Ultomiris fail mars AZ's strong Q2 results
AstraZeneca's Discovery Centre building in Cambridge, UK.
AstraZeneca has served up a robust set of interim results, leavened by strong sales of cancer drugs, but with some mixed pipeline news on the side.
Sales grew 6% to $30.7 billion in the first half, with operating profit shooting up 11% to $10.5 billion, and the company is firmly on track to deliver its target of $80 billion in annual revenues in 2030, said chief executive Pascal Soriot.
That confident outlook comes despite the recent setback for Wainua (eplontersen) in ATTR cardiomyopathy, denting its sales prospects, and the news today that a phase 3 trial of Ultomiris (ravulizumab) in thrombotic microangiopathy after haematopoietic stem cell transplant (HSCT-TMA) – a rare complication of bone marrow transplants – failed to show a positive result in adult and adolescent patients.
While a relatively minor setback for Ultomiris – which grew 14% to nearly $2.6 billion in the first half – the result is a blow for patients and their doctors, as HSCT-TMA is a devastating and life-threatening complication of an HSCT, which is used to treat blood cancers, bone marrow failure disorders, and severe immune conditions.
Ultomiris has previously shown efficacy in paediatric transplant patients, however, so AZ will be able to press ahead with regulatory filings for HSCT-TMA in that group, while discussing with regulators possible ways forward for the drug in older patients.
Good news for ADC pipeline
Meanwhile, on the positive side, AZ also revealed this morning that its CLDN18.2-targeting antibody-drug conjugate (ADC) sonesitatug vedotin (sone-ve) – the lead candidate in its wholly-owned ADC pipeline – hit the mark in a phase 3 trial involving patients with locally advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, or oesophageal adenocarcinoma (EAC) that expresses CLDN18.2.
A big chunk of AZ's sales growth was delivered by its Daiichi Sankyo-partnered ADCs, HER2-targeting Enhertu (trastuzumab deruxtecan) and TROP2-directed Datroway (datopotamab deruxtecan), which are used to treat solid tumours including breast and lung cancers. AZ's revenues from Enhertu grew 32% to $1.7 billion, while Datroway rose more than six-fold to $98 million, en route to what AZ has predicted could be $5 billion at peak.
The company has been investing heavily in its own stable of ADC candidates, based on its proprietary linker and payload technologies, as well as licensing in promising candidates from other companies.
Sone-ve (formerly CMG901), originally developed by KYM Biosciences and licensed by AZ in March 2023, is the first anti-CLDN18.2 ADC to show efficacy in a phase 3 trial, according to AZ.
In the CLARITY-Gastric01 study, which involved patients with tumours in which at least 25% of cells expressed CLDN18.2, there was a significant improvement in overall survival when the ADC was used as second- or third-line therapy, although unusually there was only a trend towards improvement in progression-free survival (PFS), typically an easier objective to hit.
AZ said the results suggest sone-ve could replace classic chemotherapy in this type of cancer. Gastric cancer is the fifth most common cancer worldwide, and the company estimates that around 60% of cases show 25% or greater CLDN18.2 expression.
"We remain confident in the strength of our pipeline and have more than 20 high-value readouts due over the next 18 months," said Soriot.
