All Over For AZ's Fasenra In COPD With Second Trial Fail
Executive Summary
It is curtains for AstraZeneca's asthma therapy Fasenra as a COPD treatment after the failure of the TERRANOVA trial, which could be good news for GSK's fellow interleukin-5 drug Nucala, despite the latter's own mixed Phase III data.
AstraZeneca PLC's slim hopes that its asthma drug Fasenra (benralizumab) could have a future as a treatment for chronic obstructive pulmonary disease have been dashed with the failure of a second Phase III trial in the space of just three weeks.
The company has announced top-line results from the TERRANOVA trial which reveal that Fasenra did not meet the primary endpoint of a statistically significant reduction of exacerbations in patients with moderate to very severe COPD. The study is part of VOYAGER, which AstraZeneca had touted as the largest COPD biologics development program in the world with close to 4,000 patients.
The news follows the failure, reported May 11, of a similar trial, GALATHEA, which also missed the same primary endpoint. Both trials were evaluating the interleukin-5 inhibitor as an add-on to dual or triple inhaled therapy compared with placebo in patients with a history of exacerbations across a range of baseline blood eosinophils.
Although AstraZeneca has not definitively pulled the plug on Fasenra for COPD, and a full evaluation of the data from the two studies is ongoing (with results to be submitted for presentation at a forthcoming medical meeting), the company said it did not currently intend to make a regulatory submission.
Chief medical officer Sean Bohen acknowledged in a statement that the results were "disappointing because uncontrolled COPD patients already on dual or triple inhaled therapy need new treatment options." AstraZeneca noted that about 30-40% of moderate to severe COPD patients on triple inhaled therapy – i.e. long-acting beta-agonists (LABA), long-acting muscarinic antagonists (LAMA) and inhaled corticosteroids (ICS) – remain uncontrolled and continue to experience exacerbations.
Expectations for TERRANOVA were fairly low following the disappointment of GALATHEA. However, Eric Le Berrigaud at Bryan Garnier issued an investor note on May 30 saying that the failures were "surprising" because GlaxoSmithKline PLC’s rival severe asthma drug Nucala (mepolizumab), an IL-5 antagonist, had shown some benefit in COPD.
In its first COPD study – METREO – Nucala did not meet statistical significance in reduction of exacerbation although the results were suggesting a positive trend. The second study, called METREX, was positive and GSK filed Nucala for COPD in the US in November 2017. (Also see "Glaxo Set To File Nucala In COPD, Despite Mixed Phase III Results" - Pink Sheet, 12 Sep, 2017.)
Le Berrigaud noted that with Nucala, GSK has recruited only patients with COPD and high eosinophil counts whereas AstraZeneca had not selected patients and recruited all-comers. He wrote that Fasenra had some specific features including its dosing schedule "which could have offered an edge over Nucala but the different outcomes in COPD between the two drugs is clearly favoring GSK, not only because physicians treating both conditions will prefer the one addressing the two but also because some patients suffer from both asthma and COPD."
Datamonitor Healthcare analyst Chris Mulligan told Scrip that "Fasenra’s exit from COPD now looks almost certain, significantly increasing Nucala’s lead over the competing biologic therapies." He added that "while this obviously improves Nucala’s commercial prospects, the drug's potential in the COPD market is still limited due to its own dubious clinical trial data."
Mulligan argued that the "somewhat inconsistent data" from METREX and METREO make's Nucala’s approval for COPD far from certain. Even if it does get the green light, he said that Nucala would likely be restricted for use in patients with an elevated eosinophil count "and with the limited efficacy shown in the pivotal Phase III trials, reimbursement in cost-sensitive markets may be difficult."
As for Fasenra, despite the COPD disappointment, it is performing well in its approved indication as an add-on treatment for severe eosinophilic asthma. Only approved in the US in November 2017 (and in Europe and Japan in January this year), first-quarter 2018 sales were $21m and AstraZeneca highlighted IQVIA new-to-brand prescription data which shows that third-to-market Fasenra – behind Nucala and Teva Pharmaceutical Industries Ltd.'s Cinqair (respizumab) – tracked in-line or ahead of prior biologics launches in asthma. (Also see "Severe Asthma Market Snapshot: A Competitive Therapy Area That Will Test Payers' Influence" - Scrip, 23 May, 2018.)
Vincent Meunier, an analyst at Morgan Stanley, issued a note saying the TERRANOVA failure is "only a small negative, given low remaining expectations," and forecast $800m sales for Fasenra in 2023 versus consensus estimates of $963m.