It’s a nail-biting time for UK-based biotech Verona Pharma plc. Over 15 years since its founding, Verona will soon deliver results of a second Phase III trial of chronic obstructive pulmonary disease (COPD) hopeful ensifentrine. If it replicates the strongly positive efficacy and safety data seen in a first study, the company has a blockbuster in its hands, according to analysts. If not, Verona's survival may be at stake.
This binary outlook is typical for an asset-focused biotech. What’s less ordinary about Nasdaq-listed Verona is that it’s gearing up to compete in a huge, Big Pharma-dominated field where diagnosis can be tricky, generics are arriving fast, and where many specialists stick to products they know, and those covered by insurers
Trial Population May Be Double Edged Sword
Verona’s broad trial population could expand ensifentrine’s target market – or reduce its chances of being approved at all. Since almost half of patients in the Enhance trials are not taking any maintenance therapy, only a few are on a LAMA or LABA and ICS and none are on triple combination treatments, the trials “don’t fully capture how [ensifentrine] is likely to be used in the real-world clinical setting,” cautions Jefferies’ analyst Suji Jeong. That real-world setting will, initially at least, include patients failing the widely prescribed triple therapies.
Verona didn’t want to limit its drug to post-triple therapy, but also knew it would be harder to show additional benefit in this setting. A short Phase 2 trial in 2019 pitted ensifentrine against Boehringer Ingelheim’s LABA/LAMA combo Stiolto Respimat (tiotropium/olodaterol), with about 40% of the 79 patients also on an ICS – in other words, on triple therapy. The drug failed to significantly improve FEV1, though it did show numerical improvement. There were also trial design challenges that may have under-played ensifentrine’s benefits.
With its longest registrational trial lasting less than a year, Verona is already at the bare minimum when it comes to meeting long-term safety follow-up for a widespread condition such as COPD, say analysts. Furthermore, FDA’s division of pulmonary, allergy and critical care (DPACC) can be “very conservative and difficult,” warns respiratory specialist Jim Donohue, who has been involved in several respiratory drug submissions
