Hope, or a new emotion for Verona investors

Having endured years of suffering, investors in the UK biotech minnow Verona Pharma will today be hoping to have caught a break: the company’s lead asset, RPL554, has apparently shown an efficacy benefit in a small pharmacokinetic study in cystic fibrosis.

The result is significant because it provides further evidence of RPL554’s safety relative to the similarly acting Daliresp and it could help with the project’s lack of market exclusivity, though the efficacy data lose their lustre on closer inspection. A 400-patient study in COPD – RPL54’s main potential use – in the second quarter remains Verona’s most important 2018 catalyst.

The current RPL554 clinical programme was made possible by a surprising $150m fundraising Verona closed last year. If the COPD study reads out positively two further COPD trials in 550 subjects should start this year, in addition to a 100-patient cystic fibrosis test (Interview – Verona investors still holding their breath, July 26, 2017).


This is not to say that Verona will turn things around overnight. Part of the problem of RPL554’s interminably slow development is that it has resulted in virtually no remaining patent life; Berenberg analysts say the molecule’s composition of matter patent expires in 2020.

Still, to have given Verona $150m investors must surely have been persuaded by other forms of IP; various patents relating to polymorphs, salts, combinations and formulations cover RPL554 into the 2030s, and there is the possibility of US orphan drug status, which would bring seven years’ market exclusivity.

This is where today’s readout could come in handy, since cystic fibrosis qualifies as an orphan condition. However, the data are far from unequivocal, and Verona is providing little detail about the 10-patient pharmacokinetic/pharmacodynamic trial in question.

It has reported a “six percent sustained improvement from baseline in FEV1”, later clarifying to EP Vantage that this was indeed a 6% relative change, presumably for both active doses combined. However, it is not revealing what the underlying FEV1 numbers were for the trial’s three arms – 1.5mg and 6.0mg doses and placebo.

On the face of it, of course, a 6% increase from baseline would compare favourably against large cystic fibrosis studies of Vertex’s Kalydeco and Orkambi, which elicited initial increases of 10 and two points in their specific genetic settings. Verona says its study enrolled subjects with a variety of genotype mutations.

However, a major red flag over the result is that Verona will not, for now, reveal how well placebo recipients did. It has provided p values for the 1.5mg and 6.0mg doses that it claims were statistically significant, but on further questioning it revealed: “This is from baseline.”

It is not immediately clear how or why the group would have performed a statistical analysis within groups, but without adjusting for placebo the efficacy result loses much of its relevance. The lower dose elicited a result with a lower p value than the higher one did, though in a trial this small it would be harsh to claim that this implies lack of a dose response.


RPL554 inhibits PDE4 as well as PDE3. Use in cystic fibrosis is based on its activity against neutrophils, which cause inflammation in lungs, as well as – Verona claims – stimulation of the CFTR ion channel in epithelial cells lining the airways.

PDE4 inhibition is, of course, more commonly used against COPD, and is the mechanism behind Astrazeneca’s Daliresp. But use of this drug has been hampered by gastro-intestinal side effects that Verona maintains RPL554 does not have; the cystic fibrosis trial produced good tolerability in line with previous studies, it said.

Verona's stock rose 19% today, and might continue to rise into the COPD readout. Cystic fibrosis could give investors something else to look forward to after years of pain, though they first need to see more robust data.

This is an updated version of a story that appeared earlier.

To contact the writer of this story email Jacob Plieth in London at [email protected] or follow @JacobPlieth on Twitter

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