DBV Technologies still hopes for approval of its peanut allergy patch despite the intriguing disappointment of the phase III Pepites trial – which technically was not a failure. But investors seem unconvinced, wiping 50% off the French company’s value today.
The main beneficiary was Aimmune, up 45% in postmarket trading on Friday, when the data were announced. Aimmune is due to report pivotal data with its own peanut allergy project next year, so it has the chance to steal a march on its rival (see table below).
DBV is convinced that all is not lost. On the one hand the company can argue that Pepites was a success: significantly more Viaskin Peanut-treated patients were classified as responders than those receiving placebo: 35.3% versus 13.6%, with a p value of p=0.00001.
However, this was not enough to meet the primary endpoint agreed with the FDA. The statistical analysis plan for Pepites called for the lower bound of the confidence interval (CI) to be no lower than 15%, and it actually came in at just 12.4%.
During a call to discuss the data, DBV executives described the 15% target as “a high bar”, and blamed a greater than expected placebo response, which was twice that seen at phase IIb, they said. The company had expected a placebo response rate of around 10%.
However, they also conceded that they had hoped for a better response in the treatment arm, with the goal being a 30 percentage point difference between the active and placebo groups. Indeed, analysts had previously set a target of a 45-55% response with Viaskin Peanut, versus 10% in the placebo group (Event – DBV hopes for a smooth ride with peanut data, September 14, 2017).
One problem might have been enrolling patients with a wide range of allergy severity at baseline, which led to two different definitions of response, as assessed by a food challenge.
Specifically, in those with an initial eliciting dose of over 10mg of peanut protein, the eliciting dose at the end of treatment needed to be 1,000mg or greater for the patient to be classed as a responder. In patients with an initial eliciting dose of 10mg or less, the eliciting dose had to reach 300mg or more post-treatment.
The DBV execs would not give details of how the two groups compared in terms of response, but conceded that a difference in baseline sensitivity to peanuts might explain the disappointing results in Pepites compared with the phase II Vipes study.
In contrast, the pivotal Palisade trial of Aimmune’s AR101, an oral project rather than a patch, has enrolled patients with an initial eliciting dose of 100mg or lower; they are classed as responders if they can tolerate 600mg or more at the end of the study.
The more uniform entry criteria and definition of response could give AR101 a better chance of success, some investors believe. Palisade has a primary completion date of November 2017, and data should be available in Q1 2018, according to the company (Interview – DBV and Aimmune head for peanut showdown, March 8, 2017).
Do you Realise?
DBV also has a readout due next month from the real-world Realise safety study, which does not include a food challenge, so is unlikely to shed light on the Pepites result.
Ultimately the company plans to press on with Viaskin Peanut. DBV has already been in touch with the FDA, which executives described as very responsive, adding that the agency had asked the group to continue with its BLA.
“We definitely believe we’re seeing a treatment effect,” said Susanna Mesa, DBV’s senior vice-president of strategy. She added that she believes that the FDA will take the entirety of the data into consideration.
As for the possibility of having to perform another trial, Ms Mesa said that the company would be amenable, “but we don’t think that will be the pathway”.
She highlighted an unmet need in peanut allergy, which could work in Viaskin Peanut’s favour – the project has US breakthrough and fast-track designations. But, if AR101 produces more convincing data, DBV could have a hard time persuading the agency to give its candidate the go-ahead.
|DBV and Aimmune face off|
|Project||Company||2022e sales ($m)||Trial||Data due|
|Viaskin Peanut||DBV Technologies||835||Pepites: NCT02636699||Reported|
|Realise: NCT02916446||Nov 2017|
|People (Pepites follow-up): NCT03013517||Feb 2020|
|Epitope (ages 1-3): NCT03211247||May 2020|
|AR101||Aimmune||1,020||Palisade: NCT02635776||Nov 2017|
|Ramses: NCT03126227||Aug 2018|
|Artemis: NCT03201003||Dec 2018|
|Arc004: NCT02993107||Apr 2020|
|Arc008: NCT03292484||Dec 2020|
This story has been updated to reflect the fact that the AR101 Palisade data are due in Q1 2018, and to clarify the elicting dose and response criteria of the trial.