Cancer drugs buttress AstraZeneca as questions swirl around new indications

While a GLP-1 weight loss licensing deal grabbed headlines in AstraZeneca's third-quarter earnings report, oncology remains the British pharma's largest business and primary growth driver.

Cancer drugs together brought in $4.7 billion in sales for AstraZeneca in the third quarter, up 17% at constant exchange rates over the same period last year. The portfolio constituted about 40% of the company’s total revenue of $11.5 billion during the quarter.

But several key oncology products fell short of Wall Street analysts’ expectations, including EGFR lung cancer med Tagrisso, Merck & Co.-partnered PARP inhibitor Lynparza, BTK inhibitor Calquence and Daiichi Sankyo-partnered antibody-drug conjugate Enhertu.

With $1.47 billion in third-quarter sales, Tagrisso not only missed consensus by 2% but actually declined sequentially. While Tagrisso saw relatively steady quarterly sales in the U.S., a recent price reduction in Japan and reduced promotional activities in China because of a government-led crackdown on hospital corruption put a damper on the drug.

After years as the leading EGFR inhibitor, Tagrisso lately faces some uncertainty about its future. A combination of Tagrisso and chemotherapy recently showed impressive benefits in staving off tumor progression compared with Tagrisso alone in newly diagnosed, metastatic EGFR-mutant non-small cell lung cancer in the phase 3 FLAURA2 trial. But experts want to see an overall survival advantage, while data there remained immature.

When doctors and patients select their treatments, the benefit-risk consideration includes more than just efficacy, but also the side effect profile, as well as convenience of administration, AZ’s oncology business chief Dave Fredrickson said during the company’s third-quarter earnings call Thursday.

Fredrickson argued that the chemo combo could be an option for patients who need intensification of treatment, including those with brain metastases or with the L858R mutation. Plus, doctors are already familiar with the side effects from chemotherapy, and they can discontinue the cytotoxic agent and continue with Tagrisso alone, he said.

But AZ also believes that Tagrisso monotherapy will continue to be an important option for the majority of patients as an oral regimen with a proven overall survival benefit and proven tolerability profile, Fredrickson added.

Tagrisso needs an intensified regimen to fend off a potential competitor in Johnson & Johnson’s Rybrevant-lazertinib combo, which also beat Tagrisso alone on progression-free survival in first-line NSCLC. Overall survival data from the phase 3 MARIPOSA trial showed a trend favoring the J&J regimen, and J&J suggested that the trial could eventually meet statistical significance on that key endpoint.

In what Fredrickson called “probably the most significant Tagrisso growth driver” in the near term, AZ is also testing Tagrisso as a maintenance therapy following chemoradiation in EGFR-mutant, stage 3 NSCLC. That phase 3 LAURA trial is expected to read out in the first half of 2024, and if positive, could open up a “sizable opportunity” for Tagrisso, he said.

Elsewhere in AZ’s oncology portfolio, Lynparza has been under pressure thanks to reduced adoption of the entire PARP class and label restrictions in ovarian cancer. The drug reeled in $702 million in sales in the third quarter, down 2% over the prior three months.

AZ recently reported positive data for adding Lynparza to PD-L1 inhibitor Imfinzi in first-line advanced endometrial cancer. AZ is discussing with regulatory agencies around a potential application, oncology R&D head Susan Galbraith, Ph.D., said on the call.

The exact indication AZ will pursue remains unclear. As Galbraith noted, the addition of Lynparza showed a deeper benefit in patients with DNA mismatch repair-proficient or PD-L1-positive tumors.

Meanwhile, blood cancer med Calquence missed consensus by 7% with third-quarter sales of $654 million. Competition from BeiGene’s Brukinsa definitely didn’t help. But Calquence remained the leading BTK inhibitor by new-to-brand share, according to Fredrickson.

It’s a bit surprising how AZ’s rising star Enhertu underperformed expectations. Enhertu’s third-quarter global sales reached $675 million, which represents a mere 2% quarter-over-quarter growth.

One positive piece of news for Enhertu, as Fredrickson noted, is that second-line patients with HER2-positive breast cancer and those with HER2-low disease appeared to be staying on treatment longer than expected. Growing new patient share and further extending treatment duration could help Enhertu growth in those indications, he said.

AZ is moving along its other ADC projects. The company plans to file TROP2-targeted Dato-DXd with regulators in both NSCLC and breast cancer.