Replies to post #3516 on Arena Pharmaceuticals, Inc. (ARNA)

[Kev2128]

What reviewers?

[foodcourt1]

The news is out! It seems ...CRAP! My crystal ball just slipped from my hands and shattered all over my kitchen floor! damn, i hate when that happens. Guess we all have to wait till thursday. Good luck to all.

[lovethatgreen]

Pulled from the Murphy article

23 cardiologists participated in the testing trials( from the citizens petition)

Valvulopathy was the issue that caused fenfluramine to be removed from the market. Arena did periodic heart scans on every patient in their clinical trials to check for valvulopathy. The company initally wanted to exclude the possibility that Lorqess doubles valvulopathy. The FDA wanted them to exclude a 50% increase. Assuming the “normal” incidence of valvulopathy would be 2.5%, they set the trial size at 8,000 patients to meet the FDA requirements.

But the incidence of valvulopathy was only 1.7%, so the company can only exclude an increase of 67%, not 50%. They might have had to do another 4,000 patients to exclude a 50% increase in valvulopathy at that surprisingly low level of incidence.

FDA Deputy Director Eric Colman said in the last Advisory Committee meeting that the 50% exclusion is a fluid standard. But – here’s the point – lorcaserin does not CAUSE valvulopathy. The exclusion statistics are just a matter of statistics and sample size. There was no increase in valvulopathy in the Phase III trials. The company has done further work in response to the CRL on the affinity of lorcaserin for the serotonin 2A or 2B heart receptors (very low) versus the serotonin 2C appetite receptor (very high), and the transient nature of valvulopathy in the trials plus the fact that there was no particular increase in overall valvulopathy all tell the panelists that valvulopathy is not a problem. At most, Arena may be required to monitor the first 2,000 or 4,000 patients for valvulopathy post-approval, just to reassure the FDA.