NEW YORK – AstraZeneca is betting that Gracell Biotechnology's clinical stage CAR T-cell therapy platform, which it expects to gain in its pending acquisition of the company, will offer significant advantages over competing CAR T-cell therapies for treating multiple myeloma and other hematologic malignancies.
AstraZeneca executives discussed their plans for integrating Gracell's products during a call Thursday to discuss fourth quarter and full-year 2023 financial results. In Q4, the firm's total revenue rose 7 percent to $12.02 billion compared to Q4 2022, but fell short of the $12.09 billion analysts were expecting on average. Oncology products contributed $4.99 billion to Q4 revenue, increasing 23 percent over the year-ago period.
In December 2023, AstraZeneca announced it would acquire Gracell in a deal with an upfront and contingent value of approximately $1.2 billion. The acquisition is slated to close in Q1 2024. Suzhou, China-based Gracell developed GC012F, its lead asset, using the FastCAR platform, a manufacturing process designed to overcome common challenges facing autologous CAR T-cell production, including slow turnaround, poor quality, and high cost.
FastCAR offers several key benefits over competing technologies, according to Susan Galbraith, AstraZeneca's head of oncology R&D, including reduced manufacturing time, increased manufacturing capacity, and improved predictability for CAR T-cell delivery. CAR-T production typically takes from one week to three weeks, whereas it can take between 22 hours and 36 hours to manufacture the cells using FastCAR, Galbraith said.
"A lower dose of cells needs to be manufactured for each patient, which reduces the risk of cytokine release syndrome," she noted, adding that "the shorter manufacturing time delivers fitter T cells, and this potentially improves the efficacy of this [CAR T-cell therapy]."
Gracell's GC012F is a BCMA- and CD19-directed autologous CAR T-cell therapy that the company is studying in several clinical trials, including an ongoing Phase Ib/II trial of patients with relapsed and refractory multiple myeloma. It also expects to begin a Phase I/II trial of GC012F in refractory systemic lupus erythematosus this year. And last month, the US Food and Drug Administration cleared Gracell to begin a Phase I trial of GC012F as an early-line therapy for multiple myeloma.
There are also several investigator-initiated trials of GC012F underway in multiple myeloma, lupus, and B-cell non-Hodgkin lymphoma.
Gracell presented data from one such investigator-initiated trial at the American Society of Hematology Annual Meeting in December. In that trial, which was studying GC012F in newly diagnosed multiple myeloma patients, the cell therapy showed a 100 percent overall response rate and a 95 percent to 100 percent minimal residual disease negativity rate at 6 months to 12 months after treatment. Median progression-free survival and median duration of response had not been reached at a median follow-up time of 18.8 months.
The safety analysis found that 27 percent of patients experienced low-grade cytokine release syndrome, which resolved within four days, and there were no cases of immune effector cell-associated toxicity or neurotoxicity of any grade. "This demonstrates the promise of this potential therapy when you move it into an earlier-line setting," Galbraith said, adding that AstraZeneca sees potential for GC012F in hematologic malignancies beyond multiple myeloma.
The FDA in November issued a warning that patients receiving autologous CAR T-cell therapies targeting BCMA and CD19 may be at risk of developing new T-cell malignancies, and in January, the agency notified manufacturers of such immunotherapies that they must revise product package inserts to include a boxed warning about those risks. AstraZeneca management did not address these concerns during the earnings call and did not respond to a request for comment on it by publication time.
Q4 2023 performance
Outside of the Gracell acquisition, several precision oncology assets in AstraZeneca's pipeline performed well during Q4. Its top-selling oncology product, the tyrosine kinase inhibitor Tagrisso (osimertinib), recorded sales of $1.42 billion in Q4 2023, an increase of 6 percent compared to Q4 2022. The firm markets Tagrisso as an adjuvant and first-line therapy for EGFR-mutated non-small cell lung cancer. Over the same period, sales for the PARP inhibitor Lynparza (olaparib) increased 8 percent to $741 million, and sales of the immunotherapy Imfinzi (durvalumab) increased 51 percent to $1.14 billion.
Also during Q4 2023, the HER2-targeted antibody-drug conjugate Enhertu (trastuzumab deruxtecan), which AstraZeneca markets with Daiichi Sankyo, recorded $83 million in sales, more than double what the drug contributed during the same period in 2022.
The company reported $6 million in Q4 sales for its recently launched AKT1/2/3 inhibitor Truqap (capivasertib), which was approved in the US in November as a treatment for hormone receptor-positive, HER2-negative advanced or metastatic breast cancer bearing alterations in PIK3CA, AKTT1, or PTEN.
"With the exciting approval of Truqap, we have the opportunity to further extend our leadership in breast cancer, including in the hormone receptor-positive landscape," David Fredrickson, AstraZeneca's executive VP of oncology, said, referencing a strategy AstraZeneca announced in July 2023 to entirely replace chemotherapy in the late-line breast cancer setting across all subtypes with its targeted therapies.
AstraZeneca posted a profit of $959 million, or $.62 per share, in Q4 2023, compared to a profit of $902 million, or $.58 per share, in Q4 2022. The consensus Wall Street EPS estimate was $.79.
In 2023, AstraZeneca's revenues were $45.81 billion, a 3 percent increase compared to 2022, and slightly under the $45.87 billion that analysts were expecting on average.
The oncology segment contributed $17.15 billion, a 17 percent increase compared to 2022. Over the same period, sales of Tagrisso and Lynparza increased 7 percent to $5.80 billion and $2.81 billion, respectively; sales of Imfinzi jumped 52 percent to $4.24 billion; and Enhertu brought in $261 million, more than triple the revenue in 2022.
The firm recorded a profit of $5.96 billion in 2023, or $3.84 per share, compared to $3.29 billion, or $2.12 per share, in 2022. Analysts, on average, had projected EPS of $3.70.
The firm finished the year with $5.64 billion in cash and cash equivalents.