AstraZeneca’s TLR9 oligonucleotide misses goal in asthma phase 2

AstraZeneca's Cambridge, U.K. campus. (AstraZeneca)

A phase 2a trial of AstraZeneca’s AZD1419 has missed its primary endpoint. AstraZeneca moved the Dynavax-partnered TLR9 agonist into the trial in the belief it could improve time to loss of asthma control in patients with eosinophilic, moderate-to-severe forms of the disease.

Dynavax designed AZD1419, an inhaled synthetic oligonucleotide containing immunostimulatory CpG motifs, to be a potent and specific agonist for TLR9. The idea was to trigger prolonged reductions in asthma symptoms by altering how the immune system responds to allergens. If AZD1419 achieved that goal, it may have freed patients from the need to take inhaled corticosteroids, muscarinic antagonists and beta agonists as maintenance therapies.

However, if the phase 2a is any guide, AZD1419 will fall short of that goal. AstraZeneca is yet to make a statement about the trial, but Dynavax revealed it missed the primary endpoint of time to loss of asthma control.


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According to Dynavax, the 13-week trial suggested the drug is safe, well tolerated and activates the TLR9 pathway. The positives are more than offset by the primary endpoint miss, though. AstraZeneca is now going through the data before making a decision on the future of the program. 

AstraZeneca began working with Dynavax in 2006 and amended the agreement five years later to get AZD1419 into the clinic. Back then, AstraZeneca paid $3 million to get the clinical program started and committed to handing over $20 million to cover the cost of Dynavax taking the drug through to phase 2a.

In 2014, the partners decided to skip phase 1b and jump straight into phase 2b on the strength of data from 45 healthy volunteers. Progress slowed after that, though. Dynavax had expected to move into phase 2a in the first half of 2015. In January 2016, with the trial yet to start, AstraZeneca took responsibility for running the phase 2a.

AstraZeneca’s action got the program moving forward again. Enrollment in the trial began around the start of 2017, and the study wrapped up on schedule two months ago.  

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