction of AL-794 on oseltamivir, JNJ-63623872 (formerly VX-787) and probes for P-glycoprotein, CYP3A and OATP1B1 in healthy volunteers.

Start Date31 Jul 2016

Sponsor / Collaborator

Alios BioPharma, Inc.

100 Clinical Results associated with AL-794

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100 Translational Medicine associated with AL-794

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100 Patents (Medical) associated with AL-794

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3

Literatures (Medical) associated with AL-794

01 Sep 2019·Antiviral researchQ2 · MEDICINE

Antivirals targeting the polymerase complex of influenza viruses

Q2 · MEDICINE

Review

Author: Hayden, Frederick G ; Hurt, Aeron C ; Mifsud, Edin J

Current influenza antivirals have limitations with regard to their effectiveness and the potential emergence of resistance. Encouragingly, several new compounds which inhibit the polymerase of influenza viruses have recently been shown to have enhanced pre-clinical and clinical effectiveness compared to the neuraminidase inhibitors, the mainstay of influenza antiviral therapy over the last two decades. In this review we focus on four compounds which inhibit polymerase function, baloxavir marboxil, favipiravir, pimodivir and AL-794 and discuss their clinical and virological effectiveness, their propensity to select for resistance and their potential for future combination therapy with the most commonly used neuraminidase inhibitor, oseltamivir.

07 Jan 2019·The Journal of infectious diseasesQ2 · MEDICINE

Antiviral Activity, Safety, and Pharmacokinetics of AL-794, a Novel Oral Influenza Endonuclease Inhibitor: Results of an Influenza Human Challenge Study

Q2 · MEDICINE

Article

Author: Chanda, Sushmita ; Fry, John ; Jekle, C Andreas ; Mitchell, Toni ; Yogaratnam, Jeysen ; Kakuda, Thomas N ; Fennema, Hein ; Symons, Julian A ; Van Remoortere, Pieter ; Boyce, Malcolm ; Rito, Jennifer ; Balaratnam, Ganesh ; Sahgal, Omair ; Gupta, Kusum

Background:

AL-794 is an orally active prodrug of ALS-033719, which selectively inhibits the endonuclease domain of influenza virus A and B polymerase.

Methods:

In a phase 1, double-blinded, randomized, placebo-controlled study, healthy subjects were inoculated intranasally with influenza virus (A/Perth/16/2009 H3N2) after confirmation of infection or on day 4. Subjects received 50 mg of AL-794, 150 mg of AL-794, or placebo twice daily for 5 days. Viral load, influenza symptoms, pharmacokinetics, and safety were evaluated.

Results:

A total of 61 subjects were inoculated. In 42 infected subjects, the mean peak viral load for 50-mg AL-794 recipients, 150-mg AL-794 recipients, and placebo recipients was 3.54, 2.77, and 3.72 log10 50% tissue culture infectious doses (TCID50)/mL, respectively. The mean influenza viral load area under the curve in the corresponding treatment groups was 137, 87.5, and 142 log10 TCID50/mL·h, respectively, and the median time to virus nondetection was 117, 75.3, and 108 hours, respectively. AL-794 was well tolerated, and no viral resistance to ALS-033719 was identified.

Conclusion:

Following oral administration of AL-794, significant dose-dependent antiviral activity was noted, with a greater decrease in viral load, symptoms, and mucus weight at the 150-mg dose, compared with the 50-mg dose, and no safety concerns for either dose or placebo.

Clinical Trials Registration:

NCT02588521.

01 Oct 2018·Antiviral therapyQ4 · MEDICINE

Phase I Study on Safety and Pharmacokinetics of a Novel Influenza Endonuclease Inhibitor, AL-794 (JNJ-64155806), following Single- and Multiple-Ascending doses in Healthy Adults

Q4 · MEDICINE

Article

Author: Gupta, Kusum ; Rito, Jennifer ; Yogaratnam, Jeysen ; Chanda, Sushmita ; Remoortere, Pieter Van ; Kakuda, Thomas N ; Mitchell, Toni ; Symons, Julian A ; Boyce, Malcolm ; Fry, John

Background:

This double-blind, first-in-human Phase I study evaluated pharmacokinetics, safety and tolerability of AL-794 (prodrug of ALS-033719), a potent endonucle-ase inhibitor of influenza A and B in healthy volunteers.

Methods:

Healthy adult volunteers were randomized to AL-794 (50–2,000 mg single ascending doses, fasting) or placebo (5 cohorts, n=6:2 AL-794: placebo/cohort) in part 1, and AL-794 (50–600 mg multiple ascending doses, twice-daily, fed or fasted) or placebo (3 cohorts, n=8:2 AL-794: placebo/cohort) for 7 days in part 2. In part 3, 8 healthy volunteers from part 1 received 450 mg AL-794 ( n=6) or placebo ( n=2) following a high-fat meal. All dosing was done with an oral suspension. Blood and urine samples for pharmacokinetics were collected at scheduled times and analysed for ALS-033719 and ALS-033927 (inactive glucuronide) plasma concentrations using LC-MS/MS.

Results:

ALS-033719 plasma concentrations increased dose proportionately up to 150 mg but less than proportionately above 150 mg. Steady-state was generally achieved by the third dose. ALS-033719 exposure increased following administration with a standard meal (19%–33%) or high-fat meal (3–3.6-fold). ALS-033927 was the major metabolite observed. Renal elimination was negligible (0.2%). Seventeen AL-794-treated healthy volunteers reported ≥1 treatment-emergent adverse event (TEAE; part 1: n=6, 24%; part 2: n=11, 69%). The most common TEAEs were headache (part 1: n=3; part 2: n=5) and dizziness (part 1: n=2; part 2: n=6).

Conclusions:

AL-794 up to 200 mg twice daily achieved ALS-033719 exposures which are expected to be efficacious and were generally tolerated. Further studies are planned to characterize safety and antiviral activity.

100 Deals associated with AL-794

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Influenza, Human	Phase 1	United Kingdom	Alios BioPharma, Inc.	31 Aug 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02588521 (Pubmed \| J Infect Dis)	Phase 1	Influenza, Human	61	AL-794 50 mg	fztmiwutor(wsbudyxwvd) = crkqtlfifz pwyoqlnrrm (lauzqrnpmb ) View more	-	07 Jan 2019
NCT02588521 (Pubmed \| J Infect Dis)	Phase 1	Influenza, Human	61	AL-794 150 mg	fztmiwutor(wsbudyxwvd) = pifouvcocx pwyoqlnrrm (lauzqrnpmb ) View more	-	07 Jan 2019
NCT02588521 (Pubmed \| Antivir Ther)	Phase 1	-	-	AL-794	hmffnmfusl(vmyvwgrpma) = increased following administration with a standard meal (19%-33%) or high-fat meal (3-3.6-fold) gvmxfafqpe (gkamjymdgk ) View more	-	01 Oct 2018