Inovio’s decision two years ago to pivot away from some therapeutic cancer vaccines looked sensible – the problem now might be the other vaccine projects it pivoted to.
Data released yesterday on the group’s lead asset, VGX-3100, raise questions about whether this therapy is approvable, let alone commercially viable, and the group’s shares opened down 8% this morning.
VGX-3100 is a DNA vaccine designed to treat HPV-associated cervical high-grade squamous intraepithelial lesions, which are precancerous cervical cells that can, but do not always, progress to cervical cancer. The current standard is surgical removal of the affected cells, but this comes with a risk of complications during future pregnancies.
Inovio hopes that VGX-3100 will become an alternative to surgery; however, the latest data, from the phase III Reveal 1 study, are far from convincing. The company claimed a win here but admitted that the trial only met its primary endpoint when using a modified intent-to-treat analysis that excluded eight patients without endpoint data.
In the more stringent intent-to-treat population, which counted those patients as non-responders, VGX-3100’s statistically significant benefit disappeared.
The question now is whether the result in the mITT population will be enough for approval, and until a filing is made it is not known whether the FDA will accept this.
Even assuming that the agency will be lenient, response rates with VGX-3100 do not look too impressive compared with surgery. Even in the mITT population only 24% of 131 patients in the treatment group responded, versus 11% of 62 in the placebo group. Success rates of around 75% have been reported with the most common surgical technique, large loop excision of the transformation zone.
Inovio is already trying to improve response rates, and to this end is working with Qiagen on a companion diagnostic to identify women most likely to benefit from VGX-3100. A post-hoc analysis of the project’s phase II trial found that the test predicted response in 85% of patients.
Still, this needs to be proved prospectively, and this is what Inovio aims to do in VGX-3100’s second pivotal study, Reveal 2. But this trial’s enrolment was hit by the coronavirus pandemic, and the company is not saying when it will be completed.
The pressure is now on Reveal 2 to deliver, and Inovio’s efforts to develop a biomarker will also be “critical to any commercialisation strategy”, Stifel analysts noted. Sellside consensus puts VGX-3100’s 2026 sales at $400m, according to EvaluatePharma.
If VGX-3100 turns out to be another dud, Inovio's Covid-19 vaccine candidate INO-4800 looks unlikely to save the company. The pivotal portion of that project’s phase II/III trial is still on clinical hold, and the group does not expect to start enrolling patients until late in the second quarter, by which time existing vaccines should be making a dent in Covid-19 infections.