Vectura Group said today it has halted development of its asthma drug-device combination VR475 following its failure in a Phase III European trial.

VR475 consists of a budesonide inhalation suspension delivered by the proprietary VR475 Inhalation System, a breath-actuated jet nebulizer. Vectura acknowledged that the combination product missed its primary endpoint in the trial, designed to assess VR475 in adult and adolescent patients with severe uncontrolled asthma.

While topline results indicated a reduction in the annualized rate of clinically significant exacerbations compared to placebo among patients receiving either VR475 1 mg or VR475 0.5 mg doses twice daily over a 52-week treatment period, the results did not reach statistical significance, Vectura said.

The open-label arm with conventional nebulizer also failed to reach statistical significance vs placebo.

“Although we are disappointed that these results missed statistical significance, I remain confident in our proprietary technology and development capabilities,” Gonzalo de Miquel, Vectura’s CMO & EVP, development, said in a statement. “Vectura remains fully committed to enhancing respiratory medications by developing better formulations and superior inhalation systems for patients.

Vectura added VR475 to its pipeline in 2014 when it acquired Activaero group for €130 million ($147.6 million).

Vectura said it will complete a full analysis of the primary and secondary data for the failed VR475 trial, with the intent of presenting complete study results at an unspecified upcoming medical conference. The company also said it will seek to publish the data in a peer-reviewed journal.

Available safety data for VR475 are consistent with the known profile of inhaled budesonide, Vectura added.

Vectura disclosed that an initial review of the available secondary endpoints and the safety data showed unspecified endpoints achieving statistically significant and clinically meaningful differences between VR475 and placebo, and versus conventionally nebulized budesonide. These results, according to the company, reinforced how its guided inhalation system differed from conventional nebulization.

Pipeline Confidence

That reinforcement, the company said, gives it confidence in its ongoing clinical program to develop its Phase II candidate VR647, a wholly-owned drug-device combination being developed for pediatric asthma in the U.S.; and three additional early-stage nebulization programs that use non-budesonide molecules, and that were announced earlier this year.

In August, Vectura said a pair of positive studies—one assessing pharmacokinetics and the other, usability with a mouthpiece—supported advancement of VR647 into a Phase III development program. The studies showed that VR647 had the potential to achieve same lung deposition with lower delivered dose than existing marketed treatments without compromising exposure or safety—with potential inhalation time being approximately half of that delivered with existing conventional nebulizers.

“Whether there is a specific severe asthma phenotype who could gain greater benefit remains a distinct possibility,” stated Tim Harrison, MBBS, BSc, FRCP, MD, MSc, professor at the University of Nottingham and the Phase III trial’s principal investigator. “I believe the technology behind VR475 has the potential to be beneficial in the treatment of a wide range of respiratory diseases including asthma.”

“The study outcome is disappointing,” Dr. Harrison said of the failed trial. “However, the primary endpoint in this difficult-to-treat patient population presented a high hurdle from the outset.  The results suggest that in these study patients with severe asthma, nebulized budesonide is not an appropriate treatment alternative to biologic therapy.”

The scrapping of VR475, Vectura said, will result in a loss before tax of £40 million ($51.4 million), and an after-tax loss of £29 million ($37.2 million). The company said it expected the 2019 net impact of revenue and R&D costs on earnings before interest, taxes, depreciation, and amortization (EBITDA) to be “broadly neutral,” though the company’s R&D guidance will come early in the New Year.

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