Candidate: Peginterferon Lambda
Type: Late-stage, first-in-class, type III interferon (IFN) designed to stimulate immune responses critical for the development of host protection during viral infections. Lambda targets type III IFN receptors which are distinct from the type I IFN receptors targeted by IFN alfa, resulting in activation of the same Jak-STAT signal transduction cascade.
Eiger says Lambda stimulates immune responses critical to innate defenses with a mechanism of action potentially agnostic to variants of SARS-CoV-2 and resistance concerns with other treatments. If authorized, the company reasons, Lambda could be prescribed more broadly to help reduce illness severity, hospitalizations, and deaths, as well as reduce the probability of infection following exposure, among adults.
2022 Status: 60% Lower Death Risk, 50% Reduced Hospitalization Risk—Eiger on March 17 announced positive data from the Phase III TOGETHER trial (NCT04727424) showing that Peginterferon Lambda reduced the risk of COVID-19-related hospitalizations or emergency room visits greater than six hours by 50% (primary endpoint) and death by 60%. The data came from final analyses evaluating data from 1,936 patients, with 84% of patients having received at least a single dose of any COVID-19 vaccine.
After conducting viral sequencing on all patients, Eiger found that the primary endpoint was achieved across all variants tested, including Omicron. Based on the data, Eiger said, it believes Lambda has the potential to be effective against any new arising variants.
Eiger said it plans to discuss the results with FDA and submit an application for Emergency Use Authorization (EUA) “as soon as possible.”
TOGETHER was a multi-center, randomized, double-blind, placebo-controlled study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness.
2021 Status: Enrollment to Continue—Eiger said September 20 that the Data Safety Monitoring Board (DSMB) of the company’s Phase III TOGETHER platform study (NCT04727424) recommended that investigators continue enrollment of the Peginterferon Lambda arm in the study, designed to evaluate the first-in-class, type III interferon in outpatients with COVID-19. The recommendation followed an interim futility analysis based on 453 patients, randomized 1:1 active treatment to placebo. The randomized, placebo-controlled trial is assessing Peginterferon Lambda among multiple therapeutics in newly diagnosed, non-hospitalized but high-risk patients with COVID-19.
The Peginterferon Lambda arm targets enrollment of up to 800 patients at high risk for developing complications from progression of COVID-19 The TOGETHER platform study is currently recruiting at twelve sites in Brazil.
First Patient Dosed—Eiger said July 6 that the first patients were dosed with Peginterferon Lambda (Lambda) in the Phase 3 TOGETHER platform study in outpatients with COVID-19. Lambda is administered as a one-time, subcutaneous dose.
TOGETHER is a multi-center, investigator-sponsored, randomized, placebo-controlled Phase 3 study evaluating multiple therapeutics in newly diagnosed, outpatients with COVID-19. The primary endpoint is a clinical outcome comparing emergency room visits and/or hospitalization in each active arm versus placebo. Each arm targets enrollment of up to 800 patients at high risk for developing complications from progression of COVID-19, with planned interim analyses for futility.
Peginterferon Lambda Added—Eiger said May 3 that a single subcutaneous dose of Peginterferon Lambda will be added to the ongoing, multi-center, Phase 3 TOGETHER platform study (NCT04727424) assessing the first-in-class, type III interferon in outpatients with COVID-19.
The TOGETHER trial’s primary endpoint is a clinical outcome comparing emergency room visits and/or hospitalization in each active arm versus placebo. Each arm targets enrollment of up to 800 patients at high risk for developing complications from progression of COVID-19, with planned interim analyses for futility in each arm.
2020 Status: Mount Sinai said June 18 it had launched a Phase II randomized clinical trial designed to evaluate Lambda in hospitalized COVID-19 patients receiving supplemental oxygen.
The trial is expected to recruit 66 patients who will receive an injection of Lambda under their skin as a single, one-time dose. Mount Sinai said its researchers believe Lambda can help the immune system control the virus infection, decreasing the duration and severity of COVID-19. The trial’s principal investigator is Thomas Marron, MD, PhD, assistant director of Early Phase and Immunotherapy Clinical Trials at The Tisch Cancer Institute at Mount Sinai.
Scott Friedman, MD, Dean for Therapeutic Discovery at the Icahn School of Medicine at Mount Sinai, contacted Lambda maker Eiger Biopharmaceuticals, which agreed to donate the drug for the trial.
Eiger and Friedman received a $500,000 donation from the COVID-19 Early Treatment Fund started by Silicon Valley entrepreneur and philanthropist Steve Kirsch, who in turn found matching funds from donors that include Corrigan Walla Foundation and David Baszucki, the founder and CEO of Roblox Corporation, and his wife, author Jan Ellison Baszucki.
In April, Eiger said the first patients were dosed in a Phase II study of Lambda in outpatients with mild COVID-19 at the Stanford University School of Medicine. Approximately 120 patients were to be randomized 1:1 to a single subcutaneous dose of Lambda or normal saline placebo to evaluate the efficacy of Lambda in reducing the duration of viral shedding of SARS-CoV-2 virus and in reducing duration of symptoms and hospitalization in patients with mild COVID-19. Patients were to be followed for 28 days.
COVID-19: 300 Candidates and Counting
To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: