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Phase 3 Study to Examine Humanized Monoclonal Antibody as COVID-19 Treatment

April 15, 2021

By Julie Gould 

Richard Miller, MD, board-certified oncologist and adjunct clinical professor of Medicine (oncology) at Stanford University Medical CenterRichard Miller, MD, board-certified oncologist and adjunct clinical professor of Medicine (oncology) at Stanford University Medical Center, discusses a trial examining the use of CPI-006, a humanized monoclonal antibody that is designed to bind to and activate B cells, for the treatment of infectious diseases, including COVID-19. 

What existing data led you and your co-investigators to conduct this research?

Based on our experience with the biology of B cells and development of rituximab and ibrutinib, we set out to design an antibody that activates B cells into antibody producing cells that secrete antigen specific antibodies. The antibody, CPI-006, was shown to activate B cells in vitro leading to differentiation into plasma cells and memory B cells. CPI-006 is in an ongoing Phase 1 study in cancer where we have shown that it is well tolerated and does induce the activation of B cells in patients. We presented this data in an oral presentation at the American Society of Clinical Oncology (ASCO) annual meeting in 2019.  

Interestingly, early on in the pandemic we also happened to treat a patient in our Phase 1 cancer study that was diagnosed with concomitant asymptomatic COVID-19 on routine screening at the time of initiating CPI-006 therapy. The patient was in a very high-risk group for progression of COVID-19 due to her age, race, and comorbidities such as chronic obstructive pulmonary disease, cancer, and extensive prior treatment with chemotherapies. The patient remained asymptomatic from COVID-19 following treatment with CPI-006 and we observed exactly what we would expect in terms generating increased levels of antibodies and memory B cells. For example, the patient in our study generated IgG and IgM antibody levels at the high end of the range seen in samples from recovered COVID-19 patients that had more favorable baseline characteristics (younger with no comorbidities). Based on the known mechanism of action of CPI-006, which induces active immunization, data from our cancer study and the observation in a COVID-19 patient, we felt there was evidence to study CPI-006 in COVID-19, which was confirmed with the positive results in our Phase 1 COVID-19 study that was recently completed.

Please briefly describe your study and its findings. Were any of the outcomes particularly surprising? 

In the CPI-006 COVID-19 Phase 1 study, we treated 29 patients with mild-to-moderate COVID-19 symptoms that required hospitalization, giving increasing single doses of CPI-006 in successive cohorts. The results were very encouraging. None of the patients in the study progressed to needing mechanical ventilation, despite all having comorbidities or other high-risk factors for adverse outcomes. For a point of reference, recent literature shows that about 20% of patients with moderate COVID-19 disease will progress to requiring invasive mechanical ventilation. All of the patients in the study were released from the hospital with a median time to discharge of 3 days; 79% discharged from the hospital by day 7. 

The biomarker data from the study also confirmed the mechanism and results we saw in our cancer study —CPI-006—treated patients appear to generate higher, more sustained titers of antibodies, and importantly these antibodies are polyclonal, meaning they are a diverse set of antibodies recognizing binding sites along the entire length of the spike protein and other protein components of the virus. This polyclonal response would be expected to provide protection against the emergence of viral variants. To explore this, we tested the antibodies from two patients in our study against the subsequently emergent UK and South African variants and found they neutralized these new strains.  

What are the possible real-world applications of these findings in clinical practice?

Based on the results to-date, we believe CPI-006 provides an elegant and practical solution to many of the potential issues with current COVID-19 therapies, vaccines and the problem of viral mutation. The potential advantages of CPI-006 are that it is designed to 1) enhance the generation of polyclonal anti-SARS-CoV-2 antibodies to any viral variant; 2) improve long-term immunity and provide protection from reinfection; 3) accelerate viral clearance and reduce the risk of spreading; and 4) increase cross protection to mutants of SARS-CoV-2 and other coronaviruses. In real-world use, we expect this would help keep patients off mechanical ventilation and get them out of the hospital sooner, with less risk of future reinfection. 

In addition, CPI-006’s proposed dose is much lower than passive monoclonal antibody therapies, allowing it to be delivered in a short 10-minute infusion time, with less pressure on supply, and the longer term potential to transition to a more convenient subcutaneous administration. More broadly beyond COVID-19, it has the potential to be a foundational therapy for treatment or prevention of other infectious diseases.  

Do you and your co-investigators intend to expand upon this research? 

Our current focus is executing on our randomized double blind Phase 3 study, which is expected to enroll approximately 1,000 hospitalized COVID-19 patients at sites in North America, Europe, South Africa and Latin America. Enrollment in the study is expected to be complete in the fourth quarter 2021. If positive, we will work to make CPI-006 available as soon as possible to COVID-19 patients, and longer-term, we would consider expanding our research into broader applications for COVID-19 and other infectious diseases. In addition, we also have the potential to continue studying CPI-006 for the treatment of patients with various cancers. Given CPI-006’s mechanism of action, we believe that this could be a valuable therapeutic ready for future pandemics. 

Is there anything else pertaining to your research and findings that you would like to add? 

We are proud to be part of the global community of scientists working to address the significant impact of COVID-19. There has been phenomenal progress in a short period of time, but unfortunately, we expect that COVID-19 will remain a major health problem for years, likely associated with endemic and epidemic outbreaks. Based on the results to-date, we believe CPI-006 has the potential to be a novel immunotherapy for the treatment of COVID-19 and other infectious diseases. Its mechanism of action is unlike any other therapies approved or being studied for COVID-19 that we are aware of – stimulating the body's adaptive immune response to increase levels of anti-SARS-CoV-2 antibodies and memory B cells.  

About Dr Miller 

I am Richard A. Miller, a board-certified oncologist and Adjunct Clinical Professor of Medicine (oncology) at Stanford University Medical Center. Over the years, I have co-founded and led several biotech companies, including Corvus Pharmaceuticals, where I currently serve as president & Chief Executive Officer. I also currently serve as Chairman of the Board and interim Chief Executive Officer of Angel Pharmaceuticals, a new China-based biopharmaceutical company that is developing Corvus’ pipeline in Asia.

Prior to Corvus, I was co-founder and chief executive officer of Pharmacyclics (acquired by AbbVie), where we developed Imbruvica (ibrutinib). Prior to that, I was a co-founder, Vice President and Director of IDEC (which merged to form Biogen IDEC, now Biogen), where we developed Rituxan (rituximab). Imbruvica and Rituxan are highly successful medicines that have been administered to millions of patients with lymphomas and autoimmune diseases.

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