Updated from 1:26 p.m. EDT
experimental drug darusentan was able to significantly lower blood pressure in patients suffering from resistant hypertension, but a higher rate of heart-related side effects tied to the drug also raised some concerns.
Investors were focusing more on darusentan's side effects than its efficacy Friday, sending Gilead shares down 3.1% to $44.01.
Results from a phase III study of darusentan are being presented Friday afternoon at a meeting of the American Society of Hypertension in San Francisco. Gilead pre-announced some of the details of the darusentan presentation in a press release Friday morning. The company disclosed
from this study in April.
Darusentan, a once-a-day pill, is being developed as a treatment for resistant hypertension, defined as high blood pressure that is not alleviated by treatment with a stable of other drugs.
As had been previously reported, all three doses of darusentan tested were able to reduce systolic and diastolic blood pressure compared to placebo after 14 weeks of treatment. The results were statistically significant, achieving the co-primary endpoints of the study.
Moreover, more than half the darusentan-treated patients achieved their stated blood-pressure reduction goal compared to one quarter of patients treated with a placebo, Gilead said.
But five patients treated with darusentan reported cardiovascular events: Two patients suffered non-fatal heart attacks, while three other patients experienced episodes of heart failure that responded to treatment.
By comparison, one patient in the placebo arm of the study suffered a fatal heart attack.
The study evaluated 379 patients.
The ultimate goal of treating resistant hypertension is to reduce a patient's risk of suffering a heart attack or some other form cardiovascular disease. The positive effect that darusentan has on reducing blood pressure may be moot if the drug also increases the cardiovascular risk for patients.
This was the concern weighing on Gilead's stock price Friday, and it's analogous in some respects to the concerns that emerged last year over
diabetes drug Avandia.
Dr. Michael Weber, professor of medicine at the SUNY Downstate Medical College of Medicine in Brooklyn, N.Y., and the lead investigator on the darusentan study, says the darusentan safety concerns are overblown.
"My guess is that darusentan will ultimately result in a 20 to 40% reduction in the risk of cardiovascular events for these very difficult-to-treat patients. Darusentan is a very beneficial intervention that is reducing, not adding to, the risk of cardiovascular events," he said in an interview with
Weber said the two patients who suffered non-fatal heart attacks while being treated with darusentan had existing heart disease, so the outcome is not surprising, especially since one patient in the placebo arm of the studied died from a heart attack.
Of the three other darusentan patients who suffered episodes of heart failure, one patient had heart failure entering the study and should therefore not have been allowed to enroll. The heart failure in the other two patients was caused by the build-up of fluid in their bodies, known as edema, which can cause the heart to work harder. The blood-pumping ability of both patients' hearts remained strong throughout, and the edema and heart failure were treated successful with commonly used diuretics, according to Weber.
"Darusentan belongs to a class of drugs that is known to cause fluid retention, so we will need to instruct doctors on how to treat these patients when it occurs. But that can be done easily," he said. Weber serves as a consultant to Gilead and other companies developing drugs to treat hypertension.
Among the three dosage groups, edema was reported in 20%, 24% and 15% of darusentan-treated patients compared to 10% for placebo patients, according to the study results.
Sell-side analysts had mixed reactions to the disclosures of darusentan's safety risk profile.
Credit Suisse's Michael Aberman, in a note to clients, wrote, "Ultimately, we are not certain how these cases of heart failure impact will impact the regulatory and commercial outlook for darusentan but believe that the edema and cases of heart failure increases the risk. While we believe darusentan will be approved for resistant hypertension, the commercial potential is limited given its side effect profile and the genericized market."
Mark Schoenebaum, the biotech analyst at Deutsche Bank, told his clients, "Resistant hypertension patients are, by definition, at increased risk for heart attacks & heart failure. Thus, such events would be expected in this population. That said, the imbalance between darusentan and placebo in this relatively small trial (despite the lack of statistical signficance) does raise some concerns."
Gilead is best known for its market-leading HIV drug franchise, but more recently the company has sought to diversify into other disease areas, including cardiovascular disease. This includes Gilead's decision in March to acquire CV Therapeutics and its chronic angina drug for $1 billion.
A second phase III study of darusentan is expected to be completed by the end of the year.
Other companies with drugs to treat various forms of high blood pressure include
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