Date: 2022-04-13
Type of information: Results
phase: 2-3
Announcement: results
Company: ProQR Therapeutics (The Netherlands)
Product: sepofarsen (formerly named QR-110)
Action mechanism: antisense drug. Sepofarsen is a RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene.
Disease: CEP290-mediated Leber congenital amaurosis 10 (LCA10)
Therapeutic area: Rare diseases - Genetic diseases - Ophthlalmological diseases
Country: Belgium, Brazil,Canada,France,Germany,Italy, The Netherlands, UK, USA
Trial details: The purpose of this double-masked, randomized, controlled, multiple-dose study is to evaluate the efficacy, safety, tolerability and systemic exposure of sepofarsen (QR-110) administered via intravitreal injection in subjects with Leber's Congenital Amaurosis (LCA) due to the CEP290 p.Cys998X mutation after 24 months of treatment. (NCT03913143)
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Overall, the post-hoc analyses showed that the efficacy signal seen with sepofarsen when comparing active
treatment and sham eyes to their corresponding contralateral eyes across BCVA, FST, and other endpoints,
including PROs, was more consistent with the results seen in earlier findings, where the contralateral eye was
used as the control. Based on these results, ProQR will focus on the following core activities related to
sepofarsen: In Q3, the Company plans to meet with the EMA and FDA to discuss these data from the
Illuminate trial.
Based on the recommendation of the Data Safety and Monitoring Committee (DSMC), the Company currently plans to continue Illuminate, which is a 2 year study, the
Brighten pediatric study, and Insight, until further regulatory guidance, after which next steps will be determined. No further investments are planned
at this time for new trials of sepofarsen or commercial preparations.
Data from theIlluminate trial will be presented at the upcoming Seventh Annual Retinal Cell and Gene Therapy
Innovation Summit, April 29, 2022, and the Association for Research in Vision and Ophthalmology (ARVO)
Annual Meeting, May 1-4, 2022.
Strategy update
The Company also announced the completion of an in-depth strategic review designed to extend the Company’s runway and deliver on its commitment to advance RNA therapies for diseases with high unmet need. Based on the outcomes of this strategic review, the Company will prioritize the following strategic objectives:
- Genetic eye diseases – Explore development path for selected ophthalmology programs based on
comparing active treatment and sham eyes to their corresponding contralateral eyes, subject to regulatory
feedback from the EMA and FDA
- RNA editing technology – Accelerate development of the Axiomer® RNA base-editing technology platform,
including an initial focus on liver, central nervous system (CNS), and the eye.
The Company ended 2021 with €187.5 million of cash and cash equivalents on its balance sheet and expects
these resources, together with anticipated expense reductions resulting from a corporate restructuring and the
strategic update announced today, will fund currently planned operations into 2025, and through several
milestones, including the potential readout of the modified Phase 2/3 Sirius trial of ultevursen.
The Company will implement the following portfolio prioritization and restructuring initiatives with the aim to reduce expenses:
- Focus the ultevursen (QR-421a) program for USH2A-mediated Usher syndrome and retinitis pigmentosa
on a single Phase 2/3 Sirius trial with the potential addition of an interim/futility analysis in 2023. Updates on
planned adjustments to the Sirius trial in light of the findings related to sham control will be provided after
alignment with regulatory authorities;
- Suspend development of QR-1123 for autosomal dominant retinitis pigmentosa and QR-504a for Fuchs endothelial corneal dystrophy;
- Suspend all other IRD-related research activities; and
- Reduce the workforce by approximately 30%, which will include the departure of the Chief Scientific Officer
Naveed Shams, MD, PhD, expected to be effective in Q2.
These efforts are expected to extend ProQR’s cash runway into 2025.
The Company will accelerate the development of its Axiomer® RNA editing platform and pipeline activities and expand into areas beyond the eye, including initially liver and CNS, which have strong alignment with ProQR’s oligonucleotide delivery approaches. In parallel, ProQR will continue to execute on its partnership with Lilly and selectively enter into additional partnerships designed to advance and capture the full potential value of the platform. Since the Company discovered its RNA editing technology in 2014, it has established a leading IP estate in the ADAR editing space, a first industry partnership, and with its broad applicability the platform has significant further potential. ProQR will present further non-clinical data for Axiomer® and announce its internal development targets in H2 2022.
• On February 11, 202, ProQR Therapeutics announced its pivotal Phase 2/3 Illuminate trial of sepofarsen for the treatment of CEP290-mediated Leber congenital amaurosis 10 (LCA10) did not meet its primary endpoint of Best Corrected Visual Acuity (BCVA) at Month 12.
Illuminate, a randomized, sham-controlled trial, enrolled 36 participants aged eight years or older with genetically confirmed LCA10 due to the c.2991+1655A>G (p.Cys998X) mutation in the CEP290 gene, at 14 study sites in 9 countries. Participants were randomized to three equal groups (1:1:1) of the target registration dose sepofarsen (160 ?g/80 ?g loading dose/maintenance doses), a low dose of sepofarsen for masking (80 ?g/40 ?g loading dose/maintenance doses), or sham procedure, with sepofarsen administered via intravitreal injection and the sham procedure mimicking an injection with no drug or injection given. Key findings from the top-line results:
