MYSTIC, Conn.—With positive results to announce in the early morning from its Phase III trial, dubbed MARINE, for its potential fat-lowering drug AMR101, Amarin Corp. saw its shares rise as much as 20 percent in trading before Nasdaq started its day on Nov. 29. Moreover, the news was not only good enough to drive the stock price up but also the hopes of Amarin management, as the company announced that it would ask the U.S. Food and Drug Administration to approve the medicine next year, ahead of the company's original forecast of a 2012 submission.
As such, Amarin is potentially poised to compete directly with GlaxoSmithKline's Lovaza, which like AMR101 is an omega-3 fatty acid-based drug. So far, Lovaza is the only omega-3-based prescription drug approved in the United States, and it generated $703 million in sales there for GSK last year.
In the MARINE study, patients with triglyceride levels of more than 750 milligrams per deciliter of blood who were given a four-gram dose of AMR101 saw the blood fat reduced by 45 percent compared with patients taking a placebo, while those who took a dosage half that still saw a reduction of 33 percent. This is the first of two final-stage studies focused on patients with very high triglyceride level; the second study, ANCHOR, is likely to finish enrolling 650 patients before Christmas, according to Amarin, and results of the study are expected next year.
One of the notable aspects of AMR101 is that according to study results thus far, it doesn't significantly increase low-density- lipoprotein cholesterol, although similar treatments may raise cholesterol by as much as 50 percent in patients with high triglycerides, says Harold Bays, medical director at Louisville Metabolic and Atherosclerosis Center and principal investigator of the study. This could distinguish Amarin's drug from GSK's, as Lovaza's risk of increasing levels of low-density lipoprotein (LDL) cholesterol pretty much restricts its use to patients with very high baseline triglyceride levels. Another point of distinction is that AMR101 seems to be able to get comparable triglyceride reductions with a lower milligram-per-deciliter dosage.
"The MARINE study was conducted in a population representative of millions of people with very high triglyceride levels, including more than 3.8 million in the U.S. alone. We believe that these results and the overall profile of AMR101 position the drug candidate to be best in class in this market," says Joseph Zakrzewski, executive chairman and CEO of Amarin.
Analyst consensus right now is that if the other Phase III trial shows good results as well, Amarin will at the very least probably seek a partner for commercializing AMR101, or seek to be bought out entirely by a larger pharma.
Despite the upbeat news, risks remain, as noted by Canaccord Genuity analyst Ritu Baral, who pointed out that if the ANCHOR trial shows even a low LDL increase, AMR101 may not be approved for mixed dyslipidemia and use with statins:
"Cholesterol experts and FDA are very focused on omega-3's impact on LDL levels and subsequent heart risk. We note that that there is a chance that AMR101 may have a higher-than-acceptable elevation in LDL, despite a sizeable body of data that suggests it may have a smaller impact on LDL levels than Lovaza," Baral says. Also, he notes, looking at the regulatory risk, the FDA may not feel the status of the required outcomes study is sufficiently
advanced.
"FDA required Amarin in an SPA to have an outcomes study 'substantially underway' as a prerequisite for AMR101 approval for mixed dyslipidemia, but the exact requirement is not clear," Baral says. "Should FDA be unsatisfied with Amarin's progress in the outcomes study at the time of NDA filing, the agency may delay approval for this patient population."
Also, Baral adds, Amarin may not partner AMR101 as planned.
"We think that AMR101 is a differentiated drug with a compelling scientific rationale and considerable market potential. opportunity. We believe Amarin has an experienced business development team that will likely be able to establish a partnership with rich terms to Amarin," Baral says. "However, we think the timing and terms of such partnerships can be difficult to predict."
As such, Amarin is potentially poised to compete directly with GlaxoSmithKline's Lovaza, which like AMR101 is an omega-3 fatty acid-based drug. So far, Lovaza is the only omega-3-based prescription drug approved in the United States, and it generated $703 million in sales there for GSK last year.
In the MARINE study, patients with triglyceride levels of more than 750 milligrams per deciliter of blood who were given a four-gram dose of AMR101 saw the blood fat reduced by 45 percent compared with patients taking a placebo, while those who took a dosage half that still saw a reduction of 33 percent. This is the first of two final-stage studies focused on patients with very high triglyceride level; the second study, ANCHOR, is likely to finish enrolling 650 patients before Christmas, according to Amarin, and results of the study are expected next year.
One of the notable aspects of AMR101 is that according to study results thus far, it doesn't significantly increase low-density- lipoprotein cholesterol, although similar treatments may raise cholesterol by as much as 50 percent in patients with high triglycerides, says Harold Bays, medical director at Louisville Metabolic and Atherosclerosis Center and principal investigator of the study. This could distinguish Amarin's drug from GSK's, as Lovaza's risk of increasing levels of low-density lipoprotein (LDL) cholesterol pretty much restricts its use to patients with very high baseline triglyceride levels. Another point of distinction is that AMR101 seems to be able to get comparable triglyceride reductions with a lower milligram-per-deciliter dosage.
"The MARINE study was conducted in a population representative of millions of people with very high triglyceride levels, including more than 3.8 million in the U.S. alone. We believe that these results and the overall profile of AMR101 position the drug candidate to be best in class in this market," says Joseph Zakrzewski, executive chairman and CEO of Amarin.
Analyst consensus right now is that if the other Phase III trial shows good results as well, Amarin will at the very least probably seek a partner for commercializing AMR101, or seek to be bought out entirely by a larger pharma.
Despite the upbeat news, risks remain, as noted by Canaccord Genuity analyst Ritu Baral, who pointed out that if the ANCHOR trial shows even a low LDL increase, AMR101 may not be approved for mixed dyslipidemia and use with statins:
"Cholesterol experts and FDA are very focused on omega-3's impact on LDL levels and subsequent heart risk. We note that that there is a chance that AMR101 may have a higher-than-acceptable elevation in LDL, despite a sizeable body of data that suggests it may have a smaller impact on LDL levels than Lovaza," Baral says. Also, he notes, looking at the regulatory risk, the FDA may not feel the status of the required outcomes study is sufficiently
advanced.
"FDA required Amarin in an SPA to have an outcomes study 'substantially underway' as a prerequisite for AMR101 approval for mixed dyslipidemia, but the exact requirement is not clear," Baral says. "Should FDA be unsatisfied with Amarin's progress in the outcomes study at the time of NDA filing, the agency may delay approval for this patient population."
Also, Baral adds, Amarin may not partner AMR101 as planned.
"We think that AMR101 is a differentiated drug with a compelling scientific rationale and considerable market potential. opportunity. We believe Amarin has an experienced business development team that will likely be able to establish a partnership with rich terms to Amarin," Baral says. "However, we think the timing and terms of such partnerships can be difficult to predict."
