ImmunityBio has opened enrollment for a Phase 2 clinical trial investigating ANKTIVA (nogapendekin alfa inbakicept-pmln) as a potential treatment for long COVID, representing the first study of an IL-15 agonist immunotherapy for this challenging condition. The announcement comes as long COVID continues to affect an estimated one in five American adults who previously had COVID-19, creating a substantial public health burden with no established therapeutic options.
Novel Approach to Long COVID Treatment
The exploratory, single-arm study designated COVID-4.019-Long (NCT07123727) will evaluate ANKTIVA's safety when administered subcutaneously to participants with long COVID. The trial aims to recruit up to 40 participants who meet World Health Organization criteria for long COVID diagnosis.
"Early in the pandemic, the common assumption was SARS-CoV-2 would prove to be a transient infection, as is the case with coronaviruses in general. But we now know viral nucleic acid and proteins can be in the gut mucosa months after infection," said Dr. Patrick Soon-Shiong, Founder, Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio. "As such, an antiviral strategy looks insufficient to treat or cure long COVID."
Study Design and Objectives
The primary objective focuses on evaluating ANKTIVA's safety profile in long COVID patients, while secondary endpoints will assess the drug's effect on absolute lymphocyte count. Exploratory objectives include measuring improvements in natural killer (NK) cell and CD8+ T cell counts, as well as evaluating the immunological function of these critical immune cells.
ANKTIVA functions as a first-in-class IL-15 agonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha. This design allows the drug to bind with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells, mimicking natural biological properties of membrane-bound IL-15 receptor alpha.
Expanding Therapeutic Applications
The long COVID trial represents a significant expansion of ANKTIVA's clinical development program beyond oncology. The drug is currently FDA-approved with Bacillus Calmette-Guérin (BCG) for treating patients with BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ. Additionally, ANKTIVA is being evaluated in multiple studies for various cancers including non-small cell lung cancer, glioblastoma, non-Hodgkin lymphoma, Lynch syndrome, ovarian cancer, and HPV-associated tumors.
The company is also investigating ANKTIVA's potential in HIV and lymphopenia, demonstrating the broad therapeutic potential of IL-15 agonism across infectious diseases and immune dysfunction.
Addressing Unmet Medical Need
Long COVID presents a complex clinical challenge, encompassing more than 200 identified symptoms that can persist for weeks, months, or years after initial COVID-19 infection. Common symptoms include fatigue, brain fog, coughing, shortness of breath, heart palpitations, and changes in smell or taste. The condition can lead to chronic health conditions requiring comprehensive care and may result in disability.
Dr. Soon-Shiong explained the rationale for ANKTIVA's potential efficacy: "Based on clinical insights to date, we believe ANKTIVA may be a new therapeutic option for this chronic and potentially disabling condition by enhancing immune function, facilitating viral clearance, and addressing underlying contributions to long COVID."
Collaborative Research Efforts
ImmunityBio is conducting the study alongside a separate Phase 2 trial at the University of California – San Francisco, both supported by the company. This dual-site approach aims to accelerate patient enrollment and data collection while ensuring robust safety and efficacy evaluation.
The IL-15 cytokine plays a crucial role in immune system function by affecting the development, maintenance, and function of NK and CD8+ killer T cells. By activating these immune cells, ANKTIVA aims to overcome immune dysfunction and restore memory T cell activity, potentially addressing the persistent viral components and immune dysregulation associated with long COVID.
