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.