Delving into the Latest Updates on KP-1461 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target-

Mechanism

HIV replication inhibitors

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication-

Inactive Indication

HIV Infections

Originator Organization

Koronis Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Koronis Pharmaceuticals, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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The primary purpose of the study is to assess the safety and pharmacokinetics of KP-1461 given every 12 hours for 14 days when administered to HIV+ patients who have failed multiple highly active antiretroviral therapy (HAART) regimens. Patients currently on HAART will be required to discontinue all HAART medications for up to 6 weeks after screening eligibility has been determined.

Start Date01 Aug 2005

Sponsor / Collaborator

Koronis Pharmaceuticals, Inc.

100 Clinical Results associated with KP-1461

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100 Translational Medicine associated with KP-1461

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100 Patents (Medical) associated with KP-1461

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7

Literatures (Medical) associated with KP-1461

01 Feb 2013·AIDS Research and Human RetrovirusesQ4 · MEDICINE

Safety, Tolerability, and Efficacy of KP-1461 as Monotherapy for 124 Days in Antiretroviral-Experienced, HIV Type 1-Infected Subjects

Q4 · MEDICINE

Article

Author: Laurent, Jean-Pierre ; McRae, MaryPeace ; Clay, Patrick ; Redfield, Robert ; Lalezari, Jay ; Liporace, Ralph ; Sension, Michael ; Schneider, Stefan ; Hicks, Charles

Treatment of HIV infection with conventional antiretroviral therapy (ART) is a lifelong challenge with significant long-term risks of adverse events and treatment failure-induced HIV resistance being major concerns. One potential alternative to standard treatment is the use of viral decay accelerators, antiviral agents that theoretically can drive the rate of viral mutation beyond the compensatory capacity of the virus, thereby inducing viral extinction. One such drug, KP-1461, was tested in a population of HIV-infected persons not receiving ART to assess the safety, tolerability, and efficacy of the strategy in vivo. Of 24 highly treatment-experienced HIV-infected patients who received at least one dose of KP-1461, 13 completed the planned 4 months of monotherapy. The drug was generally well tolerated; it did not significantly affect either HIV viral load or CD4 lymphocyte count over the period of dosing. Pharmacokinetic sampling suggested adequate drug exposure was achieved. There were no new mutations induced by KP-1461 that changed viral susceptibility to standard antiretroviral agents. After the study was completed, analysis of more than 7 million base pairs of HIV samples from study patients and controls demonstrated changes in the pattern of viral mutations that differed significantly from what would be encountered naturally. The identified alterations were consistent with an effect resulting from KP-1461's proposed mechanism of action. These findings suggest that the novel antiretroviral approach illustrated by this study should be further investigated, particularly given the relatively good tolerability and the demonstrated excellent safety in this limited cohort study.

01 Aug 2011·Journal of the International Association of Physicians in AIDS Care

Safety, Tolerability, and Pharmacokinetics of KP-1461 in Phase I Clinical Studies

Article

Author: Laurent, Jean-Pierre ; Clay, Patrick G. ; McRae, MaryPeace

Background: KP-1461 is a prodrug to KP-1212. KP-1212 is a viral mutagen designed to increase viral error rate. Methods: We describe 2 phase I studies: KP1461-101 (double-blind, placebo-controlled, single, escalating doses, 100 to 1600 mg study in 42 non-HIV-infected participants) and KP-1461-102 (double-blind placebo-controlled dose escalation 14-day study in HIV-infected participants, 400-3200 mg). Primary objectives were safety/tolerability. Secondary objectives included pharmacokinetic analysis with exploratory objective to characterize KP-1212 effects on viral load. Results: KP-1461 was well tolerated. Majority of adverse events were grade 1 (neurological, gastrointestinal, cardiovascular). Four participants experienced grade 3 and 1 experienced a grade 4 event. Analysis demonstrated no difference in pharmacokinetic parameters at day 1 or 14. Linear pharmacokinetics found in 1600 mg arm. Compared to placebo, only at the 3200 mg dose demonstrated a marginally statistically significant virologic response. Conclusions: These studies provide safety/tolerability information and suggest virologic efficacy. KP-1212, a first-in-class antiretroviral, demonstrates the ability to induce viral eradication in vitro. Viral reduction in vivo may foretell a paradigm shift in HIV pharmacotherapy.

01 Jan 2009·DrugsQ1 · MEDICINE

Inhibition of Viral Polymerases by 3′-Hydroxyl Nucleosides

Q1 · MEDICINE

Review

Author: Deval, Jerome

Over the past 20 years, nucleoside analogues have constituted an arsenal of choice in the fight against HIV, hepatitis B and C viruses, and herpesviruses. Classical antiviral nucleosides such as zidovudine act as obligate chain terminators. Once incorporated as monophosphates into the viral nucleic acid, they immediately block the progression of the polymerase as a result of their lack of a reactive 3'-hydroxyl (3'-OH) group. This review explores beyond the paradigm of obligate chain termination, from a structural and a mechanistic perspective, the strategy of inhibiting viral polymerases (RNA- and DNA-dependant) with nucleoside analogues containing a 3'-OH group. Depending on their mechanism of action, these molecules typically fall into the following three categories: (i) delayed chain terminators; (ii) pseudo-obligate chain terminators; or (iii) mutagenic nucleosides. Delayed chain terminators (i.e. penciclovir, cidofovir and entecavir) block the polymerase at an internal position within the viral nucleic acid, whereas R7128 and the 4'C substituted nucleosides do not permit subsequent incorporation events. Ribavirin, 5-hydroxydeoxycytidine and KP1461 are not chain terminators. Instead, they inhibit viral replication after mispairing with the template base, resulting in random mutations that are often lethal. Finally, brivudine, clevudine and other L-nucleosides have unique or yet to be defined mechanisms of inhibition.

100 Deals associated with KP-1461

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