La Jolla falls on mixed results for shock treatment
- Mixed results from a Phase 3 study of La Jolla Pharmaceutical's experimental treatment for a life-threatening type of shock sent shares in the San Diego biotech down more than 5% Monday morning.
- Results from a primary analysis of the ATHOS-3 study showed La Jolla's angiotensin II reversed low blood pressure within three hours of treatment compared to placebo, meeting the study's primary endpoint.
- But the drug did not improve total organ function or significantly reduce all-cause mortality at one to four weeks following treatment, although the study showed a numerical improvement. While success in meeting the trial's objective likely means the drug will win U.S. approval, the weaker results on organ function and death could cloud prospects for future commercial success.
Investor expectations were primed last week, after trading in La Jolla stock was halted Thursday. The company filed an update with regulators announcing the ATHOS-3 results would be published Sunday, sending shares sharply higher by 24% at Thursday's close.
But shares in the company fell back Monday after full results were disclosed.
Angiotensin II is designed to increase blood pressure for patients suffering from vasodilatory shock, a dangerous condition where blood pressure falls despite adequate cardiac function. Organ failure can result due to decreased flow of oxygen.
Current treatment options include vasopressor drugs such as catecholamine or vasopressin, but a substantial number of patients develop vasodilatory shock that is resistant to catecholamine. According to La Jolla, more than half of those patients die within 30 days.
In its release Sunday, La Jolla touted the drug's success on its primary endpoint. Angiotensin II significantly raised blood pressure in nearly 70% of patients, compared to only 23% of those treated with placebo.
However, both treatment and placebo groups saw a one point mean increase in total SOFA score at hour 48. SOFA scores, which measure organ function, range from 0 to 4, with higher scores indicating greater dysfunction.
Patients receiving angiotensin II did see a statistically significant improvement in cardiovascular SOFA score, a subset of the total measure. And while treatment showed "a trend toward longer survival" as measured by all-cause mortality at day 7 and day 28, the results were not statistically significant.
"With positive primary outcome, we continue to view FDA approvability as high," Eun K. Yang, an analyst at Jefferies, wrote in a May 22 note. "However, given lack of [statistically significant] mortality benefits [and] total organ function improvement (except for catecholamine use reduction), its commercial potential could be debatable."
Fewer patients discontinued angiotensin II due to adverse events versus placebo, and overall adverse event levels were lower in the treatment arm. Rates of infection and delirium were higher for angiotensin II, however.
Lack of an effective treatment for catecholamine-resistant shock will likely help La Jolla and could boost the drug's chances with the Food and Drug Administration. However, the lack of significant secondary endpoint data could make marketing more difficult if an approval is secured.
La Jolla has one other drug in clinical development, LJPC-401 (synthetic human hepcidin), which is expected to move into a pivotal Phase 2 study in iron overload in mid-2017.
- La Jolla Pharmaceutical Press release
- NEJM Angiotensin II for the treatment of vasodilatory shock
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