Favourable Lovaza data ups the ante in fish-oil competition

Under pressure from fish-oil competitor AMR101, Lovaza’s backers have come out swinging. Pronova BioPharma and partner Takeda are touting the results of a pivotal phase III Japanese trial as evidence the two omega-3 fatty acid pills are therapeutically equivalent in reducing high triglycerides.

Shares in the Norwegian group have risen steadily following announcement of the trial results, reaching a six month high of NKr10.60 on May 18 as investors have interpreted the Japanese trial as a way of Lovaza improving its chances against Amarin’s upstart. However, to counter one of AMR101/Epadel’s big advantages, Pronova’s partners would need to press regulators for a label change, a challenging process; and as Pronova is fighting threats on multiple fronts, the share bounceback may be premature (Event - Lovaza patent trial crucial to halt Pronova's bad run, March 28, 2011).

Big in Japan

The Japanese registration trial in 611 patients found that a 4g dose of Lovaza, known in Japan as TAK-085, was statistically superior to Epadel at 1.8g, the approved Japanese dosage, in lowering triglycerides 12 weeks after a baseline measurement. Both the 2g Lovaza and 1.8g Epadel significantly lowered triglycerides.

But significantly, the Japanese researchers registered no increase in low-density lipoproteins (LDL), so-called bad cholesterol. Based on clinical trials data, US prescribing information calls for physicians to monitor LDL and this was thought to be a weakness for Lovaza as trials of AMR101 have seen no rise in LDL.

Amarin has long hypothesised that the absence of DHA from AMR101 makes the difference on LDL elevation, and has pitched this as a competitive edge.

“As far as I see it I think they are roughly comparable with regard to side effects and with LDL effects,” says Göran Gannedahl, Pronova’s vice president or medical and regulatory affairs and research & development. “There is a dose-dependent relationship. To me, it’s not a surprise.”

That the 4g dosage is superior to 1.8g is no surprise. The scientific literature has consistently shown a dose-response relationship. A recent article in the American Journal of Clinical Nutrition compared patients with moderately elevated triglycerides compared the effect of a 3.4g dose of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the therapeutic components of Lovaza, to a 1.8g dose. The lower dose did not significantly reduce triglycerides; the higher dose did.

If the emerging evidence that Lovaza does not raise LDLs is consistently borne out, however, it could provide fodder for a label change. From Pronova’s perspective, whether Lovaza receives a label change will rely on its partners, GlaxoSmithKline in the US and Abbott Laboratories in Europe, and will likely require further trials. A GSK spokeswoman would not comment on whether that will happen.

One can see why Pronova is anxious to make that pitch. Lovaza is its only product, and with generic competition in 2015 it is nearing its peak sales - $1.1bn is forecast for next year, declining to $740m in 2016, according to EvaluatePharma consensus data. For Pronova, royalties are estimated to peak at $36m in 2014 before falling back to $23m in 2016.

Big in America

Amarin is expected to file AMR101 for approval later this year and a launch is expected in 2011, with sales forecast to reach $2.26bn in 2016. Those comparatively big forecasts are the result of AMR101’s success in more patients. AMR101 has also tested well not only in severe hypertriglycerideamia patients, defined as triglycerides greater than 500mg per decilitre of blood, in which Lovaza is approved, but also in the wider population with high triglycerides, between 200 and 500mg/dL (Amarin surges as hopes for heart drug soar,April 18, 2011).

As Amarin’s fortunes have risen, Pronova’s have fallen: with the US company’s shares rising sixfold in the last year and the Scandinavian competitor down by 38%.

Lovaza does have one thing on its side: Big pharma marketing partners in GSK and Abbott, who market the pill as Omacor. Amarin has previously made noise about bringing the product to market itself without a big pharma partner or buyer – helped by a $105m share offering earlier this year.

“If it were Amarin by itself, it would be difficult for Amarin to take on GSK. If the drugs were equivalent, it would be a slugfest,” says Duane Nash, an analyst with Wedbush in San Francisco.

However, most have Amarin slated as a takeout target, especially as it has a single product with only one additional phase II hope in the pipeline. Mr Nash notes, however, that the only problem with those expectations of a trade sale is the possibility that Amarin could become overpriced. At present it looks like good value with the net present value of AMR101 at $6.31bn  considerably above Amarin's market capitalisation of $2.32bn.

If Amarin does get a big partner or sells out to a bigger company, Lovaza is going to be on the back foot in the coming marketing battle given the efficacy concerns, which may explain why GSK was willing to settle a patent challenge to Lovaza from Apotex so quickly after its US patent trial started (Pronova's compromise with Apotex a step in the right direction, March 30, 2011).

Settling with the other two parties to that trial would probably allow the British firm to think more clearly about its response to the AMR101 threat should it come as expected at the beginning of next year. A couple more years of steady revenue from the fish-oil pill would be appreciated in the midst of other patent expirys – one-third of GSK’s portfolio faces generic competition in the next three years (Pfizer patent cliff dwarfs peers as loss of Lipitor looms, February 1, 2011) .

However, AMR101’s trial data has been impressive and looks like it will be a tough product to beat, given its wider patient population and the expectation its label will be more favourable in reporting LDL response. Pronova may be swinging, but Amarin may be able to take the punches.

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