Dive Brief:
- Verona Pharma plc highlighted positive topline data on Monday supporting the efficacy of its experimental dual PDE3/PDE4 inhibitor, announcing a Phase 2b study showed clinically and statistically significant improvements in lung function in patients with chronic obstructive pulmonary disease (COPD).
- RPL554 demonstrated significance at all dose levels (.75 mg, 1.5 mg, 3 mg, and 6 mg), as measured by improvements in peak forced expiratory volume in one second (FEV1). The study also reduced breathlessness over time — a secondary endpoint — and met its other secondary endpoints of improved 12–hour average FEV1, COPD symptoms and quality of life scores.
- Verona's candidate, one of the first novel bronchodilators to be pitched in many years, features a dual mechanism of action: synergistic inhibition of phosphodiesterase 3 (PDE3) and PDE4. The complementary effect of RPL554's bronchodilatory and anti-inflammatory properties could have enormous potential for patients with severe disease.
Dive Insight:
Jefferies analysts called the drug a potential blockbuster in a March 26 note to investors, and mentioned that if Phase 2 trials go smoothly, the one-product company would possess a "compelling out-licensing opportunity in 2-3 years' time" or may be interested in selling the company along with its asset.
The success will be especially important to Verona, as the drug is the firm's only pipeline asset. Jefferies' analysts noted that the phosphodiesterase-based medications (such as PDE3, PDE4 and PDE5 inhibitors) have demonstrated significant cough suppression, and could be superior treatments to current antitussive drugs, which are associated with adverse effects and sometimes do not sufficiently quell cough.
The global asthma and COPD market is expected to reach nearly $57 million by 2025, according to a January 2018 report from Research and Markets.
The current standard of care for COPD is a combination of an inhaled bronchodilator and anti-inflammatory glucocorticosteroid — the same treatment plan that is typically recommended for those who suffer from asthma. This usually involves two medications with two different purposes.
Rather than take separate drugs to promote bronchodilation and prevent inflammation, the researchers' goal was to find a novel drug that had both properties in a single molecule with complementary activity. And, unlike previous phosphodiesterase inhibitors licensed for the treatment of COPD — such as AstraZeneca plc’s Daliresp (roflumilast), an oral PDE4 inhibitor approved in 2011 — RPL554 harnesses both bronchodilation and anti-inflammation, and can be nebulized rather than administered as a pill.
AstraZeneca's Fasenra (benralizumab) and GlaxoSmithKline plc's Nucala (mepolizumab) are both antibody-based treatments that are being investigated in late-stage trials for their efficacy in COPD. Other investigational candidates that are garnering interest include AstraZeneca's PT010 and Theravance Biopharma Inc.'s revefenacin. AstraZeneca's Bevespi Aerosphere (glycopyrrolate and formoterol fumarate) inhalation aerosol was approved in 2016 as a maintenance treatment of airflow obstruction in patients with COPD.
In addition to COPD, RPL554 is also being studied as a potential treatment for asthma in the U.S. In the UK, the drug already has topline data from a Phase 2b study on cystic fibrosis, which show that the medication successfully reduced sputum levels.