COVID-19 Cell Therapy Shows Promise in Proof-of-Concept Clinical Trial

Tevogen Bio’s TVGN 489, an investigational allogeneic CD8+ T-cell therapy intended to treat patients with COVID-19 with acute high-risk disease, has demonstrated safety and met efficacy end points in a phase 1, proof-of-concept (POC) clinical trial (NCT04765449).¹

TVGN 489 consists of cytotoxic T lymphocytes derived from healthy volunteers who have recovered from COVD-19. The cells are manufactured to target multiple proteins across the SARS-CoV-2 genome that are preserved regardless of variant; the cell therapy is not limited to targeting the spike protein, which is the target of current vaccines and monoclonal antibodies.² A recent review carried out by the company suggested that the therapy “is expected to retain activity against recent variants, including XBB and BQ and its subtypes, which appear to have the ability to evade some existing prophylactic options and immunity.”³

The trial, which completed dosing of patients last summer, compared results from 12 patients who received TVGN 489 to 18 patients enrolled in the study’s observational arm, who received standard of care treatment for COVID-19.^1,2 It was noted that no patients who received TVGN 489 showed progression of their COVID-19 infections and that none of these patients experienced reinfection with COVID-19 or long COVID during 6 months of follow-up. All patients treated with TVGN 489 returned to their baseline level of health by 14 days post-treatment. Furthermore, patients treated with TVGN 489 showed disease symptom relief in a rapid, consistent time frame, while patients treated with the standard of care demonstrated improvement in a less consistent and sometimes longer time frame. The study additionally met its secondary end points for reductions in viral load and post-treatment presence of cellular and humoral anti-COVID-19 responses.

In terms of safety, no dose-limiting toxicities occurred in the 12 patients treated with TVGN 489 and these patients experienced no cases of grade 3 or higher infusion reactions, grade 2 or higher cytokine release syndrome (CRS), grade 2 or higher neurotoxicity, or graft versus host disease. There were no grade 4 or higher adverse events (AEs) determined to be related to the cell therapy and outside the scope of identified COVID-19-related AEs.

“I’m greatly encouraged by the POC trial experience of TVGN 489 and hopeful that our investigational COVID-19 therapy will eventually offer hope to a substantial segment of patients,” Neal Flomenberg, MD, chief scientific officer, Tevogen Bio, said in a statement regarding the news.¹

Patients in both the treatment arm and the observational arm were ambulatory, had a newly diagnosed COVID-19 infection, and were higher risk for COVID-19-related complications from advanced age, heart disease, lung disease, liver disease, kidney disease, hypertension, diabetes, cancer, or obesity. In order to receive treatment with TVGN 489, patients were required to have a matching human leukocyte antigen (HLA) with the cells. Patients that did not have the matching HLA were able to participate in the observational arm. It was noted that 50% of the patients in the treatment arm were immunocompromised, while only 6% of those in the observational arm were immunocompromised. The immunocompromised status of the treated patients was related to prior treatment for cancer or autoimmune disease. It was additionally noted that the treatment arm included patients infected with “a variety of COVID variants ranging from Delta through Omicron BA.5.2.” The number of comorbidities in the treated patients ranged from 2 to 5.

The trial was open to patients aged 18 years and older. Patients requiring supplemental oxygen, those showing evidence of active COVID-19-related CRS according to study-specific criteria, those with a corrected QT interval greater than 450 milliseconds, and those receiving concomitant treatment with another experimental intervention for COVID-19 other than Remdesivir were excluded from the study. Additional exclusion criteria related to patient health status, current treatments, and treatment history. The study was carried out at Thomas Jefferson University.

Tevogen Bio expects that the data from the trial will be submitted for publication in a peer-reviewed journal in the coming weeks. In December 2022, the company announced that it will pursue a new clinical trial for TVGN 489 specifically focused on evaluating the therapy’s efficacy in patients who are immunocompromised.³

“The highly encouraging data of TVGN 489 allows us to turn our attention to the critical unmet need in the COVID-19 landscape,” Dolores Grosso, DNP, principal investigator of the trial, added to the statement.¹ “Immunocompromised and the elderly and infirm usually do not benefit from currently available prevention or treatment strategies for COVID-19 and remain highly vulnerable to poor outcomes with a COVID-19 infection. These patients, as well as those individuals with long COVID, urgently require new treatment options.”

REFERENCES

1. Tevogen Bio announces positive proof-of-concept clinical trial results of its off-the-shelf, allogeneic cytotoxic CD8+ T-cell therapy for treatment of acute high-risk COVID patients, first clinical product of company’s precision cell therapy platform. News release. Tevogen Bio. January 23, 2023. Accessed January 23, 2023. https://tevogen.com/press_release/tevogen-bio-announces-positive-proof-of-concept-clinical-trial-results/ 

2. Tevogen Bio Announces Positive Safety Results Upon Completion of Patient Enrollment in Proof-of-Concept Clinical Trial of T cell Therapy for Elderly or High-Risk COVID-19 Patients. News release. Tevogen Bio. August 1, 2022. Accessed January 23, 2023. https://tevogen.com/press_release/tevogen-bio-announces-positive-safety-results-upon-completion-of-patient-enrollment/ 

3. TevogenBio to study its investigational COVID-19 T cell therapy in immunocompromised patients who are unable to benefit from currently available prevention or treatment options. News release. Tevogen Bio. December 7, 2022. Accessed January 23, 2023. https://tevogen.com/press_release/tevogen-bio-to-study-its-investigational-covid-19-t-cell-therapy-in-immunocompromised-patients-who-are-unable-to-benefit-from-currently-available-prevention-or-treatment-options/