The headline of this article has been updated to show the correct name of AstraZeneca's investigational compound camizestrant.
NEW YORK – AstraZeneca is hoping for a positive readout this year from the SERENA-6 Phase III trial of its investigational complete estrogen receptor antagonist camizestrant, which could set the drug up to be combined with other molecules in the company's growing breast cancer franchise.
AstraZeneca executives outlined expectations for camizestrant in a call Thursday morning with investors to discuss its full year 2024 and fourth quarter financial results. The company's targeted breast cancer therapies performed well in Q4 2024. The HER2-targeted antibody-drug conjugate Enhertu (trastuzumab deruxtecan), which AstraZeneca markets with Daiichi Sankyo, recorded $540 million in sales, a 48 percent increase over the same period in 2023. The company reported $163 million in Q4 sales for the AKT1/2/3 inhibitor Truqap (capivasertib), more than 10 times its sales in the year-ago period. Truqap was approved in the US in November 2023 as a treatment for hormone receptor-positive, HER2-negative advanced or metastatic breast cancer bearing alterations in PIK3CA, AKT1, or PTEN.
"I'm pleased to report that Truqap is now the market leader in the second-line biomarker-altered patient population," Dave Fredrickson, AstraZeneca's executive VP of oncology, said during the call.
In Q4, the firm's total revenue rose 24 percent to $14.89 billion, compared to $12.02 billion in Q4 2023, exceeding the $13.34 billion analysts were expecting on average. Oncology products contributed $6.34 billion to Q4 2024 revenue, increasing 27 percent versus the year-ago period.
AstraZeneca announced in July 2023 a strategy to entirely replace chemotherapy in the late-line breast cancer setting across all subtypes with its targeted therapies. The company is now looking forward to adding camizestrant to its breast cancer armamentarium, with an anticipated positive readout from SERENA-6 in the second half of 2025. In the trial, AstraZeneca researchers are comparing camizestrant plus a CDK4/6 inhibitor to an aromatase inhibitor plus a CDK4/6 inhibitor in patients with hormone receptor-positive, HER2-negative metastatic breast cancer with an ESR1 mutation.
The trial would give the company its first Phase III data on camizestrant, which targets the estrogen receptor (ER) with a dual mechanism. Camizestrant inhibits ER transcriptional activity and degrades the receptor, while in comparison, aromatase inhibitors like anastrozole and letrozole merely reduce the production of estrogen, which decreases ligand-driven transcriptional activity but leaves ER in place.
"This dual action of camizestrant gives us confidence that it can provide greater benefit to patients than aromatase inhibitors, regardless of ESR1 mutation status," Susan Galbraith, AstraZeneca executive VP of oncology R&D, said on the call. The company's confidence is supported by data from the Phase II SERENA-2 trial, in which the drugmaker saw a progression-free survival benefit for camizestrant over fulvestrant in a head-to-head comparison. In the trial, patients on a 250 mg dose of camizestrant lived a median 7.7 months without disease progression or death compared to 3.7 months for those on fulvestrant.
"These data taken together with the low discontinuation rates, low rates of [gastrointestinal] toxicities, which can be bothersome to patients, and the ability to combine chemistry with all three major CDK4/6 inhibitors … drive our confidence," Galbraith said. "SERENA-6 is the first Phase III trial to read out and investigate switching the endocrine partner of any CDK4/6 inhibitor from an aromatase inhibitor to camizestrant on emergence of an ESR1 mutation during first-line treatment."
In 2023, the US Food and Drug Administration approved Menarini Group's SERD Orserdu (elacestrant) for patients with ER-positive, HER2-negative, ESR1-mutated advanced breast cancer after progression on endocrine therapy. The company, however, is exploring the potential of Orserdu in combination with Eli Lilly's CDK 4/6 inhibitor Verzenio (abemaciclib) in second-line ER-positive advanced breast cancer and has evidence suggesting that the combination appears to have activity in patients regardless of their ESR1 mutations status.
At the San Antonio Breast Cancer Symposium in 2024, Eli Lilly's SERD imlunestrant, on its own, also appeared to stave off cancer progression longer than standard endocrine therapy in patients with ER-positive advanced breast cancer who developed resistance to frontline hormone therapy due to ESR1 mutations. However, in the same Phase III EMBER-3 trial, when the SERD was given as a second-line treatment with Verzenio, the combination benefited patients not only if they had ESR1-driven endocrine resistance but also if they'd developed resistance through other mechanisms.
If approved, camizestrant could face competition from these SERDs and Olema Oncology's complete estrogen receptor antagonist palazestrant, which the company is evaluating in one Phase III clinical trial and is planning to study in a second beginning this year. Like camizestrant, palazestrant is designed to block the estrogen receptor and also to degrade it. In a Phase II trial of palazestrant in patients with estrogen receptor-positive, HER2-negative advanced or metastatic breast cancer who relapsed or progressed on one or two lines of prior therapy, ESR1-mutant patients on palazestrant had a 7.3-month median progression-free survival. If all goes well, Olema is looking ahead to a possible 2027 launch for palazestrant.
Q4 2024 performance
Outside of its breast cancer program, several precision oncology assets in AstraZeneca's pipeline performed well during Q4. The firm's top-selling oncology product, the EGFR inhibitor Tagrisso (osimertinib) recorded sales of $1.70 billion in Q4 2024, an increase of 20 percent compared to Q4 2023. The company markets Tagrisso as an adjuvant and first-line therapy for EGFR-mutated non-small cell lung cancer.
Fredrickson said Tagrisso's uptake was strong across all indications. "In the front-line setting, Tagrisso achieved over 75 percent market share globally, with close to 85 percent market share in the US," he said, noting that the drug made steady gains in the adjuvant setting and had encouraging early launch uptake in early-stage unresectable lung cancer.
Over the same period, sales for the PARP inhibitor Lynparza (olaparib) increased 46 percent to $1.44 billion, and sales of the immunotherapy Imfinzi (durvalumab) increased 16 percent to $1.25 billion. Lynparza's sales triggered a $600 million milestone payment in the fourth quarter from a 2017 codevelopment and co-commercialization agreement with Merck, Fredrickson said.
AstraZeneca posted a profit of $1.5 billion, or $.97 per share, in Q4 2024, compared to a profit of $959 million, or $.62 per share, in Q4 2023. The consensus Wall Street EPS estimate was $.81.
Full-year 2024
In 2024, AstraZeneca's total revenue was $54.07 billion, an 18 percent increase compared to $45.81 billion in 2023 and beating the $53.38 billion that analysts were expecting on average.
The oncology segment contributed $22.35 billion, a 21 percent increase compared to 2023. Over the same period, sales of Tagrisso increased 13 percent to $6.58 billion and Lynparza sales increased 20 percent to $3.67 billion. Sales of Imfinzi jumped 17 percent to $4.72 billion, and Enhertu brought in $1.98 billion, 54 percent more than in 2023.
The firm recorded a profit of $7.04 billion in 2024, or $4.54 per share, compared to $5.96 billion, or $3.84 per share, in 2023. Analysts, on average, had projected EPS of $4.10.
AstraZeneca finished the year with $5.49 billion in cash and cash equivalents.
In 2025, the company expects total revenue to increase by a high-single-digit percentage.