AZ stakes its claim in immunotherapy with bladder cancer filing

After looking like it could get left far behind by rivals in immunotherapy, AstraZeneca has made its first filing for PD-L1 drug durvalumab .

The UK-headquartered firm announced that the FDA had accepted the filing of its PD-L1 drug on Friday in second line treatment of metastatic urothelial carcinoma (UC), which would put it into direct competition with Roche’s Tecentriq, already approved in this indication.

AstraZeneca had once hoped to file durvalumab as a monotherapy in non-small cell lung cancer (NSCLC) but had to change plans after PD-1 checkpoint inhibitors Merck’s Keytruda and BMS’ Opdivo rapidly gained approval and market uptake.

Now a year on from that decision, AstraZeneca has its first filing for durvalumab, which it is counting on to be a multi-billion dollar blockbuster.

However Roche’s Tecentriq, (also a PD-L1 blocker) gained approval for UC in May this year, putting pressure on AstraZeneca’s drug to outperform its rival or face thin pickings once on the market.

AstraZeneca have been emphasising the importance of combinations in immunotherapy, and maintain they have the lead in clinical trials studying a PD-1/PD-L1 in combination with other agents.

Among its many trials of durvalumab, it is being studied in combination with tremelimumab (a CTLA-4 mAb) in the phase 3 DANUBE trial as 1st-line treatment for patients with metastatic UC, regardless of eligibility for cisplatin-based chemotherapy.

The combination of durvalumab and tremelimumab is also being studied in phase 3 trials in NSCLC, head and neck squamous cell carcinoma (HNSCC) and in phase 2 and earlier trials in gastric cancer, pancreatic cancer, hepatocellular carcinoma (HCC) and blood cancers.

Nevertheless, AstraZeneca is likely to be fifth to market with its checkpoint inhibitor – Pfizer and Merck KgAa have already filed their Avelumab for patients with metastatic Merkel cell carcinoma (MCC).

AstraZeneca’s immunotherapy pipeline has also just received a vote of confidence from analysts Leerink, naming AZ as its favoured big pharma stock for 2017, saying its prospects are currently underestimated.

The trial to watch is MYSTIC, which looks at durvalumab + tremelimumab as a first-line treatment for NSCLC. Patients are being enrolled regardless of PD-L1 expression in the phase 3 trial, but AZ could decide to only focus on high expressers of PD-L1 when performing its primary analysis.

It still looks like a long shot, but if MYSTIC can produce signs of outperforming Keytruda monotherapy (and standard chemotherapy) as a first line NSCLC treatment, the two-drug combination could become a major player.

Revenues of up to $4 billion by 2021 are forecast by Leerink, which would be a major contributor to AZ’s ambitious revenue growth target.

Leerink analysts predict that the results are unlikely to show outright failure, though the final judgement could depend on the levels of toxicity seen in patients, (well understood in CTLA-4 drugs) as well as outright efficacy.

Topline results from the trial are expected in the first half of 2017, which will prove pivotal for AstraZeneca.