Companies Collaborate to Develop Companion Diagnostic for Immunotherapy in HPV-Associated Cervical Dysplasia

QIAGEN and INOVIO Pharmaceuticals, Inc. are extending their collaborative efforts with a new agreement to develop liquid biopsy–based companion diagnostic assays for INOVIO agents, according to a news release from INOVIO.¹

The focus will center on co-developing a companion diagnostic test that can inform which women with advanced human papillomavirus (HPV)–associated cervical dysplasia are likely to benefit from VGX-3100, an investigational immunotherapy.

The diagnostic platform will be developed for use on the Illumina NextSeqTM 550Dx instrument, which allows for next-generation sequencing CE-in vitro diagnostic testing, among other features.²

The goal of the collaboration is to utilize QIAGEN’s bioinformatic expertise to further the predictive power of the preliminary biomarker signature developed by INOVIO.

“As we advance our DNA medicines platform, we are always looking for ways to drive innovation with our own technology or that of a creative and accomplished partner. QIAGEN is contributing an extensive track record of developing and commercializing novel diagnostic tests,” said president, CEO, and director of INOVIO, J. Joseph Kim, PhD.¹ “INOVIO is developing VGX-3100 as a nonsurgical treatment for cervical pre-cancer, and pre-treatment biomarkers we have discovered could be a targeted way to identify patients most likely to respond to treatment. The goal is to increase the absolute efficacy of the immunotherapy.”

VGX-3100 is a DNA-based medicine that utilizes the patient’s immune system to clear HPV-16/18–associated high-grade precancerous lesions. The agent is being developed for use in anal and vulvar dysplasia, in addition to cervical dysplasia, where it is in late stages of development and is being evaluated in 2 prospective, randomized, phase 3 clinical trials.

The REVEAL 1 trial (NCT03185013) is investigating the efficacy and safety of the immunotherapeutic agent followed by electroporation (n = 131) vs placebo (n = 62) in women with HPV-16/18–associated cervical high-grade squamous intraepithelial lesions (HSIL). The study utilizes INOVIO’s CELLECTRA® 5PSP device.³

INOVIO announced that the REVEAL 1 study met its primary end point for efficacy among all evaluable patients (n = 193); 23.7% of patients treated with the VGX-3100 regimen had histopathological regression of HSIL and virologic clearance of HPV-16 and/or HPV-18 at 36 weeks vs 11.3% of patients treated with placebo (95% CI, 0.4%-22.5%; P = .022).⁴

The study also met all secondary end points other than regression of cervical HSIL alone, which demonstrated a statistically insignificant difference of 12.8% between arms (95% CI, -0.6%-24.5%). However, patient withdrawals and loss of follow-up may have accounted for the missed end point.

Additionally, VGX-3100 was found to be well tolerated, and most adverse effects resolved without the need for medication intervention.

“There is a very significant need for a non-surgical therapeutic for young women suffering from HPV-associated cervical dysplasia. These results are very encouraging and show that we are headed in the right direction,” said principal coordinating investigator Mark H. Einstein, MD, MS, professor and chair of OB/GYN and Women’s Health in the Department of Obstetrics, Gynecology, and Reproductive Health at Rutgers New Jersey Medical School.

The second study, REVEAL 2 (NCT03721978), is currently enrolling and also evaluating VGX-3100 followed by electroporation vs placebo in patients with cervical HSIL.⁵

“We are pleased to support INOVIO by developing companion diagnostics to identify patients who would benefit from VGX-3100. Our experience in developing liquid biopsy–based diagnostic solutions for precision medicine in immuno-oncology will help INOVIO address a larger unmet medical need,” concluded Jean-Pascal Viola, senior vice president, head of the Molecular Diagnostics Business Area, and leader of Corporate Business Development, Intellectual Property, and Litigation at QIAGEN.¹

References

1. INOVIO and QIAGEN expand collaboration to develop next generation sequencing (NGS) companion diagnostic for INOVIO's VGX-3100 for advanced cervical dysplasia. News release. INOVIO Pharmaceuticals, Inc. Published February 24, 2021. Accessed March 16, 2021. http://prn.to/2NlLyVK.
2. NextSeq 550Dx instrument. Illumina. 2021. Accessed March 16, 2021. http://bit.ly/3eGHnPL.
3. REVEAL 1 (evaluation of VGX-3100 and electroporation for the treatment of cervical HSIL) (REVEAL 1). ClinicalTrials.gov. Posted June 14, 2017. Updated March 9, 2021. Accessed March 16, 2021. https://clinicaltrials.gov/ct2/show/NCT03185013.
4. INOVIO announces positive results from REVEAL 1, a phase 3 pivotal trial evaluating VGX-3100, its DNA-based HPV immunotherapy for the treatment of high-grade precancerous cervical dysplasia caused by HPV-16 and/or HPV-18. News release. INOVIO Pharmaceuticals, Inc. Published March 1, 2021. Accessed March 16, 2021. http://prn.to/3eLkAC7.
5. REVEAL 2 trial (evaluation of VGX-3100 and electroporation for the treatment of cervical HSIL). ClinicalTrials.gov. Posted October 26, 2018. Updated March 9, 2021. Accessed March 16, 2021. https://clinicaltrials.gov/ct2/show/NCT03721978.