In February data from three patients treated with Reneuron’s
retinitis pigmentosa stem cell candidate raised hopes that the group
might finally have a decent asset. Now, findings in five more patients
have given the company a reality check.
As well as showing less impressive efficacy, two subjects suffered
procedure-related vision loss. Reneuron’s chief executive, Olav Hellebø,
told
Vantage that patients with the disorder, which eventually
causes blindness, would be willing to take this risk. Still, the
company’s shares fell as much as 22% today, and its hopes of finding a
partner look to have taken a blow.
Too good to be true?
One problem, Mr Hellebø argued, was that the previous data had been
seen as “too good to be true”: three patients initially receiving
Reneuron’s human retinal progenitor cells (hRPCs)
showed a mean 23-letter improvement from baseline on the ETDRS chart, a measure of visual acuity, after one to two months’ follow-up.
To put this into context, Sanofi and Regeneron’s age-related macular degeneration blockbuster, Eylea, has
been linked with 8-11-letter improvements.
Those early results with the hRPCs, which came from the phase II portion of a
phase I/II trial, have helped Reneuron’s stock rocket by around 300% over the course of 2019. But the latest data make the project look average.
In total, 10 patients have been treated in the phase II part of the
trial; they received subretinal implantation of hRPCs in one eye, while
the other remained untreated. Today Reneuron reported data on eight of
these patients, the other two having not yet reached 30 days’ follow-up.
Two of the eight experienced procedure-related vision loss. The chief
executive noted that this was down to the surgery rather than the cells
themselves, and that the company hoped to be able to reduce the risk of
this adverse event in future, for example by excluding patients with
very damaged retinas at baseline.
But he argued that, for a serious disease like retinitis pigmentosa, doctors and most patients would accept this risk.
Even if this proves to be the case the latest efficacy data with the
hRPCs look much less impressive than those previously reported. At three
months, the latest timepoint at which data from all eight patients are
available, the mean improvement in visual acuity was 6.1 letters in the
treated eye.
Mr Hellebø blamed the two patients with vision loss, who he said
“lost a lot of letters”, for dragging the result down. Excluding these
two subjects gave a 17.8-letter mean improvement over baseline.
More to lose, less to gain
Still, this result was flattered by the first three patients
enrolled; the second three-patient cohort showed gains of just 5-11
letters at three months, Reneuron said. A breakdown of patients’
individual responses will be included in a presentation October 12 at
the American Academy of Ophthalmology meeting in San Francisco,
according to Mr Hellebø.
He added that a drop-off in efficacy had been expected as the second
group of patients had less severe vision loss at baseline, so had “more
to lose and less to gain”. These patients’ visual acuity had been around
35 letters or more before treatment; below this threshold patients are
classified as legally blind. Meanwhile, the first three subjects had
baseline levels of 9-32 letters.
As well as raising questions about the hRPCs’ safety and efficacy in a
broader patient population, the latest data could give potential
partners pause. Mr Hellebø previously told
Vantage that Reneuron was looking for collaborators outside Europe (
Reneuron eyes a partner with new stem cell data, February 20, 2019).
The group has
already signed up Fosun in China, but it must be hoping for a bigger deal, particularly after
interest from a US speciality pharma group last year.
Longer-term data from the phase I/II trial could give a better idea
of the hRPCs’ true potential, and Reneuron will need to carry out at a
larger phase IIb trial, at least, before being able to seek approval for
the project, according to the Stifel analyst Christian Glennie.
Perhaps any potential partner will want to wait until after these results come in, to see if things become any clearer.
https://www.evaluate.com/vantage/articles/news/trial-results/reneurons-reinvention-falters
