News that Amarin’s fish-oil pill AMR101 hit its primary endpoints in the first of two pivotal trials in patients with high triglycerides sent shares in the Irish-American group rocketing 60% higher in early trading today to a three-and-a-half year high of $5.74. Investors are beginning to ascribe significant value to a drug that has the potential to equal the blockbuster Lovaza in efficacy, without the side effect of raising low-density lipoprotein (LDL), the so-called “bad cholesterol.”
The Marine trial of AMR101 is reporting a year earlier than expected, and the failed Huntington’s disease drug is now wowing investors and analysts in the competitive and risky cardiovascular space. The company believes itself to be in a rather comfortable position: sufficiently funded to achieve a filing with US regulators on its own and at the same time entertaining partnership discussions from a dozen big pharma suitors. With a market value approaching $600m, expectations for Amarin are growing fast.
Variation on a theme
Lovaza and AMR101 both contain prescription grade omega-3 ethyl esters, the same compounds sought by those who take fish-oil pills for cardioprotective reasons. The main difference between the two is that AMR101 contains almost no docosahexaenoic acid (DHA), thought to be the culprit in the elevated LDL with Lovaza.
The Marine study reporting today tested AMR101 (ethyl icosapentate, or EPA) against placebo in patients with greater than 500mg triglycerides per decilitre of blood. In patients taking 4 grams per day of AMR101, a median decrease of triglycerides of 33% was recorded, and in patients taking 2 grams per day the decrease was 20%.
Investigators detected no statistically significant increase in LDL. In a subgroup of patients with very high triglycerides the decrease was 45% among those taking 4 grams per day and 33% in those taking 2 grams per day, and those on statins also saw a decrease in triglycerides.
The pivotal trials for Lovaza, also known as Omacor, showed a greater median decrease in triglyceride levels - 44.9% - but also started from a higher median baseline of 816 milligrams per deciliter of blood, compared with the 680 in the patients treated with 4g per day of AMR101 and 657 in the 2g per day group. In the subgroup of patients with very high triglycerides of greater than 750 mg/dL in the Marine trial, the group looked similar to the Lovaza trial - 902 mg/dL for those taking 4g per day and 948 mg/dL in the 2g group - suggesting at least equal efficacy for AMR101.
The company awaits news on the second pivotal trial, called Anchor, which tests AMR101 plus statins against placebo plus statins in patients with high triglyceride levels, defined as those with between 200mg and 500mg per decilitre.
In an interview today with EP Vantage, company president John Thero said inclusion of the effects on LDL was less essential in the population tested in the Marine trial than in the Anchor trial, where an increase of 6% in LDL levels would result in an increase in statin dosage.
“To the extent that there is a readthrough is that there is confirmation that EPA does lower triglycerides in a significant way and that there is confidence that in the Marine study there was no increase in LDL,” Thero said. “It’s notable in the Marine study that for patients who are on statin our drug performed as well or better than it did in the patients not on statin.”
EvaluatePharma’sconsensus estimates sales of $552m by 2016. This results in a net present value of $1.25bn for Amarin, still well above its new inflated market capitalisation. It should be noted however that Amarin expects to partner the drug for commercialisation, so it will likely collect only a portion of sales for AMR101.
Some analysts are estimating peak sales as high as $2bn and setting price targets as high as $7, a value the company is coming close to realising with today’s stock jump.
The company notes that with $31.4m as of September 30 it has sufficient cash to complete the current trials and file with the FDA. It is considering marketing the drug itself if necessary, although that would require fundraising, and partnership remains the strategy for now.
After disappointment as a central nervous system drug, AMR101 has exceeded expectations in its first pivotal cardiovascular trial. A second confirmatory test in the population taking statins would likely raise hopes even higher that Lovaza, sales of which are forecast to tip the magical $1bn mark next year, has stiff competition on its hands.
|Clinical trial ID||NCT01047683|