After the alarming widespread losses in biopharma on Christmas Eve it appears that investors were hungry for some good news. What else could explain the tripling in value of NeuroDerm – shares closed up 194% yesterday – on some rather vague results from a phase IIa Parkinson’s trial in just 16 patients?
The trial of ND0612H and ND0612L, high and low doses of the same levodopa/carbidopa therapy, was conducted in Israel. It had to be: the study was initially planned for both Israel and the US, but in June the FDA put it on clinical hold. Analysts are talking of NeuroDerm’s projects as a potential new standard of care for severe disease, but a lot must happen before this prediction can come true.
ND0612 is a liquid formulation of levodopa and carbidopa delivered continuously via a device similar to an insulin pump that the patient wears on a belt. Oral levodopa has a short half-life, leading companies to try different routes of administration; at least NeuroDerm’s pump seems less unusual than AbbVie’s Duopa intestinal gel (Upcoming events: FDA decisions for AbbVie’s Duopa and Merck’s V503, December 5, 2014).
In the phase IIa trial, ND0612-003, the low-dose form was administered for eight hours per day for three consecutive days to nine patients, and the high-dose version to a further seven. The patients had advanced Parkinson’s with motor fluctuations and had been chronically treated with oral levodopa/carbidopa.
A topline, intent-to-treat analysis showed that the maximum daytime levodopa concentrations seen with ND0612H were 1,333ng/ml and 1,436ng/ml with different carbidopa concentrations in the formulation; NeuroDerm did not say what these concentrations were. Addition of oral entacapone raised the maximum levodopa level to 1,807ng/ml.
The low-dose form, ND0612L, achieved maximum daytime concentrations of 528ng/ml and 477ng/ml, again with the undefined different carbidopa levels, and 596ng/ml with adjunct entacapone.
The per-protocol analysis, omitting three datasets from two patients because of concomitant use of oral levodopa, yielded similar levodopa plasma values.
As might be hoped, the constant administration caused a reduction in fluctuations in levodopa plasma levels compared with oral levodopa/carbidopa dosing. The company said both doses raised plasma levodopa to “clinically significant” levels.
As nebulous as these data are analysts from Roth Capital Partners were not discouraged from stating that the project could become the new standard of care for severe Parkinson’s. Scott Henry wrote in a note that obtaining the levodopa levels seen with ND0612H would have previously required surgical intervention, though he amitted to being “a bit surprised” by the magnitude of the stock price jump.
And it does seem quite a leap considering the project is not going anywhere fast in the US. Six months ago the FDA placed a clinical hold on the ‘003 trial until NeuroDerm completed an extractables and leachables study as well as providing more information on the delivery pump. The pump is approved in the EU, but as US device approvals often lag Europe by some years it is possible that it is not FDA-cleared.
NeuroDerm believes it can get the clinical hold lifted in the next few months, and will begin US trials in the second half of 2015. It certainly has the wherewithal to fund ND0612’s development, including the additional FDA-mandated trials, after its shares’ astonishing performance. The company only floated in November.
But ill-defined results in just 16 patients is not much to go on, even in a disorder as difficult to treat as Parkinson’s. NeuroDerm must hope that its prosperity continues into 2015.