Upcoming events – FDA decision for Progenics and Allergy comes out of hiding

Progenics hopes to secure US approval for Azedra, while Allergy Therapeutics awaits phase III data with its birch vaccine.

Welcome to your weekly digest of approaching regulatory and clinical readouts. Progenics hopes to secure US approval for Azedra, its radiotherapy for rare neuroendocrine tumours, and with the pivotal phase II study having met its FDA-agreed primary endpoint the group is confident.

Meanhile, the UK’s Allergy Therapeutics expects a phase III trial of its short-course allergy vaccine Birch MATA MPL, geared towards German approval, to read out this quarter. After spending years in obscurity Allergy hopes to have something to celebrate at last.

12 out of 68

Progenics’ Azedra is a radiotherapy for tumours including recurrent or unresectable pheochromocytoma and paraganglioma. A PDUFA decision is expected by July 30; originally the date was set for April but was extended owing to a request for more CMC information, causing Progenics’ stock to fall nearly 10%. Still, its shares are up 38% so far this year.

Azedra selectively targets the norepinephrine transporter, which is highly expressed on the tumour cell surface. The product is a high specific activity form of iobenguane I 131, a molecule labelled with a cytotoxic radioisotope of iodine.

Pheochromocytomas and paragangliomas frequently secrete high levels of hormones that can lead to cardiovascular complications, and Progenics says these lead to death in 30% of malignant cases.

The phase II trial, in which 18 patients were given a single Azedra dose and 50 patients two doses, met the primary endpoint, showing 17 patients – 16 of whom had received the double dose and one the single – experienced a 50% or greater reduction in all hypertensive medications for at least six months.

Under the study protocol the primary endpoint was said to be achieved if the lower limit of the two-sided 95% confidence interval was above 10%; in the event it was 16.15%. In other words the study needed just 12 of the 68 patients to halve their medication use in order to be considered a success. 

Encouraging response data, part of the secondary measures, were released at this year’s Asco meeting. Among the patients given a single Azedra dose median overall survival was 18 months, while in the 50 treated with two doses this was 44 months. 12-month survival was 91% overall.

Patients will be followed for another four years, with survival being assessed at the five year point. Progenics notes that the current five-year survival of patients with malignant pheochromocytoma or paraganglioma is around 12%.

Trial ID NCT00874614

Allergy seeks the limelight

After emerging from its 11-year spell in the doldrums, occasioned by a US clinical hold, Allergy Therapeutics now turns to its most important 2018 catalyst: readout of a phase III study of Birch MATA MPL, a short-course birch pollen allergy vaccine, expected this quarter.

The result of this trial is hard to handicap. Allergy had a recent mid-stage success with a grass allergy asset – which it followed with a £10.6m ($13.8m) raise – but realistically there is no read-across (After 11 long years Allergy sees a glimmer of hope, May 21, 2018).

An earlier phase II birch pollen study in 371 subjects did read out positively, but that used a different endpoint – total symptom score after conjunctival provocation – and the older version of this asset, branded Pollinex Quattro.

Birch MATA MPL comprises six subcutaneous injections, and its phase III study, in 562 subjects, has as its primary endpoint total combined symptom medication score of the rhinoconjunctivitis daily symptom and daily medication scores, averaged over the peak birch pollen season. The trial is intended to support full approval in Germany.

Bulls will argue that there is similarity between the phase II and III efficacy measures, and that last year’s birch pollen season was especially strong in Europe. Indeed, if it is assumed that the right patients have been enrolled and that the vaccine has been correctly administered, it should not be hard for Allergy to show efficacy.

But risks include accidental inclusion of subjects with other allergies, and the fact that an effect versus placebo – the trial’s comparator – might not translate into a real-world clinical benefit when patients can take OTC allergy pills. Ultimately Birch MATA MPL’s future could be determined by doctors and payers.

Project  Study  Detail  EudraCT ID 
Birch MATA MPL  PQBirch301  Phase III to back full German approval  2016-002781-31

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