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Leber’s Congenital Amaurosis Type 10

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ivet
0
lijkt me overzichtelijker een aparte draad te openen voor deze trial;



ProQR Receives Fast Track Designation from the FDA for QR-110 for Leber’s Congenital Amaurosis Type 10

GlobeNewswire•May 31, 2017Comment
Key Updates

ProQR receives Fast Track designation by the U.S. Food and Drug Administration (FDA). Closer interaction with FDA could potentially accelerate the development of QR-110 in patients with Leber’s Congenital Amaurosis Type 10 (LCA 10).
LCA 10 is one of the most prevalent forms of gene-related blindness in children worldwide and currently there are no therapies commercially available or in clinical development.
QR-110 is currently in clinical development with the planned Phase 1/2 open-label trial (PQ-110-001) that will assess the safety, tolerability, pharmacokinetics and efficacy of multiple administrations of QR-110 in one eye of each patient and will include approximately 6 adults and 6 children with LCA 10.
Top-line trial results are expected in 2018.
LEIDEN, the Netherlands, May 31, 2017 (GLOBE NEWSWIRE) -- ProQR Therapeutics N.V. (PRQR) today announced that it received Fast Track designation from the U.S. Food and Drug Administration (FDA) for QR-110, the lead molecule in its ophthalmology pipeline. QR-110 is being developed for the treatment of patients with Leber’s Congenital Amaurosis Type 10 (LCA 10), a rare genetic disease that causes individuals to lose sight, often in the first years of life. QR-110 is a novel investigational RNA oligonucleotide targeting LCA 10 due to the p.Cys998X mutation, which is one of the most prevalent forms of gene-related blindness in children and currently there are no disease modifying therapies commercially available or in clinical development.

Fast Track designation is granted by the FDA to drugs that are under development for serious conditions and have the potential to fulfill an unmet medical need. It was established with the intention to bring promising drugs to patients sooner by facilitating the development with more frequent FDA interactions and expediting the review process.

“QR-110 is a unique and elegant approach to addressing the underlying genetic defect that leads to blindness in individuals with LCA 10 due to the p.Cys998X mutation. We are very pleased with granting of the Fast Track designation by the FDA for this program as it highlights the need for innovative and efficacious medicines for this devastating disease for which there is currently nothing available,” said Noreen R. Henig, Chief Medical Officer of ProQR. “We are also excited to be able to initiate our first trial for QR-110 as a multidose study and for that we will benefit from the Fast Track Designation. We believe development of QR-110 also opens the possibilities for RNA approaches to target other causes of genetic blindness. We are building our pipeline in ophthalmology and will use our rapid development approach to QR-110 as a model for how to bring RNA therapeutics to patients in need.”

About ProQR
ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases such as cystic fibrosis, Leber’s congenital amaurosis Type 10 and dystrophic epidermolysis bullosa. Based on our unique proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind.
*Since 2012*

About QR-110

QR-110 is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of Leber’s congenital amaurosis Type 10 due to the p.Cys998X mutation in the CEP290 gene. The p.Cys998X mutation is a substitution of one nucleotide in the pre-mRNA that leads to aberrant splicing of the mRNA and non-functional CEP290 protein. QR-110 is designed to restore wild-type CEP290 mRNA leading to the production of wild-type CEP290 protein by binding to the mutated location in the pre-mRNA causing normal splicing of the pre-mRNA. QR-110 is intended to be administered through intravitreal injections in the eye and has been granted orphan drug designation in the United States and the European Union.

About Leber’s Congenital Amaurosis Type 10

Leber’s congenital amaurosis is the most common cause of blindness due to genetic disease in children and consists of a group of diseases of which LCA Type 10 (LCA 10) is one of the more severe forms. LCA 10 is caused by mutations in the CEP290 gene of which the p.Cys998X mutation is most common. LCA 10 leads to progressive loss of vision causing most patients to lose their sight in the first few years of life. To date, there are no treatments approved or products in clinical development that treat the underlying cause of the disease. Although prevalence rates vary, we believe approximately 2,000 people in the Western world have LCA 10 because of this mutation.

About the PQ-110-001 Study

PQ-110-001 is an open-label trial that will include approximately 6 children (age 6- 17 years) and 6 adults (= 18 years) that have LCA 10 due to one or two copies of the p.Cys998X mutation. During the trial, patients will receive four intravitreal injections of QR-110 into one eye; one every three months for one year. The QR-110 trial is expected to be conducted in three centers with significant expertise in genetic retinal disease in the US and Europe.
Frenky_Tornado
0
Zeer interessant project! Het gaat om een groep ziektes die vergelijkbaar zijn en dus met eenzelfde strategie bestreden kunnen worden. Daarbij komt dat iedere patient in de trials zijn eigen controle is. Om controle patienten in clinical trials te krijgen is erg lastig en ethisch ook erg moeilijk. De wetenschap eist controles, maar om ernstig zieke mensen met placebo's te behandelen is voor een arts erg moeilijk. Bij deze trial is dat dus geen probleem.

Afwachten hoe het gaat.
Prof. Dollar
0
quote:

Frenky_Tornado schreef op 12 jun 2017 om 09:55:


Zeer interessant project! Het gaat om een groep ziektes die vergelijkbaar zijn en dus met eenzelfde strategie bestreden kunnen worden. Daarbij komt dat iedere patient in de trials zijn eigen controle is. Om controle patienten in clinical trials te krijgen is erg lastig en ethisch ook erg moeilijk. De wetenschap eist controles, maar om ernstig zieke mensen met placebo's te behandelen is voor een arts erg moeilijk. Bij deze trial is dat dus geen probleem.

Afwachten hoe het gaat.

Hi Frenky_Tornado, kun je de onderstreepte zin toelichten?
Frenky_Tornado
0
Hi Prof.,

Jazeker. Het wordt in 1 van de ogen toegediend, het andere oog blijft dus onbehandeld en kan als controle dienen. Op die manier heb je dus een prima controle groep. Je hoeft dus niet een groep mensen te recruteren met de ziekte en die met een placebo te behandelen. Dat is lastig bij zeldzame aandoeningen en degene die de placebo krijgt is uiteraard niet blij. Wel ellende van een behandeling, maar zonder resultaat.

Groet,

Frank

Prof. Dollar
0
Dank! Dat klinkt plausibel. In het draadje Biotechnologie heb ik een vraag staan over de technologie van ProQR: www.iex.nl/Forum/Topic/1339556/10/Bio... Wellicht heb jij daarop een antwoord.
Prof. Dollar
0
Heeft er iemand referenties (wetenschappelijke data, presentaties of eventueel dat van analisten) die specifiek in gaan op het mRNA-platform van PRQR?

Zij-stapje ter voorbeeld: over de 'bouwsteentjes' (vector, promotor, gen en toedieningstechniek) van uniQure (QURE) is tamelijk veel te vinden. Soortgelijk iets zoek ik voor PRQR.
PlayBall10
1
Daniel de Boer, Founder and CEO of ProQR, discusses Leber’s congenital amaurosis (LCA), the most common genetic cause of childhood blindness that affects about 15,000 patients in the Western world. checkrare.com/lebers-congenital-amaur...
Tom3
0
Beetje laat wellicht maar hier is de bevestiging dat in november 2017 de eerste patient behandeld is. Na 6 maanden volgt een interim bericht. Wellicht dat we in september iets kunnen verwachten? Ondertussen is op Facebook een zondvloed aan berichten te zien die tot doel hebben patienten te mobiliseren voor de Luxturna operatie, geen middel wordt daar geschuwd. De luxturna resultaten lijken verder goed te zijn.
www.blindness.org/content/proqr-doses...
www.bceye.com/luxturna-first-gene-the...
Tom3
0
Naast de ontdekking van de Usher syndroom therapie al weer een super interessante ontdekking door het Radboud MC gepubliceerd in november 2017:

www.radboudumc.nl/nieuws/2017/eerste-...
Tom3
0
quote:

Tom3 schreef op 3 jun 2018 om 01:07:


Het niet allemaal zo geweldig zoals het in het in de social media wordt voorgesteld:
www.vox.com/2018/3/22/17147312/luxtur...


Heel belangrijk om te weten dat de Spark Luxturna therapie betrekking heeft op het RPE65 gen. Ik verkeerde in de veronderstelling dat ook zij het gemunt hadden op het cep gen.

Editas heeft zich met haar Crispr/Cas9 methode wel op het cep290 gen gestort:
www.editasmedicine.com/areas-of-resea...
Hunter300
1
Skip to Main Content

Splice-modulating oligonucleotide QR-110 restores CEP290 mRNA and function in human c.2991+1655A>G LCA10 models
Kalyan Dulla*, Monica Aguila*, Amelia Lane, Katarina Jovanovic, David A. Parfitt, Iris Schulkens, Hee Lam Chan, Iris Schmidt, Wouter Beumer, Lars Vorthoren, Rob W.J. Collin, Alejandro Garanto, Lonneke Duijkers, Anna Brugulat-Panes, Ma’ayan Semo, Anthony A. Vugler, Patricia Biasutto, Peter Adamson, Michael E. Cheetham'Correspondence information about the author Michael E. CheethamEmail the author Michael E. CheethamEmail the author Michael E. Cheetham
*Contributed equally to this work.
Published Online: July 23, 2018
Publication stage: In Press Accepted Manuscript
Open Access
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DOI: doi.org/10.1016/j.omtn.2018.07.010
Open access funded by World Health Organization
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Abstract
Leber congenital amaurosis 10 (LCA10) is a severe inherited retinal dystrophy associated with mutations in CEP290. The deep intronic c.2991+1655A>G mutation in CEP290 is the most common mutation in LCA10 individuals and represents an ideal target for oligonucleotide therapeutics. Here, a panel of antisense oligonucleotides was designed to correct the splicing defect associated with the mutation and screened for efficacy and safety. This identified QR-110 as the best performing molecule. QR-110 restored wild-type CEP290 mRNA and protein expression levels in CEP290 c.2991+1655A>G homozygous and compound heterozygous LCA10 primary fibroblasts. Furthermore, in homozygous three-dimensional iPSC-derived retinal organoids QR-110 showed a dose-dependent restoration of mRNA and protein function, as measured by percentage and length of photoreceptor cilia, without off-target effects. Localization studies in wildtype mice and rabbits showed that QR-110 readily reached all retinal layers, with an estimated half-life of 58 days. It was well tolerated following intravitreal injection in monkeys. In conclusion, the pharmacodynamic, pharmacokinetic and safety properties make QR-110 a promising candidate for treating LCA10 and clinical development is currently ongoing.

Declaration: This work was funded by ProQR. KD, IS, HLC, IS, WB, LV, PB and PA are employees of ProQR. MEC has acted as a consultant to ProQR.

Received: February 23, 2018; Accepted: July 18, 2018; Published online: July 23, 2018
© 2018 The Author(s).
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Copyright © 2018 Elsevier Inc. except certain content provided by third parties
Tom3
0
ivet
0
Handel is rustig en de koers wordt gedirigeerd. Zichtbaar is dat kopers (grote koper?) actief zijn (is). Ah einde steeds ff naar beneden voor een beter uitgangspunt voor de volgende handelsdag.
Tom3
0
quote:

Tom3 schreef op 10 jun 2018 om 15:22:


[...]

Heel belangrijk om te weten dat de Spark Luxturna therapie betrekking heeft op het RPE65 gen. Ik verkeerde in de veronderstelling dat ook zij het gemunt hadden op het cep gen.

Editas heeft zich met haar Crispr/Cas9 methode wel op het cep290 gen gestort:
www.editasmedicine.com/areas-of-resea...


Bij Editas/ Allergan zullen ze nu wel wakker zijn geworden na de prima resultaten van ProQR op het Ziekte van Leber front:
www.investopedia.com/news/allergan-ed...
Tom3
0
Twitter berichten zijn in dit geval ook nuttig te lezen:
twitter.com/proqr

#ProQR announces positive interim results from Phase 1/2 clinical trial of #QR110 in #LCA10 patients, and plans to start a Phase 2/3 pivotal trial. #Ophthalmology #RetinalDisease. Read the press release here: bit.ly/2wIhVCI
Tom3
0
Bijgaand een uitvoerig artikel mbt tot de vorderingen van Editas op LCA10 gebied:

www.nature.com/articles/d41587-018-00...

"Editas is facing unexpectedly stiff competition in its lead indication, as Leiden, the Netherlands-based ProQR Therapeutics is gearing up to move an RNA-based antisense oligonucleotide therapy, QR-110, into a pivotal phase 2/3 trial in Leber's congenital amaurosis type 10 next year, after reporting unexpectedly positive data from a phase I/2 trial in September. The therapy elicited clinically meaningful improvements in vision in about 60% of the participants. "Nobody thought that targeting RNA was going to work in that way," says Michel Michaelides, professor of ophthalmology at University College London. What's more, ProQR’s delivery method, intravitreal injection, did not cause problems with inflammation. Subretinal delivery, in contrast, involves retinal detachment, which can lead to retinal tears, macular holes and other complications that may require further surgery. "Detaching the retina is a far more risky thing to do," he says. At the same time, if it works, EDIT-101 may only require a single administration, whereas QR-110 requires ongoing injections."
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