Biotech Values

[DewDiligence]

Cangrelor Can Still Succeed—Maybe

[These are post-hoc subset data subset data from the two phase-3 Cangrelor trials in PCI that were stopped in May 2009 by the DSMB due to futility: one tested Cangrelor vs Plavix and the other tested SoC ± Cangrelor (#msg-37803743). The comments below from the PI of one of the two failed trials strike me as unduly bullish on the drug’s prospects.]

http://www.reuters.com/article/marketsNews/idCNN1518391020091115

›Sun Nov 15, 2009 2:22pm EST
By Ransdell Pierson and Bill Berkrot

ORLANDO, Fla., Nov 15 (Reuters) - An experimental Medicines (MDCO) Co blood thinner that failed two late-stage clinical trials earlier this year still holds great promise and deserves to be tested in new studies, researchers said on Sunday.

The company discontinued two large trials of the intravenous drug, called cangrelor, in May after an independent monitoring board deemed it unlikely to prove to be superior to the widely used pill Plavix.

Cangrelor had been tested against Bristol-Myers Squibb Co's (BMY) Plavix among patients undergoing procedures to clear their heart arteries of plaque, to see if it was better within 48 hours at reducing incidence of death, heart attack or a need for new heart procedures.

Cangrelor failed the trials because it was not satisfying that combination of study goals, or endpoints. Even so, it sharply reduced overall mortality and the occurrence of blood clots associated with new stents, researchers said.

Some 0.7 percent of patients taking Plavix by itself died within 48 hours of treatment, compared with 0.2 percent of those who received cangrelor in combination with Plavix, representing a 67 percent reduction for the cangrelor group.

Clotting from stents was reduced from 0.6 percent in the Plavix group, to 0.2 percent of those taking both cangrelor and Plavix, and the reduced clotting may help explain the lower death risk, researchers said.

The data were presented at the American Heart Association scientific meeting in Orlando.

Dr. Deepak Bhatt, chief of cardiology at the Veterans Administration Boston Healthcare System -- who helped lead one of the two large failed trials -- said he believes Medicines Co will likely conduct new big trials of cangrelor in view of the favorable secondary data on survival and stent blood clots.

"I think it should be tested again in large Phase III trials because there is a clinically meaningful benefit" in those secondary trial goals, even though the earlier studies failed to achieve their combined main goals.

Bhatt and other researchers said cangrelor may post better results if patients receive longer intravenous infusions, should new trials commence.

He said an older clot preventer, Merck & Co's (MRK) Integrilin, failed initial trials only to succeed in later studies after its dosage was increased.

Cangrelor belongs to a newer class of agents that includes Plavix, Eli Lilly's (LLY) Effient and AstraZeneca Plc's (AZN) Brilinta. They use the same mechanism to prevent blood cells called platelets from clumping together to form clots, and all are pills, with the exception of cangrelor.

"Cangrelor is the only intravenous one of them, which becomes an appealing feature when patients can't take pills because they are vomiting, or are on a ventilator or sedated," Bhatt said.

Moreover, he said cangrelor takes effect very quickly and unlike Plavix, its blood-thinning effects can be quickly reversed if doctors need to perform major surgery.

An editorial in the New England Journal of Medicine suggested that the failure of the earlier studies may have been due more to trial design than to a failure of cangrelor, which it called a potent medicine "with rapid onset and offset of action."

"These valuable qualities certainly warrant further study aimed at identifying more suitable clinical niches for cangrelor and more appropriate approaches to its use," the editorial concluded.‹