Hypoglycemia ‘Epipen’ clears Phase III, hurtles toward FDA decision

Zealand Pharma is one step closer to delivering a fast-acting injectable for diabetes patients as their HypoPal rescue pen has cleared every primary and secondary endpoint in a Phase III trial on childhood hypoglycemia, confirming results already shown in adults and advancing the drug toward an early-2020 application for FDA approval. The injection, however, was not more effective than rival GlucaGen – and it did make a far higher percentage of teenagers throw up.

The Copenhagen-based company took 42 subjects between ages 6 and 17 and split them into a placebo group, a GlucaGen group and a HypoPal group. Researchers then induced hypoglycemia and tracked for how long it took each group’s blood sugar to recover (first increase in plasma glucose of >/=20 mg/dL) after the drug or placebo was administered.

The 21 HypoPal subjects recovered in 10 minutes, three times as fast as the half-hour it took the placebo group. These results were almost identical to the results from a Phase III trial on adults unveiled in May.
But unlike that trial, this study also contained a group of 10 subjects administered GlucaGen, the longstanding injectable on the market. The GlucaGen patients recovered in the same amount of time as the HypoPal patients. These results mirrored the data from Zealand’s first PhIII trial on adults, from 2018, where HypoPal was only two minutes faster than GlucaGen.

But in this study, the adolescent HypoPal patients also saw far more adverse effects than the GlucaGen patients, although the small sample size – there were only 10 GlucaGen patients – may throw off the percentages. Nearly all (92%) of subjects 12-17 were nauseous after taking HypoPal, compared to 17% of those who took GlucaGen, with two-thirds of that HypoPal age group vomiting. None of the teenage GlucaGen patients threw up.

HypoPal compared well on side effects, though, when it came to children ages 6 to 11, producing the same rate of vomiting and half the rate of nausea.

Zealand has accelerated the buildup of their US operations in anticipation of HypoPal’s launch and begun recruiting key executives to aid the expansion, most notably bringing in former Alnylam executive Emmanuel Dulac as CEO.

Like GlucaGen, HypoPal (dasiglucagon) is made from an analog of the human hormone glucagon. In addition to hypoglycemia, Zealand is investigating using dasiglucagon for hyperinsulinism and for use in artificial pancreas pumps.

Last year, R&D group Novo Nordisk gained rights to glucose-binding molecules from the British biotech Ziylo to look at treatments of hypoglycemia. The deal was worth up to $800 million.

Hypoglycemia ‘Epipen’ clears Phase III, hurtles toward FDA decision