Now that Amarin’s Vascepa is virtually assured of a broader US label than it has enjoyed so far, others are hoping to jump on the fish oil bandwagon. The next important clinical datapoint will come from a small Canadian biotech called Acasti, whose rival project CaPre should yield phase III results next month.
This is not to say that Amarin could suddenly have a major competitor, as Acasti’s trials are in the narrow severe hypertriglyceridaemia setting. But Acasti is capitalised at just $175m, so the investment case at this point might be that positive data attract a player keen to get a foothold in this space.
A deal of this magnitude could represent a relatively small outlay, the bulls might think, and a cash-rich partner could then finance the large, cardiovascular outcomes study necessary to broaden CaPre’s potential label and bring it into line with what Vascepa looks set shortly to enjoy.
That said, there are other considerations. For one thing, next year will see the readout of a large cardiovascular outcomes trial of Astrazeneca’s Epanova that could have huge ramifications for all players. Moreover, Vascepa is set to lose patent protection in 2029 – around the time a potential cardiovascular outcomes trial for CaPre would be expected to complete.
|% of mkt cap||380%|
|Event||Phase III data from Trilogy-1 & 2 studies|
|Due||Dec 2019 & Jan 2020 respectively|
It is important to remember what each of these competing omega-3 projects comprises. Vascepa is a pure form of eicosapentaenoic acid (EPA), while most competitors contain a mixture of EPA and docosahexanoic acid (DHA). All such products lower triglycerides, but Amarin argues that those containing DHA can raise LDL, or “bad” cholesterol, something that EPA does not do.
Acasti has a different argument. CaPre is also an EPA/DHA mixture, but it is sourced from krill oil, which the group claims yields phospholipids that transport these omega-3 fatty acids more efficiently than fish oil-derived EPA/DHA, which must undergo additional digestion.
The Canadian company is running two near-identical pivotal trials, Trilogy-1 and 2. Each screened 615 subjects to obtain 245 expected to have fasting triglycerides in the severe range, namely 500-1,500mg/dl, and aims to show that CaPre can reducing these from baseline over 12 weeks with statistical significance versus placebo.
Bulls will want Acasti to repeat the success CaPre scored five years ago in Trifecta, a phase II, placebo-controlled study.
With data cleanup 90% complete Trilogy-1 is expected to read out in December; Trilogy-2 will be toplined in January, with full data, including results for key secondary and exploratory endpoints like non-HDL-C, LDL-C, VLDL, HDL-C and HbA1c, expected at scientific meetings starting next year.
|Selected omega-3 products|
|Product||Company||Components||Approved setting||Future setting?||2024e sales|
|Vascepa||Amarin||Icosapent ethyl (pure form of EPA)||TG ≥500mg/dl||TG 159-499mg/dl (Reduce-It trial, positive adcom vote)||$2.2bn|
|Epanova||Astrazeneca (ex Omthera)||Omega-3-carboxylic acids comprising EPA (550mg) & DHA (200mg)||TG ≥500mg/dl||TG 180-500mg/dl (Strength trial, reads out 2020)||$176m|
BASF (ex Pronova)
Glaxosmithkline (US, ex Reliant)
|Omega-3-acid ethyl esters comprising EPA (465mg) & DHA (375mg)||TG ≥500mg/dl||TG ≥150mg/dl (Ocean-3 (Japan) trial, reads out 2020)||$293m|
|Omtryg||Trygg Pharma (status unclear)||Omega-3-acid ethyl esters comprising EPA (465mg) & DHA (375mg)||TG ≥500mg/dl||None||None|
|CaPre||Acasti||Omega-3 fatty acids comprising EPA & DHA (krill oil derived)||None||TG 500-1,500mg/dl||$554m|
|MAT9001||Matinas||DPA & and other omega-3 fatty acids||None||TG ≥500mg/dl (bridging study for 505(b)(2) approval)
TG 150-499mg/dl (Enhance-It trial, crossover vs Vascepa)
|Source: clinicaltrials.gov & EvaluatePharma. EPA=eicosapentaenoic acid. DHA=docosahexanoic acid. DPA=docosapentaenoic acid.|
Amarin is the only omega-3 player to show a cardiovascular benefit, but it is also the only company to have completed such a study, and it expects to reap the rewards (Amarin enters the home stretch, November 15, 2019). The debate around each product’s components will not be settled until additional cardiovascular outcomes studies, such as Epanova’s Strength trial, read out.
And much earlier in development Matinas Bio is developing MAT9001, a formulation of DPA (docosapentaenoic acid), which Matinas describes as a potent but less prevalent omega-3 fatty acid. Some years ago a small, open-label, head-to-head trial suggested superiority versus Vascepa on some lipid changes, but the phase II Enhance-It study, also versus the Amarin drug, will not start until next year.
While the broad setting remains too rich for small biotechs to compete in, shifts in the severe hypertriglyceridaemia landscape could provide impetus for further deal making.