When last year DBV Technologies released limited topline data from a phase II study of its lead asset, Viaskin Peanut, it was enough to allow the French company to sell $133m of stock and complete a secondary offering on Nasdaq. Naturally the sellside was ecstatic.
But how much of the enthusiasm was simply down to the biotech bull market? On February 24 the company will face its moment of truth as the full dataset is revealed at the American Academy of Allergy, Asthma and Immunology meeting; smart investors will be awaiting the answers to five key questions.
The phase II Vipes trial had enrolled 221 patients with documented peanut allergies, subjecting them to two peanut protein challenges – one at start and the second after 12 months of daily application of Viaskin Peanut patches.
The trial was deemed a success when DBV said 50% of patients given the 250µg dose responded (increasing their tolerance to the challenge according to prespecified criteria) versus 25% of placebo recipients (p=0.0108; DBV hopes US investors will go nuts for $96m fund raising, September 23, 2014).
However, 250µg was only the highest dose of Viaskin Peanut, and the data excluded 109 remaining patients given 50µg and 100µg. Moreover, the result was driven by the response in 28 children on this highest dose (p=0.008), while 18 adolescents had a non-significant increased response; data on 25 high-dose adults were also not disclosed.
The first thing investors should thus look for is the responses for the remaining doses and remaining patients. There is obvious logic backing maximal activity in the maximal dose, but this needs to be supported by a dose-response effect.
DBV must also explain the relatively high response in placebo recipients, and confirm Viaskin Peanut’s benign safety profile, ruling out serious immune reactions or anaphylaxis. The fourth question leads directly on from the last two: if 250µg works well and there are no safety concerns, why not go back to the drawing board and test even higher doses of Viaskin Peanut?
Finally, DBV needs to explain the lack of activity in older patients, and make the case as to why the paediatric market is the one that counts.
Beyond these specifics there are broader considerations too, such as that of practical applicability. Tolerising patients to the equivalent of four peanuts, as Vipes had tried to do, is not carte blanche for sufferers to eat peanuts at will; rather it suggests a prophylactic for severely allergic children, whose parents are concerned about accidental exposure to even a trace dose.
However, Vipes was not designed to test this, specifically excluding patients with a history of severe anaphylaxis. Then there is the cost and compliance problem of daily patch application, and the fact DBV has not specified whether the impressive p values it cites for the subgroups have been adjusted for multiplicity.
And how relevant is the primary endpoint in Vipes? Analysts have cited key opinion leader support for this definition of increased tolerance to challenge, but whether this is clinically meaningful for protecting against accidental ingestion is uncharted territory.
Despite the questions analysts by and large appear satisfied that Vipes proves the utility not only of Viaskin Peanut but also of DBV’s technology, and numerous sellside notes issued in the wake of the Nasdaq listing forecast peak sales of over $1bn. The company's market value has doubled in the last six months, to €771m ($879m).
For now, investors who pumped €93.7m net into DBV last year seem convinced. Nevertheless, it could be argued that the smart money has already been made, with certain venture capitalists selling €14.8m of stock into DBV’s 2013 financing, and some €11m of the latest raise also being made up of selling shareholders.
While these moves are understandable – it makes little sense to sit on an investment indefinitely – they are not exactly bullish signals. Moreover, much of this existing stock was picked up by biotech-hungry US retail investors. Whether it was worth it should become clearer next week.
|Vipes||221 pts (113 children, 108 adults/adolescents), given 250µg, 100µg, 50µg Viaskin Peanut or placebo||NCT01675882|