Hopes are rising that the world might brighten for another group of patients with a very rare form of inherited blindness, after Spark’s success with Luxturna. Encouraging data on Proqr’s RNA therapy in patients with Leber’s congenital amaurosis emerged yesterday, and the company pledged to get the treatment into a pivotal study in the coming months.
The big red flag here is that the results are from only 10 patients, though this did not stop investors adding more than $300m to the Dutch company’s valuation yesterday. A $75m equity raise followed swiftly and dented enthusiasm somewhat, but it is worth remembering that Proqr has the only clinical-stage project targeting these patients, who carry a very specific gene mutation.
Leber’s congenital amaurosis (LCA) is the most common form of inherited sight loss in children. There are several different subtypes, with various genes responsible for causing a range of sight problems.
The target of Proqr’s therapy is a gene called CEP290, which causes LCA type 10. Another common gene mutation is RPE65, which causes LCA type 2, and can be treated with Spark’s Luxturna. RPE65 is also implicated in related conditions like retinitis pigmentosa, and Luxturna is approved broadly in RPE65 mutation-associated retinal dystrophy.
LCA type 10 is very severe and typically will cause blindness by the age of six. LCA type 2, meanwhile, tends to cause light sensitivity disease, so comparing the two treatments is not strictly relevant.
Also, unlike Luxturna, a once-and-done gene therapy, Proqr’s QR-110 is an RNA therapy, which will probably have to be injected into patients’ eyes four times a year. QR-110 is an oligonucleotide that binds to the mutated section of RNA, allowing the normal from of the CEP290 protein to be produced.
Line in the sand
To an extent Luxturna drew a line in the sand for the approval of such genetic therapies, in terms of acceptable levels of safety and efficacy. And in its presentation yesterday Proqr chose to hold QR-110 up against the Spark product, and claimed to have found comparable levels of improvements, albeit from different baselines.
|Treating LCA - QR-110 and Luxturna|
|QR-110 Phase 1/2 in LCA10||Luxturna Phase 3 in LCA2|
|Visual Acuity||-0.67 LogMAR (p=0.01);
62.5% improved >0.3 LogMAR
|-0.16 LogMAR (p=0.17)|
|Mobility course||Mean of 2.6 levels improvement.
57% of patients improved >2 levels
|1.6 light levels improvement compared to placebo|
|Source: Company presentation.|
A clinically meaningful response was seen in six of 10 patients at the interim stage, on visual acuity scores and on a mobility test, Proqr said. And, while PQ-110-001 was only a proof-of-concept study, the interim results were encouraging enough to halt enrolment and start talks with regulators about a pivotal trial.
The company had intended on testing three doses of QR-110, but in the end the highest dose was never given. Questions about a lack of dose response were brushed off by the company, and a spokesperson told Vantage that the result was what it had expected to see, based on preclinical research.
The 11 patients enrolled in PQ-110-001 will be followed for 12 months, though readout will not emerge until the end of 2019. By that time, if all goes well, Proqr will have started its pivotal phase II/III trial, meaning that investors have little more than these initial data to go on for now.
With nothing else in the clinic targeting CEP290 mutations, this haste is certainly not required commercially. However, with regulators amenable and investors readily funding such ambitious plans, there is very little holding QR-110 back. A tangible safety concern from the field could change all this, of course, but for now it’s green lights all the way for companies like Proqr.