ProQR Therapeutics, a company dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases, announced results from a planned interim analysis of its Phase 1/2 trial of QR-110 in patients with Leber’s congenital amaurosis 10 (LCA10) due to the p.Cys998X mutation in the CEP290 gene. LCA10 typically leads to childhood blindness and has no available treatment options. In the trial, QR-110 demonstrated rapid and sustained improvement in vision in patients with LCA10, as measured by visual acuity and the mobility course performance, as well as being well-tolerated with no serious adverse events recorded. Results from this interim analysis were presented earlier today at the Retinal Degeneration 2018 meeting in Killarney, Ireland, by principal investigator Artur Cideciyan, Ph.D., research professor of ophthalmology at the Scheie Eye Institute, University of Pennsylvania.
“The results of this interim analysis are encouraging and met our decision criteria to stop enrollment in this study and progress to a pivotal Phase 2/3 trial,” said David Rodman, M.D., executive vice president of research and development of ProQR. “We observed a clinically meaningful improvement in vision in the treated eye as measured by both mechanistic and potential registration endpoints. Consistent with predictions based on our patient derived optic-cup models, improvement in visual function was observed as early as two months after treatment and was maximal and stable by three months and thereafter. We are very grateful to the study participants, their caregivers, and the investigators and their staff for the support in the development of QR-110 in this trial.”
Thaddeus P. Dryja, M.D., professor of ophthalmology at Harvard Medical School and Massachusetts Eye and Ear and member of the National Academy of Sciences, commented, “These results are the first human data to evaluate the clinical utility of RNA-based therapeutics in a human photoreceptor disease, particularly one with a severe unmet medical need. While a confirmatory trial will be required to establish the full potential of QR-110 in LCA10, these results suggest that therapeutic oligonucleotides have the potential to be broadly applicable to a wide spectrum of inherited retinal disorders.”
Based on the emerging findings from the Phase 1/2 trial, the Company agreed with the FDA to submit a protocol to progress to a pivotal Phase 2/3 trial. In light thereof, the originally planned interim analysis at six months treatment was accelerated to the point when eight patients had reached three months of treatment. Given comparable activity was observed in the first two dose levels, the trial did not escalate up to the high dose and trial enrollment has stopped, in anticipation of the start of a Phase 2/3 trial.
Results from the interim analysis
Efficacy data: Approximately 60% of subjects showed a clinically meaningful response in visual acuity and mobility course endpoints at three months of treatment and there was general concordance across the endpoints. Efficacy signals were observed within two months with maximal benefits seen within two to three months post treatment initiation. A secondary analysis assessing all available data demonstrated that observed effects on efficacy were durable beyond three months.
Visual acuity: In the majority of patients, there was a substantive overall improvement in best corrected visual acuity (BCVA) as assessed by the Berkeley Rudimentary Vision Test (BRVT) and the Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart. At three months of treatment, the mean improvement (and standard error of mean, SEM) was -0.67 LogMAR (SEM 0.32) with 62.5% of subjects showing an improvement of greater than -0.3 LogMAR from baseline, which is considered clinically meaningful. The mean change in the contralateral eye was 0.02 LogMAR (SEM 0.05).
Mobility course: Effects on visual acuity correlated with effects on mobility. In the majority of patients there was a substantive overall improvement in functional visual performance as assessed using a series of mobility courses at increasing difficulty and multiple light intensities. At three months of treatment, the mean improvement in navigating the mobility course was 2.6 levels (SEM 1.2) with 57.1% of subjects improving by more than 2.0 levels, which is regarded as clinically meaningful. The mean change in the contralateral eye was 1.36 (SEM 1.04).
Full field stimulus test (FST): Improvements in visual function were supported by a meaningful increase in the ability to detect flashes of red or blue light as determined by the FST. After three months of treatment mean improvement in red light sensitivity was -0.74 log Cd/m2 (SEM 0.35) and improvement in blue light sensitivity was -0.91 log Cd/m2 (SEM 0.38).
Ocular Instability (OCI): Additionally, the majority of patients improved on nystagmus (involuntary eye movements in low vision patients), with a mean change of log -0.14 mm (SEM 0.08) in OCI.
Safety: Out of the 10 subjects dosed in the study, one subject has received all four doses and three have received three doses, representing a combined total of more than 1,500 treatment days. So far QR-110 was well tolerated with no serious adverse events related to treatment or procedure. All data and safety monitoring committee (DSMC) reviews were completed with no restrictions on further dose escalation or pediatric dosing.
Start of Phase 2/3 pivotal “ILLUMINATE” trial
The Company has agreed with the FDA to submit a protocol to start a Phase 2/3 trial that could serve as the sole registration trial, to be called “ILLUMINATE”. The preliminary design for “ILLUMINATE” is a double-blind, controlled, 12-month study. The trial is expected to initially enroll 30-40 patients with LCA10 due to one or two copies of the p.Cys998X mutation and could be adaptively repowered. The primary endpoints in this trial are expected to include the mobility course and visual acuity, among others. The trial is expected to be conducted at centers in North America and select European countries. Pending completing discussions on the design of the study with the FDA in 2018, the trial is expected to start in the first half of 2019. In parallel to the pivotal Phase 2/3 trial, the Company plans to start a trial in patients <6 years old.
Stimulating the early phase in Organ-on-Chip technology development
The Top Sector Life Sciences & Health and hDMT join forces on the research and development of organ-on-chip technology. This field of technology offers our society and healthcare system great opportunities to treat chronic diseases in a personalized way. In addition, the technology can lead to the reduction of animal experiments by development of alternative preclinical test models. To enhance the R&D and develop organ-on-chip showcases the Top Sector and hDMT established the new Health~Holland Organ-on-Chip Showcases (HHOOCS) programme.
New programme and call
Within this new HHOOCS programme, interdisciplinary consortia of companies, recognised knowledge institutions, patient organisations and/or health foundations are invited to apply for financial support to develop an Organ-on-Chip showcase that integrates human stem cell or organoid in vitro cultures and/or microfluidics technology. The financial support is part of the public-private partnership (PPP) allowance of the Top Sector. The programme aims at developing showcases for specific organ or tissue functionalities which qualify for further research funding. The deadline for submission is 14 January 2019.
Dutch Startup Nestegg Biotech has been approved for a subordinated loan from Rabobank through their “AIL” program. The loans total €150.000 and will be used to bring new “Lab Automation” products to markets serving Dutch and Flemish research institutes and universities this fiscal year. Nestegg Biotech BV was assisted in applying for the loans by the Manager of Public Funding at the Brightlands Innovation Factory, Hugo Nikkel. Brightlands continues to support the development of Nestegg Biotech’s goal of bringing “enhanced automation” to laboratories performing cutting-edge research across Europe.
The Rabobank Achtergestelde Innovatie Lening or “AIL” program is provided to help with the financing of innovations. It is intended for funding early stage developments in within themes including smart technology for renewables, vitality, and sustainable solutions within the healthcare sector such as medical tech or biopharmaceuticals. More information about the program can be found here.
Obruza is a novel automated system provided by Nestegg Biotech to allow researchers to automate experiments in the fields of regenerative medicine, cell culture, drug development, and diagnostics. Nestegg Biotech has facilities on the Brightlands Maastrich Health Campus, in the southern Dutch province of Limburg. Nestegg Biotech expects to achieve validation of the Obruza system this fall in tandem with their initial partner the MERLN Institute for Regenerative Medicine in Maastricht. Announcement of new customers and partners is expected before the end of the calendar year.
HollandBIO is blij met de aanpassing van Besluit GGO 2013, recent aangekondigd in het Staatsblad, omdat deze het werken met genetisch gemodificeerde organismen (GMO’s) sneller en makkelijker maakt. De afgelopen jaren trok HollandBIO samen met het Ministerie van Infrastructuur en Waterstaat (IenW) en andere stakeholders op om deze verbetering van de regelgeving te realiseren. Dankzij de aanpassing komen onnodige wachttijden te vervallen en is het voor bedrijven makkelijker om een kennisgeving of vergunning voor het werken met GMO’s aan te vragen.
HollandBIO ziet de wijziging als een waardevolle eerste stap in de goede richting en zo ziet de Staatssecretaris van IenW het ook. De Staatssecretaris werkt graag met HollandBIO verder aan onze andere aanpassingsvoorstellen, zoals het beoordelen van gentherapeutische toepassingen onder ingeperkt gebruik, het laten vervallen van een vergunning voor klinische proeven met geautoriseerde producten en het verhogen van de volumegrens voor bioreactoren. Wij nemen deze uitnodiging natuurlijk graag aan.
Vitalnext publiceerde positieve resultaten van een onlangs afgeronde klinische studie naar het effect van een innovatieve medische voeding (Vital01) bij de behandeling van ondervoede mensen. De resultaten werden gepresenteerd op een congres in Madrid (the 40th Congress of ‘the European Society for Clinical Nutrition and Metabolism’).
In de klinische studie werd Vital01, een nieuwe en innovatieve medische voeding, vergeleken met een standaardproduct dat veel gebruikt wordt in Nederland en dezelfde hoeveelheid eiwit en energie bevatte. 82 thuiswonende ouderen, die ondervoed waren of een sterk verhoogd risico op ondervoeding hadden, werden willekeurig ingedeeld in één van beide groepen en gedurende een periode van 12 weken nauwkeurig gevolgd.
Het belangrijkste resultaat van de studie is dat mensen uit de Vital01 groep sneller gingen lopen dan mensen uit de controle-groep. Dit gold zowel voor een korte afstand (4m) als voor een langere afstand (400m). Eerdere onderzoeken hebben uitvoerig aangetoond dat loopsnelheid bij ondervoede oudere mensen direct gecorreleerd is aan hun algemene gezondheidsstatus en aan kwaliteit van leven. Voorlopige analyses tonen aan dat naast een mogelijke bijdrage van de toegenomen spiermassa het verschil in loopsnelheid vooral kan worden verklaard door een meer efficiënt gebruik van energie door de spieren. Dit wordt veroorzaakt door de specifieke samenstelling van Vital01.
Ondervoeding komt veel voor bij oudere mensen en is direct gerelateerd is aan langer verblijf in het ziekenhuis, een toegenomen sterftekans en hoge maatschappelijke kosten. Vitalnext heeft Vital01 ontwikkeld met als doel om eiwit efficiënt om te zetten in spiermassa om zo de fysieke conditie en mobiliteit van patiënten te verbeteren. Vital01 is een volledige voeding in poedervorm die gemengd kan worden met gangbare vloeibare en vaste voedingsmiddelen al naar gelang de voorkeuren van de patiënt.
Rein Strijker, oprichter en CEO van Vitalnext merkt op: “Deze resultaten laten zien dat Vital01 aanzienlijke voordelen heeft over producten die nu standaard worden gebruikt voor deze patiënten. Met name verbetering van de loopsnelheid is heel relevant voor patiënten die ondervoed zijn. We zijn erg blij dat we door deze ontwikkeling nieuwe en sterk verbeterde behandelingen kunnen bieden aan deze patiënten.”
Rudy Mareel, voorzitter van de Raad van Commissarissen van Vitalnext, benadrukt de verbetering van klinische effecten voor patiënten: “Tot op heden ging medische voeding over calorieën en gewichtstoename met weinig innovatie behalve op het gebied van smaak, textuur en voedingsopname. De impact op loopsnelheid brengt ons nu een stap verder, namelijk een directe verbetering van de kwaliteit van leven. Dit is daarom een geweldig moment voor de industrie, voor Vitalnext en, vooral, voor de patiënten”.
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00hollandbiohttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svghollandbio2018-09-03 12:14:222018-09-04 13:57:45Vitalnext presenteert positieve resultaten in klinische studie naar ondervoeding← #nieuws
While research groups in China have already started testing CRISPR in humans, CRISPR Therapeutics and Vertex Pharmaceuticals are the first companies to sponsor a human trial of the gene editing technology. The trial will take place at a single site in Germany and will test a gene therapy in patients with beta thalassemia.
Vertex licensed CTX001, an autologous gene-edited hematopoietic stem cell therapy, from CRISPR in December. It was the first CRISPR-based treatment to come out of a four-year, $105 million deal the pair struck in 2015. At the time, Vertex paid up $75 million in cash and took a $30 million stake in CRISPR Therapeutics in exchange for the right to license up to six gene-editing programs. CTX001 is being developed for the blood disorders sickle cell disease and beta thalassemia.
Both disorders are caused by mutations in the beta-globin gene, which codes for a part of hemoglobin, the oxygen-carrying component of red blood cells. This results in missing or defective hemoglobin. CTX001 was developed on the knowledge that fetal hemoglobin—found in newborn babies but later replaced by adult hemoglobin—can be protective in adults who have blood disorders.
CTX001 uses CRISPR gene-editing ex vivo—that is, outside the body. A patient’s cells are harvested and edited to increase fetal hemoglobin levels in the patient’s blood cells. The edited cells are then infused back into the patient where they are expected to produce blood cells with fetal hemoglobin and compensate for defective adult hemoglobin.
The new trial will test CTX001 in up to 12 adult patients who have transfusion-dependent beta thalassemia, according to an announcement on Clinicaltrials.gov. It will take place at a single hospital in Regensburg, Germany.
“CRISPR Therapeutics and Vertex are advancing CTX001 as the first gene editing treatment for both sickle cell disease and beta thalassemia using the CRISPR/Cas9 technology, and have now opened the beta thalassemia study for enrollment in a Phase 1/2 trial in Europe,” said a CRISPR Therapeutics spokesperson via email. “This is one important step of many toward bringing the promise of this new technology to patients with serious diseases like SCD and beta thalassemia, and we are thrilled to be at the forefront of what we believe may be a fundamental change in the treatment of disease.”
The partners have been planning a U.S. trial testing the treatment in sickle cell disease, but its IND ran into an FDA clinical hold in May. Details were few and far between and shares in CRISPR slipped 15% at the time.
For a time, it looked like Editas Medicine would be the first to launch a human trial, with plans to start testing a CRISPR treatment for a rare form of blindness in 2017. Manufacturing issues delayed the timeline to 2018, with CEO Katrine Bosley saying in the company’s second-quarter update that the IND filing is slated for October.
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00hollandbiohttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svghollandbio2018-08-31 17:36:122018-09-04 17:39:49CRISPR Therapeutics and Vertex start first company-backed human CRISPR trial← #nieuws
Facio Therapies has selected a second series of potential candidates for FSHD drug development. This series encompasses a family of novel small-molecule compounds that repress DUX4 by engaging a molecular target that differs from the target of Facio’s first series of potential drug development candidates.
The key event in FSHD is the undue production of the DUX4 protein in skeletal muscle. DUX4 sets in motion a cascade of biochemical events that eventually result in the devastating effects of FSHD. In people without FSHD, the production of DUX4 in skeletal muscle is repressed by regulatory mechanisms. Facio’s single goal is to develop therapies that restore this repression as much as possible.
In January 2018, Facio announced the selection of a first series of potential FSHD drug development candidates. Facio pursues additional series because the severity and course of FSHD are highly variable. This makes it likely that more than one therapeutic drug will be needed to treat all people with FSHD. In order to address this issue head-on, Facio is building a portfolio of product candidates. As an additional advantage, the portfolio approach helps improve Facio’s overall chance of success (or, as the saying goes, provides “multiple shots on goal”).
David Dasberg, Facio’s Managing Director, pointed out that the compounds in both Facio’s first and second series repress DUX4 expression in a concentration-dependent, drug-like fashion without impairing the mechanism underlying muscle repair and regeneration in FSHD. “Importantly”, he added, “the compounds in our second series do so by engaging a different target. This shows the power of our strategy to apply a unique drug screening platform to identify compounds that do repress DUX4, rather than compounds that may or may not repress DUX4 by fitting one of the many possible hypotheses about how DUX4 expression is regulated.”
Looking ahead, David said: “We plan to unravel the mode of action of our second compound series over the next months. Meantime, we anticipate announcing progress with our first compound series in the near future.”
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00hollandbiohttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svghollandbio2018-08-30 13:50:292018-09-04 13:54:34Facio broadens portfolio of potential drug development candidates← #nieuws
There is still a lot of unmet medical need that requires the combined effort and support of all stakeholders to develop new breakthrough therapies. Developing and getting these innovative therapies to patients results in growing pressure to healthcare budgets. At the same time, these healthcare systems need to remain affordable and accessible to all patients. In the past decade, pharmaceutical companies have experimented with innovative pricing schemes to ensure affordability and accessibility.
Despite these efforts, we still find ourselves in a deadlock in the pricing debate. It is time that pharma and payers start working together to find real solutions and to ensure patients have access to the best possible therapies for a fair price for all stakeholders.
Vintura, in collaboration with Lieven Annemans, professor in health economics at UGent, developed a framework to help pharma and payers start a new dialogue and explore where they might find common ground.
The framework provides a step-by-step approach for pharmaceutical companies and payers:
Step 1: come to an agreement on what constitutes value
Step 2: come to an understanding of the pricing criteria
Step 3: agree on the price dynamic over time
Step 4: agree on risk sharing and the payment scheme
This framework will enable pharmaceutical companies and payers to start a structured dialogue and explore where they might find common ground. The ultimate goal is to secure innovation at a sustainable cost and a “fair” price for all stakeholders.
Co-author Lieven Annemans, professor in health-economics, about this publication: “It is time that pharma and payers start working together on pharma pricing to find solutions that balance the needs of pharmaceutical companies, payers and society. I am proud to be co-author of the attached paper.”
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00hollandbiohttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svghollandbio2018-08-28 15:07:052018-08-28 15:07:05White paper ‘Towards a constructive dialogue on pharmaceutical pricing’← #nieuws
We leven in de eeuw van life sciences: technologische ontwikkelingen maken oplossingen mogelijk die onze gezondheidszorg gigantisch gaan veranderen. De ontwikkelingen buitelen over elkaar heen. Onderzoeksbureau Motivaction onderzoekt of er behoefte bestaat aan een onafhankelijk journalistiek medium dat zich speciaal richt op mensen die werken in of met biotech, medtech, farma en e-health. Doe hier mee aan het onderzoek
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00hollandbiohttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svghollandbio2018-08-28 14:48:352018-08-28 14:54:41Enquête over nieuw journalistiek platform voor life sciences← #nieuws
Op uitnodiging van het ministerie van VWS reageerde HollandBIO vorige week op de voorgenomen wijziging van de Wet Geneesmiddelenprijzen, de WGP. Het vervangen van referentieland Duitsland door Noorwegen realiseert jaarlijks een besparing van 239 miljoen euro, zo becijfert de Stichting Farmaceutische Kengetallen. De maatregel is het zoveelste lapmiddel om de zorgkosten te beheersen door minimalisatie van de geneesmiddelenuitgaven. Geneesmiddelen fungeren zo als kiloknallers van de zorg, in plaats van als hofleveranciers voor volksgezondheid. In onze reactie breken we een lans voor duurzame oplossingen waarbij gzondheidswinst, innovatie en betaalbaarheid hand in hand gaan. Je leest onze brief hier.
https://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svg00hollandbiohttps://www.hollandbio.nl/wp-content/uploads/2023/08/HollandBIO_logo.svghollandbio2018-08-28 14:13:482018-08-28 14:16:45Geneesmiddelen: van kiloknaller naar hofleverancier
Positive interim results for ProQR’s QR-110
GezondheidProQR Therapeutics, a company dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases, announced results from a planned interim analysis of its Phase 1/2 trial of QR-110 in patients with Leber’s congenital amaurosis 10 (LCA10) due to the p.Cys998X mutation in the CEP290 gene. LCA10 typically leads to childhood blindness and has no available treatment options. In the trial, QR-110 demonstrated rapid and sustained improvement in vision in patients with LCA10, as measured by visual acuity and the mobility course performance, as well as being well-tolerated with no serious adverse events recorded. Results from this interim analysis were presented earlier today at the Retinal Degeneration 2018 meeting in Killarney, Ireland, by principal investigator Artur Cideciyan, Ph.D., research professor of ophthalmology at the Scheie Eye Institute, University of Pennsylvania.
“The results of this interim analysis are encouraging and met our decision criteria to stop enrollment in this study and progress to a pivotal Phase 2/3 trial,” said David Rodman, M.D., executive vice president of research and development of ProQR. “We observed a clinically meaningful improvement in vision in the treated eye as measured by both mechanistic and potential registration endpoints. Consistent with predictions based on our patient derived optic-cup models, improvement in visual function was observed as early as two months after treatment and was maximal and stable by three months and thereafter. We are very grateful to the study participants, their caregivers, and the investigators and their staff for the support in the development of QR-110 in this trial.”
Thaddeus P. Dryja, M.D., professor of ophthalmology at Harvard Medical School and Massachusetts Eye and Ear and member of the National Academy of Sciences, commented, “These results are the first human data to evaluate the clinical utility of RNA-based therapeutics in a human photoreceptor disease, particularly one with a severe unmet medical need. While a confirmatory trial will be required to establish the full potential of QR-110 in LCA10, these results suggest that therapeutic oligonucleotides have the potential to be broadly applicable to a wide spectrum of inherited retinal disorders.”
Based on the emerging findings from the Phase 1/2 trial, the Company agreed with the FDA to submit a protocol to progress to a pivotal Phase 2/3 trial. In light thereof, the originally planned interim analysis at six months treatment was accelerated to the point when eight patients had reached three months of treatment. Given comparable activity was observed in the first two dose levels, the trial did not escalate up to the high dose and trial enrollment has stopped, in anticipation of the start of a Phase 2/3 trial.
Results from the interim analysis
Efficacy data: Approximately 60% of subjects showed a clinically meaningful response in visual acuity and mobility course endpoints at three months of treatment and there was general concordance across the endpoints. Efficacy signals were observed within two months with maximal benefits seen within two to three months post treatment initiation. A secondary analysis assessing all available data demonstrated that observed effects on efficacy were durable beyond three months.
Visual acuity: In the majority of patients, there was a substantive overall improvement in best corrected visual acuity (BCVA) as assessed by the Berkeley Rudimentary Vision Test (BRVT) and the Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart. At three months of treatment, the mean improvement (and standard error of mean, SEM) was -0.67 LogMAR (SEM 0.32) with 62.5% of subjects showing an improvement of greater than -0.3 LogMAR from baseline, which is considered clinically meaningful. The mean change in the contralateral eye was 0.02 LogMAR (SEM 0.05).
Mobility course: Effects on visual acuity correlated with effects on mobility. In the majority of patients there was a substantive overall improvement in functional visual performance as assessed using a series of mobility courses at increasing difficulty and multiple light intensities. At three months of treatment, the mean improvement in navigating the mobility course was 2.6 levels (SEM 1.2) with 57.1% of subjects improving by more than 2.0 levels, which is regarded as clinically meaningful. The mean change in the contralateral eye was 1.36 (SEM 1.04).
Full field stimulus test (FST): Improvements in visual function were supported by a meaningful increase in the ability to detect flashes of red or blue light as determined by the FST. After three months of treatment mean improvement in red light sensitivity was -0.74 log Cd/m2 (SEM 0.35) and improvement in blue light sensitivity was -0.91 log Cd/m2 (SEM 0.38).
Ocular Instability (OCI): Additionally, the majority of patients improved on nystagmus (involuntary eye movements in low vision patients), with a mean change of log -0.14 mm (SEM 0.08) in OCI.
Safety: Out of the 10 subjects dosed in the study, one subject has received all four doses and three have received three doses, representing a combined total of more than 1,500 treatment days. So far QR-110 was well tolerated with no serious adverse events related to treatment or procedure. All data and safety monitoring committee (DSMC) reviews were completed with no restrictions on further dose escalation or pediatric dosing.
Start of Phase 2/3 pivotal “ILLUMINATE” trial
The Company has agreed with the FDA to submit a protocol to start a Phase 2/3 trial that could serve as the sole registration trial, to be called “ILLUMINATE”. The preliminary design for “ILLUMINATE” is a double-blind, controlled, 12-month study. The trial is expected to initially enroll 30-40 patients with LCA10 due to one or two copies of the p.Cys998X mutation and could be adaptively repowered. The primary endpoints in this trial are expected to include the mobility course and visual acuity, among others. The trial is expected to be conducted at centers in North America and select European countries. Pending completing discussions on the design of the study with the FDA in 2018, the trial is expected to start in the first half of 2019. In parallel to the pivotal Phase 2/3 trial, the Company plans to start a trial in patients <6 years old.
Source: ProQR
Health~Holland opens call for Organ-on-Chip showcases
InnovatieklimaatStimulating the early phase in Organ-on-Chip technology development
The Top Sector Life Sciences & Health and hDMT join forces on the research and development of organ-on-chip technology. This field of technology offers our society and healthcare system great opportunities to treat chronic diseases in a personalized way. In addition, the technology can lead to the reduction of animal experiments by development of alternative preclinical test models. To enhance the R&D and develop organ-on-chip showcases the Top Sector and hDMT established the new Health~Holland Organ-on-Chip Showcases (HHOOCS) programme.
New programme and call
Within this new HHOOCS programme, interdisciplinary consortia of companies, recognised knowledge institutions, patient organisations and/or health foundations are invited to apply for financial support to develop an Organ-on-Chip showcase that integrates human stem cell or organoid in vitro cultures and/or microfluidics technology. The financial support is part of the public-private partnership (PPP) allowance of the Top Sector. The programme aims at developing showcases for specific organ or tissue functionalities which qualify for further research funding. The deadline for submission is 14 January 2019.
Want to join?
Interested in the research programme and the requirements for application? Please visit Health~Holland’s funding page.
Dutch Startup Nestegg Biotech Approved for Innovation Loan
InnovatieklimaatDutch Startup Nestegg Biotech has been approved for a subordinated loan from Rabobank through their “AIL” program. The loans total €150.000 and will be used to bring new “Lab Automation” products to markets serving Dutch and Flemish research institutes and universities this fiscal year. Nestegg Biotech BV was assisted in applying for the loans by the Manager of Public Funding at the Brightlands Innovation Factory, Hugo Nikkel. Brightlands continues to support the development of Nestegg Biotech’s goal of bringing “enhanced automation” to laboratories performing cutting-edge research across Europe.
The Rabobank Achtergestelde Innovatie Lening or “AIL” program is provided to help with the financing of innovations. It is intended for funding early stage developments in within themes including smart technology for renewables, vitality, and sustainable solutions within the healthcare sector such as medical tech or biopharmaceuticals. More information about the program can be found here.
Obruza is a novel automated system provided by Nestegg Biotech to allow researchers to automate experiments in the fields of regenerative medicine, cell culture, drug development, and diagnostics. Nestegg Biotech has facilities on the Brightlands Maastrich Health Campus, in the southern Dutch province of Limburg. Nestegg Biotech expects to achieve validation of the Obruza system this fall in tandem with their initial partner the MERLN Institute for Regenerative Medicine in Maastricht. Announcement of new customers and partners is expected before the end of the calendar year.
Source: Brightlands
Mooi nieuws: aanvragen GM-vergunning sneller en makkelijker
Wereld mét toekomst, Hollandbio, Voedsel en materialenHollandBIO is blij met de aanpassing van Besluit GGO 2013, recent aangekondigd in het Staatsblad, omdat deze het werken met genetisch gemodificeerde organismen (GMO’s) sneller en makkelijker maakt. De afgelopen jaren trok HollandBIO samen met het Ministerie van Infrastructuur en Waterstaat (IenW) en andere stakeholders op om deze verbetering van de regelgeving te realiseren. Dankzij de aanpassing komen onnodige wachttijden te vervallen en is het voor bedrijven makkelijker om een kennisgeving of vergunning voor het werken met GMO’s aan te vragen.
HollandBIO ziet de wijziging als een waardevolle eerste stap in de goede richting en zo ziet de Staatssecretaris van IenW het ook. De Staatssecretaris werkt graag met HollandBIO verder aan onze andere aanpassingsvoorstellen, zoals het beoordelen van gentherapeutische toepassingen onder ingeperkt gebruik, het laten vervallen van een vergunning voor klinische proeven met geautoriseerde producten en het verhogen van de volumegrens voor bioreactoren. Wij nemen deze uitnodiging natuurlijk graag aan.
Lees hier de aankondiging.
Vitalnext presenteert positieve resultaten in klinische studie naar ondervoeding
Gezondheid, Voedsel en materialenVitalnext publiceerde positieve resultaten van een onlangs afgeronde klinische studie naar het effect van een innovatieve medische voeding (Vital01) bij de behandeling van ondervoede mensen. De resultaten werden gepresenteerd op een congres in Madrid (the 40th Congress of ‘the European Society for Clinical Nutrition and Metabolism’).
In de klinische studie werd Vital01, een nieuwe en innovatieve medische voeding, vergeleken met een standaardproduct dat veel gebruikt wordt in Nederland en dezelfde hoeveelheid eiwit en energie bevatte. 82 thuiswonende ouderen, die ondervoed waren of een sterk verhoogd risico op ondervoeding hadden, werden willekeurig ingedeeld in één van beide groepen en gedurende een periode van 12 weken nauwkeurig gevolgd.
Het belangrijkste resultaat van de studie is dat mensen uit de Vital01 groep sneller gingen lopen dan mensen uit de controle-groep. Dit gold zowel voor een korte afstand (4m) als voor een langere afstand (400m). Eerdere onderzoeken hebben uitvoerig aangetoond dat loopsnelheid bij ondervoede oudere mensen direct gecorreleerd is aan hun algemene gezondheidsstatus en aan kwaliteit van leven. Voorlopige analyses tonen aan dat naast een mogelijke bijdrage van de toegenomen spiermassa het verschil in loopsnelheid vooral kan worden verklaard door een meer efficiënt gebruik van energie door de spieren. Dit wordt veroorzaakt door de specifieke samenstelling van Vital01.
Ondervoeding komt veel voor bij oudere mensen en is direct gerelateerd is aan langer verblijf in het ziekenhuis, een toegenomen sterftekans en hoge maatschappelijke kosten. Vitalnext heeft Vital01 ontwikkeld met als doel om eiwit efficiënt om te zetten in spiermassa om zo de fysieke conditie en mobiliteit van patiënten te verbeteren. Vital01 is een volledige voeding in poedervorm die gemengd kan worden met gangbare vloeibare en vaste voedingsmiddelen al naar gelang de voorkeuren van de patiënt.
Rein Strijker, oprichter en CEO van Vitalnext merkt op: “Deze resultaten laten zien dat Vital01 aanzienlijke voordelen heeft over producten die nu standaard worden gebruikt voor deze patiënten. Met name verbetering van de loopsnelheid is heel relevant voor patiënten die ondervoed zijn. We zijn erg blij dat we door deze ontwikkeling nieuwe en sterk verbeterde behandelingen kunnen bieden aan deze patiënten.”
Rudy Mareel, voorzitter van de Raad van Commissarissen van Vitalnext, benadrukt de verbetering van klinische effecten voor patiënten: “Tot op heden ging medische voeding over calorieën en gewichtstoename met weinig innovatie behalve op het gebied van smaak, textuur en voedingsopname. De impact op loopsnelheid brengt ons nu een stap verder, namelijk een directe verbetering van de kwaliteit van leven. Dit is daarom een geweldig moment voor de industrie, voor Vitalnext en, vooral, voor de patiënten”.
Bron: VitalNext
CRISPR Therapeutics and Vertex start first company-backed human CRISPR trial
GezondheidWhile research groups in China have already started testing CRISPR in humans, CRISPR Therapeutics and Vertex Pharmaceuticals are the first companies to sponsor a human trial of the gene editing technology. The trial will take place at a single site in Germany and will test a gene therapy in patients with beta thalassemia.
Vertex licensed CTX001, an autologous gene-edited hematopoietic stem cell therapy, from CRISPR in December. It was the first CRISPR-based treatment to come out of a four-year, $105 million deal the pair struck in 2015. At the time, Vertex paid up $75 million in cash and took a $30 million stake in CRISPR Therapeutics in exchange for the right to license up to six gene-editing programs. CTX001 is being developed for the blood disorders sickle cell disease and beta thalassemia.
Both disorders are caused by mutations in the beta-globin gene, which codes for a part of hemoglobin, the oxygen-carrying component of red blood cells. This results in missing or defective hemoglobin. CTX001 was developed on the knowledge that fetal hemoglobin—found in newborn babies but later replaced by adult hemoglobin—can be protective in adults who have blood disorders.
CTX001 uses CRISPR gene-editing ex vivo—that is, outside the body. A patient’s cells are harvested and edited to increase fetal hemoglobin levels in the patient’s blood cells. The edited cells are then infused back into the patient where they are expected to produce blood cells with fetal hemoglobin and compensate for defective adult hemoglobin.
The new trial will test CTX001 in up to 12 adult patients who have transfusion-dependent beta thalassemia, according to an announcement on Clinicaltrials.gov. It will take place at a single hospital in Regensburg, Germany.
“CRISPR Therapeutics and Vertex are advancing CTX001 as the first gene editing treatment for both sickle cell disease and beta thalassemia using the CRISPR/Cas9 technology, and have now opened the beta thalassemia study for enrollment in a Phase 1/2 trial in Europe,” said a CRISPR Therapeutics spokesperson via email. “This is one important step of many toward bringing the promise of this new technology to patients with serious diseases like SCD and beta thalassemia, and we are thrilled to be at the forefront of what we believe may be a fundamental change in the treatment of disease.”
The partners have been planning a U.S. trial testing the treatment in sickle cell disease, but its IND ran into an FDA clinical hold in May. Details were few and far between and shares in CRISPR slipped 15% at the time.
For a time, it looked like Editas Medicine would be the first to launch a human trial, with plans to start testing a CRISPR treatment for a rare form of blindness in 2017. Manufacturing issues delayed the timeline to 2018, with CEO Katrine Bosley saying in the company’s second-quarter update that the IND filing is slated for October.
Source: FierceBiotech
Facio broadens portfolio of potential drug development candidates
GezondheidFacio Therapies has selected a second series of potential candidates for FSHD drug development. This series encompasses a family of novel small-molecule compounds that repress DUX4 by engaging a molecular target that differs from the target of Facio’s first series of potential drug development candidates.
The key event in FSHD is the undue production of the DUX4 protein in skeletal muscle. DUX4 sets in motion a cascade of biochemical events that eventually result in the devastating effects of FSHD. In people without FSHD, the production of DUX4 in skeletal muscle is repressed by regulatory mechanisms. Facio’s single goal is to develop therapies that restore this repression as much as possible.
In January 2018, Facio announced the selection of a first series of potential FSHD drug development candidates. Facio pursues additional series because the severity and course of FSHD are highly variable. This makes it likely that more than one therapeutic drug will be needed to treat all people with FSHD. In order to address this issue head-on, Facio is building a portfolio of product candidates. As an additional advantage, the portfolio approach helps improve Facio’s overall chance of success (or, as the saying goes, provides “multiple shots on goal”).
David Dasberg, Facio’s Managing Director, pointed out that the compounds in both Facio’s first and second series repress DUX4 expression in a concentration-dependent, drug-like fashion without impairing the mechanism underlying muscle repair and regeneration in FSHD. “Importantly”, he added, “the compounds in our second series do so by engaging a different target. This shows the power of our strategy to apply a unique drug screening platform to identify compounds that do repress DUX4, rather than compounds that may or may not repress DUX4 by fitting one of the many possible hypotheses about how DUX4 expression is regulated.”
Looking ahead, David said: “We plan to unravel the mode of action of our second compound series over the next months. Meantime, we anticipate announcing progress with our first compound series in the near future.”
Source: Facio Therapies
White paper ‘Towards a constructive dialogue on pharmaceutical pricing’
InnovatieklimaatThere is still a lot of unmet medical need that requires the combined effort and support of all stakeholders to develop new breakthrough therapies. Developing and getting these innovative therapies to patients results in growing pressure to healthcare budgets. At the same time, these healthcare systems need to remain affordable and accessible to all patients. In the past decade, pharmaceutical companies have experimented with innovative pricing schemes to ensure affordability and accessibility.
Despite these efforts, we still find ourselves in a deadlock in the pricing debate. It is time that pharma and payers start working together to find real solutions and to ensure patients have access to the best possible therapies for a fair price for all stakeholders.
Vintura, in collaboration with Lieven Annemans, professor in health economics at UGent, developed a framework to help pharma and payers start a new dialogue and explore where they might find common ground.
The framework provides a step-by-step approach for pharmaceutical companies and payers:
This framework will enable pharmaceutical companies and payers to start a structured dialogue and explore where they might find common ground. The ultimate goal is to secure innovation at a sustainable cost and a “fair” price for all stakeholders.
Download your copy of the white paper here.
Co-author Lieven Annemans, professor in health-economics, about this publication: “It is time that pharma and payers start working together on pharma pricing to find solutions that balance the needs of pharmaceutical companies, payers and society. I am proud to be co-author of the attached paper.”
Enquête over nieuw journalistiek platform voor life sciences
InnovatieklimaatWe leven in de eeuw van life sciences: technologische ontwikkelingen maken oplossingen mogelijk die onze gezondheidszorg gigantisch gaan veranderen. De ontwikkelingen buitelen over elkaar heen. Onderzoeksbureau Motivaction onderzoekt of er behoefte bestaat aan een onafhankelijk journalistiek medium dat zich speciaal richt op mensen die werken in of met biotech, medtech, farma en e-health. Doe hier mee aan het onderzoek
Geneesmiddelen: van kiloknaller naar hofleverancier
Hollandbio, InnovatieklimaatOp uitnodiging van het ministerie van VWS reageerde HollandBIO vorige week op de voorgenomen wijziging van de Wet Geneesmiddelenprijzen, de WGP. Het vervangen van referentieland Duitsland door Noorwegen realiseert jaarlijks een besparing van 239 miljoen euro, zo becijfert de Stichting Farmaceutische Kengetallen. De maatregel is het zoveelste lapmiddel om de zorgkosten te beheersen door minimalisatie van de geneesmiddelenuitgaven. Geneesmiddelen fungeren zo als kiloknallers van de zorg, in plaats van als hofleveranciers voor volksgezondheid. In onze reactie breken we een lans voor duurzame oplossingen waarbij gzondheidswinst, innovatie en betaalbaarheid hand in hand gaan. Je leest onze brief hier.