Amicus Shelves New-Drug Filing For Fabry Disease Drug

Xconomy New York — 

[Updated, 1:10 ET] Investors are going to have to wait awhile before they see Amicus Therapeutics submit its Fabry Disease drug to the FDA for approval. And they immediately showed their displeasure by sending the Cranbury, NJ-based company’s stock down more than 20 percent.

John Crowley, Amicus’ CEO, said on a conference call Monday that following discussions with the FDA, Amicus (NASDAQ: FOLD) has decided the data from its late-stage clinical trial of migalastat HCl isn’t enough to get the drug approved. Instead, Amicus will complete that study, as well as another ongoing Phase 3 trial before filing a new drug application (NDA) with the FDA.

While that doesn’t mean migalastat is done as a potential treatment for Fabry, it does mean the verdict won’t be known for some time. With the crucial data expected in the second half of 2014, Amicus could be looking at 2015 before having a chance to win FDA approval.

[Updated with CEO comment] “We are essentially trading time for certainty,” Crowley tells Xconomy. “Looking at all that data that’s going to come, I think it’ll make for a pretty compelling data package if the data keeps trending the way that we’ve seen before.”

Investors weren’t thrilled. Shares plunged 20 percent to $2.53 apiece as of 10:08 ET, from a $3.19 Friday close.

Those investors are understandably skeptical. Amicus’ drug for Gaucher Disease failed in clinical trials in 2009, and in December, Amicus said that the Fabry drug didn’t hit the main goal of its late-stage study after a six-month period.

But Amicus believes that once all of its studies run their course—the Fabry study will conclude after two years of total data—the skeptics will be proven wrong.

“We believe that the better regulatory strategy is to obtain all of the Phase 3 datasets and to combine and integrate these data into one NDA submission,” Crowley said on the call.

Fabry is a rare inherited disease that affects between 5,000 and 10,000 people worldwide. It’s caused by the deficiency of a specific enzyme that breaks down a fat known as globotriaosylceramide (GL-3). Without the enzyme, GL-3 builds up in blood vessels, causing a host of side effects including severe kidney damage.

Fabry is currently treated with enzyme-replacement therapies, such as agalsidase (Fabrazyme), which are administered intravenously. Amicus’ drug is a pill. Agalsidase, sold by Sanofi/Genzyme, is the only drug approved to treat Fabry in the U.S.

Amicus has two late-stage trials going. In the first trial, 60 patients were broken into two equal-sized groups and randomly given either migalastat or a placebo. The placebo group was then transitioned to migalastat after six months.

At the end of the year, patients are given an option to continue therapy for an additional year (Crowley said 57 of those patients elected to do so).

In the second 60-patient study, 36 patients already undergoing enzyme-replacement therapy switched over to megalistat; the other 24 stayed on their existing therapy. Amicus is collecting data from that study over 18 months, and hopes to show that migalistat isn’t inferior to enzyme-replacement therapy, Crowley said on the call.

Amicus met with the FDA following the disappointing six-month results from its first study, which showed that 41 percent of the patients taking its drug met the study’s goal—to reduce GL-3 levels by 50 percent—while 28 percent of the placebo group did. Amicus said that difference wasn’t statistically significant.

Amicus proposed revisions to the study to the FDA based on reviewing the drug’s impact over 12 months, for example, but the agency indicated that wouldn’t help Amicus’ case for approval. Amicus hasn’t yet seen the 12-month data, Crowley said on the call.

The FDA said it would review the drug based on the “entirety” of the clinical data the two late-stage studies, and agreed to a follow-up meeting after the 12-month data is available and the second Phase 3 study is completed, he said.

[Updated with CEO comments] Crowley also points out that Amicus has shown in mid-stage trials both in Fabry and Pompe that its drugs can improve the effectiveness of enzyme-replacement therapies when used in concert with them, and that it has a “next generation” enzyme-replacement therapy for Fabry in preclinical development that is already partnered with GlaxoSmithKline that will begin clinical trials in early 2014.

“We really get no credit for that—quite frankly looking at today’s stock market today I don’t think we get credit for much beyond our cash,” Crowley says.

Amicus had about $85 million in cash on hand at the end of the first quarter, and while Crowley says that is enough to get Amicus through the second half of 2014, the company has already been exploring potential partnerships to help bring in revenue without diluting its stock. Amicus has a drug for Pompe disease, an enzyme-related muscle disorder, in mid-stage clinical trials, and a pre-clinical drug for Parkinson’s disease, both of which it owns all the rights to. Crowley says Amicus has already had discussions about partnerships for both, and could attempt to structure deals for those individually, or for its platform for creating next-generation enzyme-replacement therapies as a whole.

“We’ll be open to lots of potential business development transactions in the quarters to come,” Crowley says.

For the Pompe drug, Amicus would look to do something “that would mirror” its partnership with GlaxoSmithKline: Amicus would keep U.S. rights, give up international rights, and the partner would take on the majority of the development costs. For the Parkinson’s drug, Amicus would be “less insistent” on keeping marketing rights, and would be more apt to trade potential royalties and milestone payments for a share in the development expenses, according to Crowley.

Crowley said on the call that the British pharma giant is still fully invested in its partnership with Amicus. GSK is Amicus’ largest shareholder and held 19.8 percent of its stock as of April 26, according to a proxy filed with the Securities and Exchange Commission.