Almost a year after Neurochem Inc. received its first approvable letter for Kiacta (eprodisate) in the treatment of AA amyloidosis, history repeated itself.
The Laval, Quebec-based company said late Tuesday that its wholly owned subsidiary, Neurochem Ltd., received a second approvable letter for the drug. Just as before, Neurochem will attempt to address the FDA's concerns without conducting another clinical trial, but analysts remain skeptical about both Kiacta and Neurochem's Phase III Alzheimer's drug Alzhemed (tramiprosate).
This skepticism appears to be shared by investors, who have pushed the stock price down from about $26 last fall to a 52-week low of $5.01 on Tuesday. Shares of Neurochem (NASDAQ:NRMX) dipped 60 cents on Tuesday but rose 11 cents on Wednesday to close at $5.40.
Kiacta's woes date back to a Phase II/III clinical trial that missed its primary endpoint of stabilizing or improving AA amyloidosis patients with impaired renal function. The 24-month, 183-patient trial needed 20 percent more patients in the Kiacta group than the placebo group to reach the endpoint with a p-value of 0.01. Instead, only 13.4 percent more Kiacta patients met the endpoint with a p-value of 0.06. (See BioWorld Today, April 19, 2005.)
Neurochem decided to file for approval anyway, but received an approvable letter in mid-2006 asking for efficacy data as well as information about manufacturing, pharmacokinetics and a plan for a post-approval QT clinical study. Rather than address the efficacy concerns with another clinical trial, Neurochem elected to re-analyze its existing data and submit updated data from an ongoing open-label trial. (See BioWorld Today, Aug. 15, 2006.)
A year later, the second approvable letter looks much like the first, requesting a new efficacy trial with a target p-value of 0.05 as well as further pharmacokinetic studies and plans for the post-approval QT clinical study. And much like last time, Neurochem plans to compile a consolidated report of all data provided to date as well as a safety update rather than initiating a new clinical trial.
"It sounds like not a lot has changed as far as the FDA's stance," said Brian Lian, analyst with CIBC World Markets Corp. He added that it seems "highly unlikely" that Kiacta will gain approval without another trial.
Lise Hébert, vice president of corporate communications at Neurochem, said it should take about two months to gather the new analyses for the FDA. As to whether or not Neurochem would conduct a new trial if the re-analysis fails, she answered with a cryptic "we will see," but noted that the FDA has offered to assist the company in designing such a trial.
Regardless, Jonathan Aschoff, analyst with Brean Murray, Carret & Co. LLC, called the Kiacta program "dead in the water." In a research report, he said the Phase II/III trial was a "complete failure" and that "there is no additional useful data that could possibly be included in a future Complete Response."
Kiacta also is under regulatory review in Europe, where a decision is expected in late 2007 or early 2008, and in Switzerland, where a decision may come in early 2008. Hébert said the company will continue to run the open-label study until a regulatory decision is made so that AA amyloidosis patients can have access to the drug. There are no approved treatments for the disease, which affects patients with chronic inflammatory disorders, chronic infections and inherited diseases, resulting in renal disease and potentially death.
Kiacta is partnered with Malvern, Pa.-based Centocor Inc., which has exclusive worldwide distribution rights, except for Canada, Switzerland, Japan, China, South Korea and Taiwan.
Beyond Kiacta, Neurochem also may be in trouble with its Phase III Alzheimer's drug, Alzhemed. The company locked the database for its completed Phase III U.S. clinical trial in April but keeps postponing the release of any data. The latest estimate is that data would be available in the second half of this year.
Lian said it is "not clear" why the analysis is taking so long, but that "most people think the trial failed." Aschoff predicted the trial will show "essentially no difference between the drug and the placebo arm."
A follow-on study with Alzhemed is ongoing in the U.S., and a Phase III study in Europe continues enrollment.
Neurochem's only other drug, Cerebril (tramiprosate), completed a Phase IIa trial in hemorrhagic stroke due to cerebral amyloid angiopathy but was put on the back-burner as resources were diverted to the two lead programs.
Neurochem reported $35.5 million in cash, equivalents and marketable securities at the end of the first quarter and completed an $80 million private placement in June. Lian said the fact that they did the financing before announcing the Alzhemed data is not encouraging.
Aschoff called the company essentially a SPAC, or management team with money but no products, with memories.