AstraZeneca reports twin trial news, but Celgene Imfinzi delay

AstraZeneca has put out a pair of positive respiratory updates, one from Phase III trials of combined treatment Duaklir that is being developed with Circassia Pharmaceuticals, and the other being Phase IIb trials of tezepelumab.

Later on Thursday it was revealed that the US Food & Drug Administration has halted several immuno‑oncology studies, including placing a partial hold on five trials and a full hold on another conducted by Astrazeneca and Celgene in the US, due to risks identified in similar trials elsewhere.

The 'Fusion' trials have been testing the FTSE 100 company's Imfinzi, an anti-PD-L1 antibody known generically durvalumab, in combination with immunomodulatory agents in various blood cancers.

The FDA decision was said to be based on risks identified in other trials for an anti-PD-1 agent called pembrolizumab in patients with multiple myeloma in combination with immunomodulatory agents, though Astra stressed that no imbalance has been observed in the Fusion programme and that other trials with Imfinzi in haematological malignancies and other tumour types were continuing unchanged.

The clinical holds would allow for additional information to be collected to further understand the risk benefit profile of the programme.

RESPIRATORY BOOST

On the upside, respiratory treatment Duaklir met its primary targets of demonstrating that its dual-drug formulation produced a statistically-significant improvement in lung function in patients with moderate to very severe stable chronic obstructive pulmonary disease compared to the single elements, while biologic tezepelumab produced a significant reduction in the annual asthma exacerbation rate compared with placebo in patients with severe, uncontrolled asthma.

Duaklir, which is being tested as a twice-daily combination of long-acting muscarinic antagonist (LAMA) aclidinium bromide and long-acting beta-agonist (LABA) formoterol fumarate, showed no unusual efficacy, safety and tolerability problems and is likely to submitted to the US Food and Drug Administration in the first half of 2018.

Under a deal struck in April, Oxford-based Circassia Pharmaceuticals will own the rights to Duaklir in the US, being responsible for conducting the product's development and marketing in the country.

In addition to Amplify's positive clinical results, AstraZeneca and Circassia believe the study trial materials' in vitro comparability data also meet FDA requirements.

Circassia chief executive Steve Harris said: "With treatment guidelines now placing a greater emphasis on LAMA/LABA combinations, we look forward to our partner AstraZeneca filing an NDA for Duaklir in the coming months."

Tezepelumab, on the other hand, is a first-in-class anti-TSLP (thymic stromal lymphopoietin) monoclonal antibody that is being developed in collaboration with Amgen.

TSLP is an substance the lung produces in response to inflammatory stimuli such as allergens, viruses and other pathogens.

"In asthma patients, TSLP functions as an upstream epithelial 'master-switch' right at the start of the inflammation cascade," explained Bahija Jallal, executive vice president in charge of Astra's MedImmune biologics arm.

"By binding to TSLP, tezepelumab impacts multiple downstream inflammatory pathways associated with asthma, as shown by striking reductions in the level of multiple biomarkers in the PATHWAY trial, including blood eosinophils, IgE and FeNO. This broad biomarker response is unprecedented among respiratory biologics and reflects our commitment to leading respiratory science for unmet medical needs."

The Phase IIb study showed annual asthma exacerbation rate reductions of 61%, 71% and 66% in the tezepelumab arms receiving either 70mg or 210mg every four weeks or 280mg every two weeks.

Tezepelumab is being tested as an add-on therapy to patients with a history of asthma exacerbations and uncontrolled asthma despite receiving inhaled corticosteroids/long-acting beta-agonists with or without oral corticosteroids and additional asthma controllers.

Dr Jonathan Corren, principal investigator of the Pathway trial at the David Geffen School of Medicine, UCLA, said: "These efficacy results strongly confirm that TSLP is an important mediator of inflammation in severe asthma. Due to its activity early in the inflammatory cascade, tezepelumab may be suitable for patients with both T2 and non-T2 driven asthma, including those ineligible for current biologic therapies which only target the T2 pathway."