AMRN – Update on Amarin’s AMR101 as PDUFA date draws closer

Amarin Corp (NASDAQ: AMRN) released first quarter 2012 financial results and held a conference call on May 8, 2012. It is often hard to distinguish the signal from the noise when it comes to chatter about AMRN on Twitter and other venues, so we will try to objectively update where things stand as the July 26, 2012 PDUFA date for the approval of AMR101 to treat patients with very high triglyceride levels (also known as the MARINE indication based on the name of the phase 3 trial in this population).
Previous AMRN coverage:

Notes from Citi Global Healthcare Conference presentation (subscribers only)

Notes from Leerink Swann Global Healthcare Conference presentation (subscribers only)

Analysis: Will AMR101 receive New Chemical Entity (NCE) status from the FDA? (This post is freely available to all and happens to be the most popular post ever on the BiotechDueDiligence blog. I originally authored this article in November 2011, but the facts and my opinions have not materially changed since then)


Pending New Drug Application with July 27, 2012 PDUFA date:

As I first flagged in February based on management comments at the Citi conference (see link above), Amarin has been continually telegraphing that there is a reasonable chance of a 3-month delay in the PDUFA date for AMR101. This could be triggered by requests for additional information or data by the agency (such a request would automatically result in a delay if it occurs within 90 days of the PDUFA date). Alternatively, a delay could arise from the Chemistry, Manufacturing, and Controls (CMC) section of the NDA. AMR101 involves a complex purification and manufacturing process spread out across multiple global suppliers. On the conference call, management dodged the question of whether the API supplier had passed inspection, giving only the useless response that the inspections that one would expect to have taken place by this time in the process have occurred.

New Chemical Entity (NCE) Status:

See the link above for a detailed discussion. Due to the allowance of the ‘598 patent (EPA with no DHA in a capsule)  in March 2012, management has begun downplaying the significance of receiving 5-year NCE marketing exclusivity. We agree that this is a fair perspective, and with the assertion that receiving 3 years exclusivity is all but assured. Amarin remarked that even the three-year window would give a substantial time frame to strengthen the rest of the intellectual property portfolio. The company pointed out that the decision on NCE status will most likely be revealed around the end of the month after approval when the drug’s Orange Book listing is published.

The “Three Paths” – buyout, partnership, or launching the product:

There was nothing new to report on this front. Amarin continues to consider all three possibilities, and we continue to believe any strategic transaction is highly unlikely before FDA approval. A question was asked about the impact that the patent allowance had on these discussions, but the long-winded answer yielded no actual response.

Expansion of supply chain and market opportunities:

The pending NDA only covers the treatment of patients with triglyceride levels about 500 mg/dL with AMR101 product made by a single API supplier. Broadening the supply chain via additional API suppliers (Amarin indicated they will announce a 4th in 2012) and the market opportunity via the 250-499 mg/dL indication (based on the ANCHOR clinical trial) will require supplementary filings known as sNDA’s. On the call, Amarin indicated that additional supplier filings could occur in 4q-2012. The sNDA for the ANCHOR population requires that the cardiovascular outcomes study be “substantially underway,” a milestone that the company projects will occur by the end of 2012. It remains to be seen whether the six-month review cycle currently enjoyed by sNDA files will be lengthened under the new “PDUFA V”  legislation that would take effect October 1, 2012. Therefore, it would be best to model mid-2013 as the earliest timing for additional supplier approvals and late 2013 for the approval of the expanded indication. Finally, management suggested that a clinical trial of a combination (AMR101 plus undisclosed statin) would begin in 2012.

The patient population sizes (and by extension, sales opportunity) that are thrown around by the company and AMRN bulls (tens of millions of patients in the United States alone) need to be considered in the context of how much supply Amarin could actually put on the market. Last fall, management made a comment that the first three API suppliers could generate about 1000 metric tons annually, corresponding to $1.2-1.3 billion in revenue. On the 1q-2012 call this guidance seems to have increased to some extent, as the comment was that the 4 suppliers could quickly ramp to “a thousand or multiple thousand” metric tons (quoted same $1.2-1.3b figure “at today’s pricing”).

Competitive Landscape and Reimbursement:

The first question of the call was related to the recently announced top-line data for a potential competitor product, EPANOVA from Omthera Pharmaceuticals. Management was very dismissive of the data and the competitive threat, emphasizing that AMR101 had equal or superior efficacy for each metric disclosed (triglyceride lowering, synergy with statin, LDL, non-HDL, side effects/dropouts), as well as positive data for other endpoints (ApoB, Lp(a), or other biomarkers) that Omthera did not disclose in their press release. AMRN pointed out that Omthera did not disclose placebo arm results and that “there might have been an issue with how they were measuring that.” We will await presentation of these EPANOVA results at a medical meeting for a more complete comparison.

Several points about competitor LOVAZA from GSK were made in the context of commercializing AMR101. Anecdotal reports have emerged that insurers are requiring patients to demonstrate triglyceride levels >500 mg/dL before reimbursing LOVAZA use. This sounds like a double-edged sword, as it would reduce off-label competition from LOVAZA after the ANCHOR population approval, but would stifle such off-label use of AMR101 in the meantime. The company also said that their data suggest that GSK has maintained direct to consumer advertising, but has backed off promotion by the sales force over the past year or two – “this is a promotionally sensitive market” and may explain lag in LOVAZA prescriptions.

Amarin reiterated that they look at AMR101 as being well differentiated from LOVAZA – in what it does and price, but we are cognizant of the market we are in. They are doing a lot of market research and have had discussions with all of the key managed care players, and are “delighted with what we are seeing so far.” Amarin has reassembled many executives from Reliant Pharma which developed LOVAZA, and is now also working to establish their medical science liason (MSL) group. Two keys to marketing-  1) convert patients from other products and 2) expand the market – MARINE indication currently has only ~15% penetration, ANCHOR population technically not penetrated at all. We have made no definitive decisions around pricing, but want to hit market aggressively and achieve Tier 2 formulary status as quickly as possible.


Amarin has been and will continue to be a volatile stock and potential investors need to either monitor the chatter daily or buy it as long-term hold based on the sheer market potential, high probability of regulatory approval, and takeover speculation. The issuance of the first patent in March 2012 has definitely been viewed by the market as a de-risking event, moving AMRN stock up a couple dollars per share to a $10-12 range. We are positive on the stock longer term and believe the product could likely deliver blockbuster sales of $1-2 billion or more. However, the success is highly contingent on enormous sales and marketing effort and spending, leading us to be uncomfortable with the prospect of Amarin trying to lead commercialization alone. We believe that short term dips due to unfavorable patent news (actual or perceived), a PDUFA delay, or general market weakness may offer an attractive entry point.


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