PharmaShots Interview: ProQR’s Daniel A. de Boer Shares Insight on Sepofarsen for the Treatment of Leber Congenital Amaurosis (LCA10)

In an interview with PharmaShots, Daniel A. de Boer, Founder, and CEO at ProQR shared his views on the P-II/III Illuminate study of sepofarsen for the treatment of leber congenital amaurosis (LCA10)

Shots:

The ongoing P-II/III Illuminate study evaluates sepofarsen in 36 adults and children aged ≥8yrs. with LCA10. The results are expected in late Q1 or early Q2’22
In the P-I/II clinical trial, sepofarsen showed a durable activity, improvement in vision as measured by BCVA. The therapy was well-tolerated with manageable safety findings
The company is also advancing additional RNA therapy i.e., QR-421a in P-II/III trials for other inherited retinal diseases such as USH2A associated retinitis pigmentosa and USH

Tuba: Tell us about Leber congenital amaurosis (LCA10) and its epidemiology?

Daniel: Leber congenital amaurosis (LCA) is the most common genetic cause of childhood blindness and affects about 15,000 people in the Western world. For most people with LCA, there is currently no approved treatment available. It is an inherited retinal disease (IRD) that is passed down through the autosomal recessive pattern of inheritance. It’s a genetic condition resulting in the loss of function of essential proteins. There are over 19 known genes that, when mutated, can cause LCA, one of the most common is the p.Cys998X mutation in the CEP290 gene, causing LCA10. Symptoms usually appear in infancy or childhood and are characterized by severe loss of vision but can also include eye shaking (nystagmus), eye-poking, night blindness, and sensitivity to light.

Tuba: Can we discuss the key features of sepofarsen and how it works?

Daniel: Sepofarsen is an investigational RNA therapy that aims to restore vision in people with LCA10 due to the most common CEP290 gene mutation. The drug works by binding to the mutated RNA and enabling correct splicing restoring the normal RNA sequence. The cells in the retina can then, as a result, produce normal CEP290 protein again and potentially restore the function of the eye.

Sepofarsen is delivered through intravitreal (into the eye) injection, a simple routine procedure under local anesthesia. The drug reaches the entire retina of the patient’s eye. This allows for treatment of the peripheral retina as well as the central retina and potentially allows treatment in the early stages of the disease. In a P-I/II clinical trial of sepofarsen, significant and durable activity with the majority of trial participants having improved vision as measured by best-corrected visual acuity was observed.

Sepofarsen was also observed to be well-tolerated with manageable safety findings.

Tuba: Would you like to share the study design for this P-II/III Trial?

Daniel: Building off of previously reported positive data, the Illuminate study is a pivotal trial currently underway evaluating sepofarsen in LCA10. The trial is on track for top-line data in late Q1 or early Q2 2022. This is an international, double-masked, randomized, sham-controlled clinical trial. In total, the trial has enrolled 36 adults and children (eight years and older). Participants receive intravitreal injections or undergo a sham-procedure where a simulated intravitreal injection is mimicked, and no medicine is administered. Dosing in the first eye takes place at the start of the trial, again at three months, and then every six months. Once participants have completed 12 months in the study, and after a benefit/risk analysis, treatment with sepofarsen of the second eye may begin and those that were in the sham-procedure group may switch to treatment with sepofarsen at this time. The total study participation is 24 months.

Tuba: What are the upcoming milestones for ProQR?

Daniel: In LCA10 patients, in addition to the Illuminate study which is on track for top-line data in late Q1 or early Q2 2022, enrollment is ongoing in the P-II/III Brighten trial which is evaluating the safety and tolerability of sepofarsen in patients under 8 years of age.

ProQR is also advancing additional investigational RNA therapies, such as QR-421a, for other inherited retinal diseases such as USH2A associated retinitis pigmentosa and Usher syndrome, the leading cause of combined deafness and blindness. In this indication, ProQR plans to advance QR-421a into two pivotal P-II/III trials; Sirius in advanced patients, and Celeste in early-moderate patients, by year-end, pending finalization of the study designs with regulatory authorities. Each trial could potentially serve as the sole registration trial.

Tuba: Put a glimpse at ProQR’s recent deal with Eli Lilly.

Daniel: In September 2021, ProQR announced a global licensing and research collaboration of its proprietary Axiomer® RNA editing platform technology with Eli Lilly for $50M, with eligibility to receive an additional

$1.25B in funding. The Axiomer® platform has the potential to reverse the underlying cause of currently untreatable diseases by harnessing the power of the body’s own ADAR RNA editing system to reverse more than 20,000 G to A mutations that are known to cause human disease.

With this partnership, there is potential to expand beyond ProQR’s current areas of focus, genetic eye diseases, into areas that would potentially benefit patients with metabolic and nervous system disorders as well.

Tuba: Do you think that it (the Eli Lilly deal) will boost ProQR’s economy?

Daniel: Yes, this deal has strengthened ProQR’s financial position and validates the potential of the Axiomer technology as an exciting emerging approach to unlocking new treatments for genetic diseases.

Tuba: Can we take a look at ProQR’S pipeline in the ophthalmology space?

Daniel: ProQR has an extensive development pipeline of RNA therapies that use antisense oligonucleotides which are specifically designed to correct the underlying cause of the disease in a person’s RNA and potentially stop disease progression or even reverse symptoms.

ProQR’s pipeline is focused on genetic eye diseases for which there is currently no treatment available. ProQR's most advanced pipeline programs include investigational drugs in CEP290-associated LCA, USH2A-associated Usher syndrome and retinitis pigmentosa, RHO-associated retinitis pigmentosa, and Fuchs endothelial corneal dystrophy. Additionally, ProQR has numerous programs in the discovery stage targeting other mutations causing genetic eye diseases, including Stargardt disease.

Source: Matt Weed

About Author: Daniel A. de Boer is the Founder and CEO of ProQR. Daniel is a serial entrepreneur and passionate advocate for rare disease patients. In 2019 Daniel was selected for the Young Global Leader program at the World Economic Forum.