AstraZeneca Plc's experimental ovarian cancer drug, olaparib, showed an 83 percent reduction in the risk of disease progression, but a U.S. Food and Drug Administration staff review has questioned whether the result could be reproduced.
The company's shares fell 1.8 percent to 43.89 pounds on the London Stock Exchange.
Olaparib, one of several cancer drugs AstraZeneca has flagged as having strong potential in its defense of a $118 billion take-over bid by Pfizer Inc, is designed as a maintenance therapy for relapsed ovarian cancer in which tumors have responded completely or partially to platinum-based chemotherapy.
"AstraZeneca has put up some pretty lofty expectations," said Damien Conover, an analyst at Morningstar.
The FDA staff report, published on the agency's website on Monday, comes two days ahead of a meeting of outside experts who will discuss whether olaparib's benefits outweigh its risks and whether further data is needed before approval.
The FDA is not obligated to follow the recommendations of its advisory panels but typically does so.
Olaparib, which would be sold under the brand name Lynparza if approved, blocks the activity of Poly (ADP-ribose) polymerase (PARP), an enzyme that plays a key role in cell repair.
Patients in a clinical trial had a seven-month median improvement in progression-free survival, a benchmark that measures the amount of time a patient lives without the disease getting worse.
The drug is aimed at women with certain hereditary BRCA gene mutations that account for an estimated 10-15 percent of all cases of ovarian cancer, or about 2,000 cases a year in the United States.
Patients with the mutations tend to respond better to chemotherapy so they are likely to undergo multiple rounds. Periods away from chemotherapy allow the patient to recover from side effects before undergoing a new round.
In theory, olaparib would extend that period of recovery time.
The way the company conducted its data analysis, however, has created some uncertainty about the validity of the results, the FDA review said. AstraZeneca collected some of the data retrospectively using archived blood samples, calling into question "the reliability of the estimation of treatment effect," the review said.
Data suggests most patients will experience some degree of progression-free survival but the benefit may be due in part to a control arm that performed unusually poorly, the review said, adding there was no difference on overall survival between the two treatment arms.
AstraZeneca has said sales of olaparib could reach $2 billion a year, although some Wall Street estimates peg the potential sales at half that figure.
Ovarian cancer is the fifth leading cause of cancer death in women, with an estimated 22,000 new cases diagnosed and 14,270 deaths in the United States in 2014.
Olaparib's most common side effects were nausea, fatigue, abdominal pain, vomiting, diarrhea and anemia.
(Reporting by Toni Clarke in Washington; Editing by Bill Trott and Paul Simao)