Vectura to take big financial hit as VR475 fails to meed endpoint

Vectura Group announced on Monday that its phase III study of VR475 in adult and adolescent patients with severe uncontrolled asthma did not meet its primary endpoint.

The London-listed firm described VR475 as a drug-device combination, consisting of budesonide delivered by its proprietary nebuliser inhalation system.

Top-line results indicated a trend in the reduction of the annualised rate of clinically significant exacerbations among patients receiving either VR475 1mg or VR475 0.5mg doses twice daily during a 52-week treatment period compared to placebo, but the results did not reach statistical significance.

The open label arm with conventional nebuliser also failed to reach statistical significance compared to placebo.

Vectura said available safety data for VR475 was consistent with the known profile of inhaled budesonide.

Based on those results, the firm said it had decided not to further pursue the development and partnering of VR475.

The company would complete the full analysis of the primary and secondary data, and intended to present the complete study results at an upcoming medical conference and seek to have the data published in a peer-reviewed journal.

It said an initial review of the available secondary endpoints and the safety data showed certain endpoints achieving statistically significant and clinically meaningful differences between VR475 and placebo, and compared to conventionally nebulised budesonide.

Those results reinforce the differential characteristics of Vectura’s guided inhalation system versus conventional nebulisation, the board explained, as well as confidence in the ongoing VR647 programme and three additional early stage nebulisation programmes, using non- budesonide molecules, announced earlier in the year.

“The study outcome is disappointing, however the primary endpoint in this difficult-to-treat patient population presented a high hurdle from the outset,” said principal investigator, professor Tim Harrison, of the Faculty of Medicine and Health Sciences at the University of Nottingham.

“The results suggest that in these study patients with severe asthma, nebulised budesonide is not an appropriate treatment alternative to biologic therapy.”

Harrison said that there was the “distinct possibility” that a specific severe asthma phenotype could gain greater benefit.

“I believe the technology behind VR475 has the potential to be beneficial in the treatment of a wide range of respiratory diseases including asthma.”

Gonzalo de Miquel, Vectura's chief medical officer and executive vice-president of development, added that although the company was disappointed that the results missed statistical significance, he remained confident in its proprietary technology and development capabilities.

“Vectura remains fully committed to enhancing respiratory medications by developing better formulations and superior inhalation systems for patients,” de Miquel said.

“I would like to thank patients, caregivers, investigators and our staff for their participation in what has been a well conducted and executed study.”

Vectura said that as part of the acquisition of Activaero in March 2014, it recognised an intangible asset for the VR475 programme.

Following the results of the study, that asset would be fully impaired in the current financial year, resulting in a negative impact on the group's loss before tax of £40m, and loss after tax of £29m.

With respect to 2019, the board said it expected the net impact to EBITDA of revenue and research and development cost movements to be broadly neutral, as a result of its decision to cease development of VR475.

Research and development guidance for 2019 would be communicated as part of a trading update early in the new year, it confirmed.