However, I think you’ll find the explanation below is likely the main reason and certainly a reason previously mentioned by the Company
Small patient populations. Geographic dispersion. Competing studies. Sound familiar? If you’re a sponsor of a rare disease study, you know all too well the challenges that come with recruiting patients. These challenges lead to immense pressure to design and implement studies that limit the burden of participation, while keeping patients engaged and generating high-quality data that can support regulatory approval. While randomized, double-blind, placebo-controlled studies are considered the gold standard of clinical research, it may be difficult to recruit patients with rare diseases into such trials.
More than 90% of rare diseases have no approved therapy. Even when clinical trials are their only opportunity to receive any form of therapy, patients—and their caregivers and clinicians—may be reluctant to participate in studies with a placebo arm due to the risk of non-treatment.
I’d also point out that the recently completed Phase 2 trials in Angelman syndrome run by both Ultragenyx and Ionis also used an open-label rather than placebo-controlled design. And the Phase 2 Angelman syndrome trial commenced by Roche last year and still running, is open-label too.
Ultragenyx has announced details of its Phase 3 trial design and it will be placebo-controlled, with the carrot that all Phase 2 and 3 participants are eligible for treatment in the following open-label extension study.
Finally, just to provide further thought
Both trofinetide in Rett Phase 2 trials were considerably larger than the NNZ-2591 Phase 2 studies. As well as assessing safety and efficacy, optimal dosage still had to be established.
Of the 56 patients who commenced the first, adult trial, only 29 patients were in the highest dose 70mg/kg BID vs. placebo group and that was for just 4 weeks.
Of the 82 patients who commenced the second, paediatric trial, 27 patients were in the highest dose 200mg/kg group BID (the dosage subsequently used, with adjustment, in the pivotal trial) and 24 patients were allocated to placebo. Changes were measured over 6 weeks at full dose and there was no titrating up period.
Hence, of the 138 patients who participated in the placebo-controlled Phase 2 trials of trofinetide in Rett syndrome, just 27 were treated with the dose of trofinetide used in the subsequent Phase 3 trial (200mg/kg BID).
For the NNZ-2591 Phase 2 trials, dosage had already been worked out, so while there were considerably fewer patients, all were treated with the dosage that is intended for use in the pivotal trial. Changes were measured after 13 weeks of treatment, which included 6 weeks of up titration (possibly a lesson learnt from DayBue). Of the ~50 children who participated in the three Phase 2 trials of NNZ-2591, all were treated with the dosage intended for use in pivotal trials (12mg/kg BID).
NEU Price at posting:
$15.76 Sentiment: Hold Disclosure: Held
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