Back in 2007 a trial subject suffered a dizzy spell during a round of golf, causing Allergy Therapeutics’ Pollinex Quattro clinical programme to be put on US clinical hold. The UK company’s protestations notwithstanding, it took five long years before this hold was lifted, plus another three before trials resumed.
Today’s apparent success in a mid-stage trial in grass allergy will give Allergy’s long-suffering investors hope that its resumed clinical programme could yet deliver. Their attention now turns to the most important 2018 catalyst: readout of a phase III study of another project in birch pollen allergy, expected late this summer.
However, it is impossible to handicap the phase III birch allegy trial based on today’s results. The phase II grass allergy trial was run to select a phase III dose to allow the product to go before US regulators, and in any case Allergy has revealed very little about the data; the phase III birch allergy study is intended to allow the vaccine to gain full approval in Germany.
This is because several of Allergy’s vaccines are marketed in Europe on a named-patient basis, but the German TAV (therapy allergens ordinance) has required products currently sold this way to seek full authorisation with the backing of clinical data.
The birch study completed enrolment in January, randomising over 560 subjects and seeking to demonstrate efficacy versus placebo. The efficacy measure is the total combined symptom medication score of the rhinoconjunctivitis daily symptom score and rhinoconjunctivitis daily medication score, averaged over the peak 2018 birch pollen season.
Though Allergy stock rose 6% today the market should be careful about pricing in success just yet, despite the company’s claims that the phase II grass allergy study had yielded “highly positive” results.
The group has revealed no actual efficacy data, simply providing a p value (<0.0001) that backs a dose-response relationship between four doses tested. Demonstrating dose response was the phase II trial’s primary objective.
The adjuvanted grass allergy vaccine is Allergy’s most important R&D asset, as it represents the group’s attempt to break into the US market. The plan is to use the optimal, currently undisclosed, dose identified in this 447-patient European phase II trial to go into a US phase III study next year.
It is also still unclear whether the planned phase III trial will suffice for approval when paired with a previously completed pivotal study with a lower dose.
The only disclosed hint of phase II efficacy, in terms of change in allergic symptoms after conjunctival provocation, is that the currently marketed product yielded an improvement versus placebo described as significant (p<0.01). This apparently represents the lowest of the four doses, Stifel analysts say, and is the product Allergy sells in Europe on a named-patient basis.
|Grass MATA MPL||PQGrass205||Phase II dose-finding to back US phase III||2017-000333-31|
|Birch MATA MPL||PQBirch301||Phase III to back full German approval||2016-002781-31|
Sharp-eyed followers will also have noticed that Allergy no longer refers to its vaccines pipeline as the Quattro range. This is presumably because the grass vaccine, for instance, now comprises six rather than four subcutaneous injections; however, this is far fewer than with available US “homebrew” products, so Allergy can still boast of having short-course alternatives.
Named-patient EU sales bring in some $90m of revenue a year for Allergy, and this business is profitable. Trying to crack the US market has swallowed up these profits and more, and Stifel bemoans that despite these efforts Allergy’s valuation gives no credit to its pipeline.
Some caution is warranted – there is a risk that Allergy’s products are being overtaken by sublingual treatments developed by Stallergenes and ALK Abello, for instance, though it should be noted that these have so far failed to sell strongly.
The hope for bulls is that eight years in the wilderness has not caused Allergy any terminal damage.