4 IN. DI LETTURA
(Recasts; adds comments from analysts and companies, background; updates share movement)
By Esha Dey
BANGALORE, April 25 (Reuters) - Isis Pharmaceuticals ISIS.O will delay submitting final results from a late-stage study of its cholesterol drug after U.S. health regulators asked for additional cancer-related data from two preclinical trials, sending its shares tumbling 30 percent.
Isis and co-developer Genzyme Corp GENZ.O expect to submit final data from the ongoing late-stage trial of the drug, mipomersen, in 2010. Earlier, submission was expected in 2009, Isis spokeswoman Amy Blackley said.
"It is clear that the time line has shifted significantly to the right and development risk and expense have increased," Leerink Swann analyst Joseph Schwartz said in a note to clients. Schwartz kept a "market perform" rating on Isis.
Mipomersen reduces the production of a protein critical to the synthesis and transport of low-density lipoprotein (LDL) or "bad" cholesterol.
The companies are studying the drug in patients with a rare genetic disorder, known as familial hypercholesterolemia (FH), characterized by high "bad" cholesterol.
The clinical studies are being held for two types of FH, homozygous and heterozygous. The U.S. Food and Drug Administration said that reduction of low-density-lipoprotein (LDL)-cholesterol is an acceptable "surrogate endpoint" for accelerated approval of mipomersen in patients with homozygous FH, Isis said.
The drug meeting the "surrogate" goal of reducing LDL-cholesterol levels would not be sufficient to get an approval, Leerink Swann's Schwartz said by phone. "You need hard outcome," he added.
Isis spokeswoman Blackley said that LDL-cholesterol reduction was the main goal of the ongoing late-stage trial in homozygous FH.
The company's pipeline consists of 19 "antisense" drugs, which seek to treat genetic disorders or infections.
Isis currently has only one drug, Vitravene, in the market. Vitravene treats a condition called cytomegalovirus (CMV) retinitis -- which causes the inflammation of the eye's retina -- in people with AIDS.
Shares of Isis fell to a low of $11.68, before recovering slightly to trade down $4.50 at $12.30 Friday afternoon on Nasdaq.
The company was expecting to file the results from the heterozygous FH study in 2011, Isis spokeswoman Blackley said.
J.P. Morgan analyst Geoffrey Meacham said, "The filing of mipomersen in heterozygous FH will now require a cardiovascular outcomes study, which introduces substantial clinical risk and likely results in a filing delay to 2012."
There will be more delays and uncertainties related to the drug in the future, Needham & Co analyst Mark Monane said by phone. He downgraded the stock to "hold" from "strong buy."
"There is uncertainty regarding the terms of the Isis-Genzyme collaboration, which was announced in January 2008 but has not been signed, sealed and delivered," Monane added.
Genzyme spokeswoman Erin Emlock said the company's collaboration with Isis stands, but declined to comment on whether the terms of the deal may be changed.
Isis and Genzyme plan to conduct an outcome trial for the drug, and are revising the development plan for mipomersen, they said in a joint press release.
Genzyme shares, which fell to a low of $72, were trading down almost 1 percent at $72.66 Friday afternoon on Nasdaq. (Editing by Pratish Narayanan)