SCH-C Moves Ahead -- Carefully
Schering Plough held a meeting to update community members about the progress of the company's novel CCR5 inhibitor, SCH-C, which is moving through the first phases of clinical development. The pace of testing has been slowed because of cautions put in place by the FDA after transient electrical abnormalities were detected in the heart rhythms of three patients receiving SCH-C at high doses. The abnormality, a prolongation of the QTc interval, indicates an event when the heart is signaled to beat before the muscle is fully prepared to contract. This condition can possibly result in the heart losing its ability to move blood, with sudden death the outcome. Because of this potentially catastrophic consequence, the FDA has asked for close monitoring of patients receiving SCH-C until the significance of this observation is clarified. Patients entering the phase Ib trial will probably be observed for a week or so under constant telemetry in a medical facility to assure that any arrhythmias are safely detected and corrected.
Interestingly, very little is currently known about the normal prevalence of QTc prolongation among the background population; indeed, in the SCH-C study, 3 of 18 patients receiving placebo also experienced abnormal QTc. Yet prudence (and the FDA) demands that early studies of this promising drug proceed carefully and deliberately.
As expected, Triangle Pharmaceuticals has submitted data on its nucleoside analog FTC (Coviracil) to the FDA for approval. They should hear in a month or so if it will receive a priority review. But this good news was preceded by a report that one of the company's other drug candidates, DAPD, has received a go-slow order from the FDA because of some belatedly noted findings on the lenses of the eyes of trial participants. The drug is a nucleoside analog with the attractive potential to remain active against virus resistant to AZT and 3TC (and FTC?). During animal testing at extremely high doses, the drug crystallized in the kidneys, which set off a cascade of toxic events that included development of corneal opacities. On the basis of this finding, the company added opthalmologic testing to their ongoing clinical studies. In a few people, investigators reported finding minor lens abnormalities, although no evidence of kidney toxicity that would have precipitated them. Since there were no baseline eye tests, it's unclear at this point what significance these pinpoint spots have, if any, since similar lens abnormalities tend to become common with increasing age and UV exposure. But once again, in the interest of safety, the FDA has asked that new enrollments into the ongoing trials be temporarily held until more thorough baseline screening procedures can be put in place.
Although this latest situation is probably not drug-related, Triangle has had a long string of bad luck with its attempts to get an AIDS drug into the market. But you can't say they're dodging the reality of their situation. The company's Web site (www.tripharm.com
) prominently features a list of "risk factors" on its front page that makes for chilling reading. Check it out.
Hepsera (Adefovir for HBV)
Gilead Sciences, having failed in its attempt to launch adefovir dipivoxil as an HIV drug due to kidney toxicity at necessary doses, regrouped its forces and is on the verge of seeing the drug approved -- at a much more tolerable dosage -- for treating chronic hepatitis B infection. The company announced that it has selected Hepsera(TM) as the U.S. trade name for adefovir. Approval should be granted by the time you read this.