The pharmaceutical company AstraZeneca retracted a paper and acknowledged that some preclinical data were falsified regarding its developmental agent acalabrutinib. The drug is under investigation for use in a number of malignancies, including chronic lymphocytic leukemia (CLL), multiple myeloma, ovarian cancer, and follicular lymphoma.
The retracted paper was published in Cancer Research in 2015, and focused on a mouse model of pancreatic cancer. The company has said that the data in the paper were falsified, according to a report by Retraction Watch. Though the study was “contributory” to the decision to move forward with development of the agent, it was not the sole piece of evidence, company officials told Retraction Watch, adding that the falsified data came from a single, former employee.
Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor. It was granted Breakthrough Therapy designation and subsequently Priority Review status by the US Food and Drug Administration earlier this year, specifically for its use in treating relapsed/refractory mantle cell lymphoma in patients who have received at least one prior therapy.
The agent has also shown promise in CLL. A paper published in 2016 in the New England Journal of Medicine showed that in a phase I/II trial there were good response rates and a reasonable safety profile in 61 patients with relapsed CLL.
After a median follow-up of 14.3 months, the overall response rate was 95%; a total of 85% had a partial response and 10% had a partial response with lymphocytosis, and the remaining 5% had stable disease. All patients with a chromosome 17p13.1 deletion achieved a response. Most adverse events were low-grade, and the most common adverse events included headache, diarrhea, and increased weight.
AstraZeneca has claimed that the preclinical data issue has no impact on the ongoing human clinical trials, and that there is no risk to patients in those trials. Acalabrutinib has been tested in more than 2,000 patients in more than 25 trials.