Förra veckan kunde Abliva meddela positiva säkerhets- och farmakokinetiska data från sin fas Ia/b-studie med KL1333, samt signaler om effekt i relevanta kliniska effektmått hos patienter med primära mitokondriella sjukdomar. BioStock kontaktade bolagets vd Ellen Donnelly för en kommentar.

Den 16 mars meddelade det svenska bioteknikbolaget Abliva att den kliniska fas Ia/b-studien med KL1333, bolagets läkemedelskandidat för kronisk oral behandling av primära mitokondriella sjukdomar (PMD) har slutförts. Inga allvarliga biverkningar rapporterades och bolaget kommunicerade att studiedata skulle utvärderas under våren och försommaren. Förra veckan offentliggjordes det slutliga resultatet av dataanalysen.

Positiva fas Ia/b resultat

Det primära syftet med den dubbelblindade, randomiserade, placebokontrollerade fas Ia/b-studien var att utvärdera säkerheten och farmakokinetiken för KL1333, både hos friska frivilliga och hos patienter.

Data från studien bekräftar data för ökande engångsdoser från en tidigare fas I-studie och visar för första gången data för multipla ökande doser från friska frivilliga samt upprepad daglig dosering i patienter. Studien inkluderade en analys av kostens inverkan och uppdelad dosering av KL1333 hos friska frivilliga samt en fullständig sammanfattning av farmakokinetiska parametrar hos både friska frivilliga och patienter med primära mitokondriella sjukdomar.

Vd kommenterar

BioStock kontaktade Ablivas vd Ellen Donnelly för en kommentar kring studieresultaten, dess betydelse för den fortsatta utvecklingen samt hennes framtidsvisioner för kandidaten.

Ellen, first of all, congratulations on the study results. The study was conducted in collaboration with neurologists at the University College London and the Welcome Trust Centre for Mitochondrial Research at Newcastle University. What were the research group’s reactions to the study results, given that there are currently no treatments targeting primary mitochondrial diseases?

– We spoke with the investigators this week and they were, of course, very pleased that the study met its primary objectives, to demonstrate safety and characterise the pharmacokinetic profile in primary mitochondrial disease patients. With these results in place, KL1333 can move forward in clinical development towards regulatory approval of an innovative treatment opportunity to patients which currently lack any proven efficacious and disease-specific therapies. The investigators, as well as we, are aware of the limitations to drawing firm conclusion from such a small and short study, but the positive changes seen in disease-relevant outcome measures provide important data for us as we finalize the phase 2/3 study design and are of course encouraging for the overall objectives of the program.

Despite the fact that the study was not primarily designed to evaluate efficacy and the duration of dosing was only 10 days, you could still see promising signs in the cohort that included PMD patients. Can you briefly walk us through the results that you saw in the PMD patients?

– We saw some exciting early signs of efficacy in the PMD patients in our study.  First, the patients treated with KL1333 performed better than placebo patients on two independent fatigue scales and a functional scale called 30 Second Sit-to-Stand.  In addition, the patients with the highest exposure of drug in their blood performed the best on the clinical efficacy measures.  All of this data will be considered as we work to finalize our clinical design for the Phase 2/3 study.

Does the outcome embolden Abliva moving forward, preparing for the phase II/III study?

– Absolutely. This study provided us with important information about safety, efficacy and dosing of KL1333 and this information strengthens our program as we move towards regulatory submission and study start later this year.  A wise mentor of mine once told me that “good drugs declare themselves early” and I hope that this data, in only 8 patients over 10 days of dosing, is our first sign that KL1333 has the characteristics to go all the way to market, into the hands of the patients who desperately need treatments for their disease.

Also, a second pharmacology study evaluating the interaction of KL1333 with seven enzymes (CYPs) that metabolise other drugs has just been completed. What have you learned from this study?

– The study was a comprehensive drug-drug interaction trial including seven of the most important drug metabolising enzymes in the body. Any strong inhibition of induction of these enzymes could pose issues to combining KL1333 with other medicines and limit which patients could be included in upcoming clinical trials. Even though there is no proven ‘disease-specific’ drug approved for multisystemic PMD, these patients are often on multiple symptomatic therapies so strong interactions would have posed a problem. The study results only show a mild inhibition of one of the less common CYPs, CYP1A2, so we are very pleased to see that there were no concerning interactions.

Finally, what remains to be done before you can submit an IND application later this year, and when do you anticipate the phase II/III study can be initiated?

– We have a busy period ahead of us as we work to prepare the package for IND submission.  First, we will use the data from the Phase 1a/1b study (population, dosing, efficacy endpoints, etc) to test our early assumptions on the study design and finalize our clinical protocol.  At the same time, the team is working to finalize the clinical study reports for the Phase 1a/1b study and the DDI study and we are busy running the fatigue validation study.   The team has already started the process of writing the IND, though, so we hope to have everything prepared so that the IND can be submitted as soon as we have all of the supporting data.  We remain on track to have the IND submitted and Phase 2/3 study start in the second half of this year but I will be the first to admit that it will be a busy time and everything needs to proceed as planned for us to achieve these ambitious goals!

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