dm+d

Unassigned

New Medicines

Cervical dysplasia caused by human papillomavirus (HPV) types 16 and 18

Information

New molecular entity
Inovio
Inovio

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Nov 21Inovio is advancing its partnership with Qiagen to co-develop an in-vitro diagnostic tool based on a bio-marker to guide clinical decision-making for the use of VGX-3100 in cervical HSIL [12].
Nov 20Completion of PIII REVEAL 1 data collection for VGX-3100 has been impacted by the recent pandemic surge; data readout for primary CIN PIII trial is expected in H1 21 [6].
Nov 19No plans for EU development discussed in latest company quarterly report [5].
Jun 19Inovio Pharmaceuticals plans to submit a BLA to the US FDA in 2021 [4].
May 19Inovio Pharmaceuticals announces that bizalimogene ralaplasmid was granted an advanced therapy medicinal product certificate for quality and non-clinical data by the EMA [4].

Category

DNA-based immunotherapy. It is comprised of two DNA plasmids targeting the E6 and E7 proteins of HPV types 16 and 18. These plasmids are named mavilimogene ralaplasmid and bizalimogene ralaplasmid, for HPV 16 and 18, respectively.
Cervical cancer is the third most commonly diagnosed cancer worldwide and the fourth leading cause of cancer death in women. Cervical cancer causes around 266,000 deaths worldwide commonly in those in their 20s and 30s [2].
Cervical dysplasia caused by human papillomavirus (HPV) types 16 and 18
Intramuscular

Trial or other data

Nov 21INOVIO has completed follow-up of subjects in REVEAL 1 and expects to present its findings later this year. REVEAL 2 is on track to complete enrolment of 198 adult women with histologically confirmed cervical HSIL before year end [12].
Jul 21PIII REVEAL 2 study is now due to complete collection of primary outcome data in Jul 22 [11].
Mar 21Inovio will continue to follow subjects in the REVEAL1 trial for safety and durability of response for 18 months following the last administration. Enrolment for the confirmatory REVEAL 2 trial is ongoing [10].
Mar 21In PIII trial REVEAL-1 the primary endpoint of histopathological regression of HSIL combined with virologic clearance of HPV-16 and/or HPV-18 at week 36 was met with 23.7% (31/131) in the VGX-3100 group versus 11.3% (7/62) in the placebo group (p=0.022; 95%CI: 0.4,22.5). All secondary efficacy endpoints were achieved [9].
Jan 21Positive data from open-label PII trial (NCT03180684) showing efficacy in treatment of HPV-16 and HPV-18-associated vulvar dysplasia in 24 women aged 22-70. A ≥ 25% reduction in HPV-16/18-associated vulvar HSIL (high-grade squamous intraepithelial lesion) was observed for 63% of VGX-3100 pts (12 of 19) 6 months post-treatment. Of 20 pts with histology data, 15% resolved their vulvar HSIL and had no HPVp-16/18 virus detectable in the healed area (vs. 2% estimated as having spontaneous resolution of vulvar HSIL caused by HPV-16/18). VGX-3100 was safe and well-tolerated. Mild-to-moderate injection site pain was the most common side effect. No cases of vulvar cancer have been observed in the trial.[8]
Nov 20Collection of primary outcome data in PIII REVEAL 1 study (NCT03721978) finished in Jul 20. PIII REVEAL 2 study (NCT037219780 is recruiting and expects to complete collection of primary outcome data in Apr 21 [7].
Jan 20The pivotal PIII REVEAL programme (randomized evaluation of bizalimogene ralaplasmid and electroporation for the treatment of cervical HSIL) will treat cervical dysplasia caused by human papillomavirus (HPV) 16/18 and includes the primary REVEAL 1 study and the confirmatory REVEAL 2 study, being conducted in parallel, as per FDA general guidance [4].
Dec 19PIII REVEAL 1 study (NCT03185013) is no longer recruiting; collection of primary outcome data is due to complete Apr 20 [3].
Dec 19PIII REVEAL 1 study (NCT03721978) is recruiting; collection of primary outcome data is due to complete Apr 21 [3].
Mar 19PIII REVEAL studies´ primary endpoint is regression of cervical HSIL AND virologic clearance of HPV-16 and/or HPV-18 in the cervix. They will evaluate cervical tissue changes at approximately 9 months after a three dose regimen of VGX-3100 administered at months 0, 1, and 3. Secondary endpoints include safety, tolerability, regression of CIN 2/3 to CIN 1 or normal, virologic clearance of HPV, efficacy measured by non-progression to cancer and clearance of HPV from non-cervical anatomic locations [1].