(CNSNews.com) — The National Institutes of Health has selected Humanigen’s lenzilumab (aka “lenz”) for its Big Effect Trial (BET), which is being sponsored by the National Institute of Allergy and Infectious Diseases (NIAD) to help move potential COVID-19 treatments and therapies past the testing phase to being used on coronavirus patients.
Lenzilumab is a potential coronavirus therapy, not a vaccine. While a vaccine is given to individuals (usually through an injection) to build up an immune response to a specific illness or disease, a therapy is given to individuals who already have an illness or disease.
A therapy drug is used to help with the recovery process, lessen symptoms or can be given as compassionate use to someone who is suffering due to the disease they have contracted.
Humanigen, Inc. is a “clinical-stage biopharmaceutical company” whose main focus is to develop new and improved cancer treatments, specifically using lenzilumab to prevent or treat cytokine storm.
Lenzilumab is a monoclonal antibody or biologic. A monoclonal antibody is a substitute or imitation of the body’s natural antibodies which fight diseases or infections. This substitute antibody can “restore, enhance, or mimic” the immune system’s fight against infections, therefore aiding the body in its fight against coronavirus, the Mayo Clinic explained.
Because lenzilumab is a monoclonal antibody, it can block the immune signaling protein granulocyte macrophage-colony stimulating factor (GM-CSF). GM-CSF has been shown to cause cytokine storm, a COVID-19 side effect that has been fatal in many patients. Lenzilumab’s blocking of GM-CSF helps prevent cytokine storm.
Cytokine storm is “a severe immune reaction in which the body releases too many cytokines into the blood too quickly,” according to cancer.gov. Cytokines (proteins released by cells) are normally good as they help fight off infection, but if too many are released at once it is extremely harmful. It often leads to multiple organ failure and death.
“We have been studying cytokine storm in other areas than COVID-19 for 3 years,” Humanigen Chairman and CEO Cameron Durrant told CNS News.
On June 15, Humanigen issued a press release that detailed lenzilumab’s results after a Mayo Clinic study. The patients who received lenzilumab were high-risk and 33% were in the ICU prior to receiving lenzilumab. The patients treated with lenzilumab had a median recovery time of five days and had no adverse side effects.
"When treated with the company's anti-GM-CSF antibody, lenzilumab, 12 hospitalized patients with severe or critical pneumonia as a result of COVID-19 showed 'rapid clinical improvement,'" reported BioWorld in June. "Median time to recovery and discharge for the group was five days."
When compared to remdesivir (another COVID-19 treatment that has received emergency use authorization from FDA), patients were released from the hospital five days faster when using lenzilumab. Humanigen is continuing to study lenzilumab in a large Phase 3 study across 17 hospitals in the United States.
“Lenz is one of the few Phase 3 treatment options in development for COVID-19 and has the potential to be a leading treatment to prevent serious and potentially fatal outcomes in high risk patients who are hospitalized with COVID-19,” Durrant said.
On July 27, Humanigen announced that lenzilumab had been selected by NIAID for the Big Effect Trial (BET). Lenzilumab will be tested in combination with remdesivir in 200 COVID-19 patients compared to remdesivir alone. This trial will build on the initial NIAID trial that led to the emergency use authorization of remedesivir, which remains one of the few available treatment options for COVID-19.
The BET will be a big stepping-stone as the team at Humanigen works to get lenzilumab approved for use and will answer the scientific question of whether targeting the virus directly with remdesivir will work synergistically with lenzilumab that targets the overactive immune response.
“We believe that LENZ’s mechanism of action as an immunomodulator could work very nicely with remdesivir as well as other potentially direct-acting antivirals, including convalescent plasma to intervene in hospitalized patients that are on standard of care,” Durrant said.
Lenzilumab is now one of only four therapeutics to be selected by the NIH for study in COVID-19 and marks a significant achievement for Humanigen.
“The NIH is arguably the world’s foremost government-supported research organization for public health, so we’re thrilled that lenzilumab was selected as one of the BET high-priority therapeutic candidates for evaluation,” Durrant said. “This important trial will help advance NIAID’s strategic plan for COVID-19 research.”
“In addition to its inclusion in the NIH Big Effect Trial (BET), lenzilumab is one of the few treatment options that has advanced to a Phase 3 for COVID-19. We believe lenzilumab has the potential to become a leading treatment to prevent serious and potentially fatal outcomes in high-risk patients who are hospitalized with COVID-19,” stated Durrant.
Humanigen’s Phase 3 trial is expected to be completed this year and lenzilumab may be an available treatment option this coming winter if the data support approval.
Although there has been a focus on development of vaccines to end the COVID-19 pandemic, therapeutics such as lenzilumab offer near-term treatment options that can change the arch of the pandemic by significantly reducing the severity of the disease and its potential mortality.
“While large companies focused on vaccines continue to dominate the news, we all need to be in agreement that we cannot place all of our eggs in one basket. We need a variety of medical and social interventions to stop the onslaught of COVID-19,” Durrant said. “Defeating this pandemic will take a multi-pronged approach, and therapeutics will be an important part of an overall solution…”
Therapeutic options may also provide a more achievable goal in terms of necessary manufacturing scale. Lenzilumab would only target hospitalized severe patients, which are projected to be a few hundred thousand patients this winter, versus the difficult task of trying to manufacture and vaccinate the entire population, assuming there is a safe and effective vaccine.
“As we continue to pursue vaccine development, we must also look toward the shorter-term, more achievable goal of delivering effective treatments for hospitalized COVID-19 patients and invest significantly greater resources toward their development,” Durrant finished.
(Disclosure: the chief scientific officer of Humanigen, Dale Chappell, is the uncle of CNS News reporter Bailey Duran.)