Research note


Orphazyme: Competitor fails in NPC

Mallinckrodt has announced that their VTS-270 project, a competitor to Orphazyme's arimoclomol for the treatment of NPC, failed to show statistically significant efficacy in their Phase II/III trial. No details has been released around the data.

Mallinckrodt's project, VTS-270, is a mixture of 2-hydroxypropyl-ß-cyclodextrins (HPßCD) that is only being studied in NPC. It functions as a cholesterol-binding molecule that removes cholesterol from the lysosomes, which is believed to help in treating patients with NPC. In order to cross the blood-brain barrier, the drug is infused intrathecally (into the spinal canal) either directly (under anesthesia) or through an access port. 

VTS-270 has showed promising early-stage data, albeit in an open-label setting in only 14 patients. The Phase II/III trial included 51 patients between the age of 4 and early 20s. Patients were randomized 2:1 and followed for 52 weeks. Mallinckrodt has repeatedly stated that the analysis of the data is complicated and that they are working with the FDA to find a way forward. While no detailed data has been presented, Mallinckrodt reported during their Q3 earnings call that VTS-270 failed to show statistically significant efficacy. They further stated that neither the placebo nor the actively treated patients progressed according to the hypothesis. 

Mallinckrodt's plan is now to follow through on the open-label part of the trial and to analyze the data in more detail. Discussions with the FDA will be ongoing, and updates could come within the next few months. 

Without any details presented it is not possible to understand how this pairs with Orphazyme's NPC study, where results were presented in late September (note). We note that arimoclomol did not show statistically significant data in the full patient set, but statistically significant efficacy in the primary endpoint for patients above the age of four (same patient group as Mallinckrodt). On the co-primary endpoint, global impression of change (CGI-I), arimoclomol did not show efficacy and patients did not progress as expected. 

For the near future we expect further data around both projects. As mentioned, it is too early to have any certainty regarding the therapies potential in NPC. It is also not clear how the FDA choose to approach the data. Given the seeming hardship of interpreting the data, we expect the uncertainty to remain until more detailed data is available or communication from meetings with regulatory agencies is available. Hence, our initial take is that the news is neither a direct positive nor negative for Orphazyme, but instead we acknowledge the uncertainty regarding the applicability of the endpoints and the FDA's interpretation of the trials and results. Orphazyme will present detailed data, for example around biomarkers and other important disease markers, during Q4-18 or Q1-19.

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