January 3, 2013
Paul E. Sax, M.D., is director of the HIV Program and Division of Infectious Diseases at Brigham and Women's Hospital in Boston.
As Physician's First Watch noted, we sure know what the folks at the FDA were doing this holiday season -- and most emphatically they weren't visiting Aunt Selma in Boca Raton.
Nope, they were stuck in White Oak, Maryland, reviewing various new drug applications, with three of the four related to Infectious Disease. The FDA's late 2012 actions:
For crofelemer, according to the FDA announcement, approval was based on the results of a phase III, double blind study comparing 125 mg of crofelemer twice daily to placebo in HIV patients with non-infectious diarrhea:
The trial was designed to measure clinical response, defined as the number of patients who had two or fewer watery bowel movements weekly. Results showed that 17.6 percent of patients taking crofelemer experienced clinical response compared with 8 percent taking placebo.
Further information on the drug -- including its mechanism of action and nifty source, "the Croton lechleri plant, native to northwestern South America" -- can be found on the company's website.
I confess this approval took me by surprise. I was aware that crofelemer was in clinical trials, but hadn't heard a peep about it at scientific meetings or other venues. Obviously some of this low profile is due to the fact that it's not an antiretroviral agent, but compared with the attention given to tesamorelin, this is certainly a stealth approval.
Notably, current HIV medications are far less likely to cause diarrhea than the first generation of meds. The big offenders -- ddI, full-dose ritonavir, nelfinavir, amprenavir, soft-gel saquinavir, even lopinavir/r -- are today used either infrequently in the United States or not at all. (Several are not even available.) I assume that clinicians who have patients with ongoing diarrhea on any of these agents would switch antivirals first rather than starting a new medication for the side effect.
So who are the appropriate candidates for this drug? Even after switching off older HIV meds, some patients will continue to have diarrhea, either still due to the medications -- most notably the PI's with ritonavir -- or from "HIV enteropathy", which is damage the virus has done to the GI tract which in some people reverses very slowly, or not at all. For them, this approval gives them a welcome new option.
Plus, we get a sparkling new brand name to learn, and to make jokes about. This one's a doozy -- Fulyzaq!
So who came up with that? See above for an artistic rendition of a Fulyzaq in the wild.
Paul Sax is Clinical Director of Infectious Diseases at Brigham and Women's Hospital. His blog HIV and ID Observations is part of Journal Watch, where he is Editor-in-Chief of Journal Watch AIDS Clinical Care.