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CHMP Backs Expanded Use For Amgen’s Prolia To Patients With Glucocorticoid-Induced Osteoporosis

Amgen announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion for the marketing authorization of Prolia for the treatment of bone loss associated with long-term systemic glucocorticoid therapy in adult patients at increased risk of fracture.

“Today’s positive opinion by the CHMP is an important step for Prolia in helping patients suffering from bone loss associated with systemic glucocorticoid therapy,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “Chronic use of oral glucocorticoids has been associated with an increase in spine and hip fractures,1 and, if approved, an expanded use of Prolia will provide patients and physicians across much of Europe with a new treatment option for this serious condition.”

Glucocorticoid medications, which are used to treat many inflammatory conditions such as chronic obstructive pulmonary disorder (COPD), asthma, multiple sclerosis and rheumatoid arthritis, can cause significant side effects, including bone loss.

The CHMP recommendation is supported by a Phase 3 randomized, double-blind, double-dummy, active-controlled study evaluating the safety and efficacy of Prolia compared with risedronate in patients receiving glucocorticoid treatment.4 The study included two patient groups: those on sustained glucocorticoid therapy and those newly initiating glucocorticoid therapy. The study met the primary endpoint (percent change from baseline in lumbar spine bone mass density [BMD] at 12 months, assessing non-inferiority) and all secondary endpoints (the percent changes from baseline in lumbar spine and total hip BMD at 12 and 24 months, assessing superiority). Study results showed that, in patients on sustained glucocorticoid therapy, Prolia treatment led to greater gains in BMD, compared with risedronate, both at the lumbar spine (4.4 percent versus 2.3 percent, respectively) and total hip (2.1 percent versus 0.6 percent, respectively). Similarly, in patients newly initiating glucocorticoid therapy, Prolia treatment led to greater increases in BMD, compared with risedronate, both at the lumbar spine (3.8 percent versus 0.8 percent, respectively) and total hip (1.7 percent versus 0.2 percent, respectively).

Adverse events and serious adverse events were similar between treatment groups and consistent with the known safety profile of Prolia. No serious adverse events were reported with a subject incidence of two percent or greater in either treatment group.

The CHMP positive opinion will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU). Norway, Iceland and Liechtenstein, as members of the European Economic Area (EEA), will take corresponding decisions based on the decision of the EC.

The U.S. Food and Drug Administration (FDA) is currently reviewing a supplemental Biologics License Application for this expanded indication and has set a Prescription Drug User Fee Act (PDUFA) action date of May 28, 2018.

Bron: Amgen

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pLADD Therapy Found to Induce Both Innate and Adaptive Immunity

Aduro Biotech presented preliminary observations from a case study of a patient with metastatic colorectal cancer treated in Aduro’s ongoing Phase 1 study of its personalized neoantigen-based immunotherapy (pLADD). This Phase 1 proof-of-concept study is designed to evaluate the safety and tolerability of pLADD immunotherapy in adults with metastatic colorectal cancer that is microsatellite stable (MSS). Data were presented at the European Neoantigen Summit held in Amsterdam (April 24-26, 2018).

The immunological data presented demonstrated that neoantigens isolated and sequenced from the patient’s tissue samples, and engineered into a personalized immunotherapy, induced neoantigen-specific CD8+ T cells undetectable before pLADD treatment started. In addition to adaptive immunity, pLADD induced an innate response exemplified by gamma delta T cells, also thought to be important for successful immunotherapy. The patient’s neoantigens were selected using state-of-the-art algorithm identification technology developed by Aduro’scollaborator, Hanlee Ji, M.D., associate professor of medicine at the Stanford University School of Medicine.

“Although early, the immunological data obtained from this case study is encouraging, as it indicates that our pLADDimmunotherapy has the potential to induce a sustained, antigen-specific effect on the immune system,” said Andrea van Elsas, Ph.D., chief scientific officer of Aduro. “We believe our pLADD approach could offer a differentiated treatment option to patients with MSS colorectal cancer, who represent the vast majority of the colorectal cancer patient population and who have not been responsive to immune checkpoint inhibitors. In addition, these preliminary observations support our plan to combine pLADD with checkpoint inhibitors, which we believe could enhance the overall response in this patient setting. We look forward to reporting additional immunological data from this Phase 1 trial before the end of 2018.”

Preclinical data presented showed that mouse pLADD strains targeting tumor-specific neoepitopes induced a robust immune response, including induction of cytokines, chemokines, and antigen-specific CD8+ T cells.  In preclinical models of pLADD, remodeling of the tumor microenvironment with an increase in the CD8:Treg ratio was observed. The combination of pLADD with an anti-PD-1 antibody led to a sustained immune response and significantly improved efficacy in these mouse tumor models.

Bron: Aduro Biotech

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KH176 published in Scientific Reports

Khondrion, a leading clinical-stage pharmaceutical company focusing on small molecule therapeutics for mitochondrial diseases, announced the publication of a scientific article reporting on the development and unique mode of action of KH176, a clinical-stage drug candidate for the treatment of mitochondrial diseases. The work was carried out by the Khondrion R&D team in collaboration with Inoviem Scientific and the Radboud University Medical Center. The results were published in Scientific Reports.

KH176 is an orally bio-available small molecule in development by Khondrion for the treatment of mitochondrial (-related) diseases. The present study reports on the early development and selection of KH176 as Khondrion’s lead candidate and further explains its mode of action in primary cells obtained from mitochondrial patients.

“Elevated Reactive Oxygen Species (ROS) levels and a high sensitivity to redox-stress are two frequent cellular consequences in mitochondrial disease. Interestingly, we could demonstrate in several patient-derived cells that KH176 is an attractive candidate to correct both pathological phenotypes, illustrating its unique potential for this group of patients” says Dr. Julien Beyrath, Chief Operating Officer at Khondrion and first author of the study.

KH176 displays a dual mode of action, targeting both ROS and Redox disturbances. “Using cutting-edge target deconvolution technology, we could identify peroxiredoxin enzyme as the primary and novel target of KH176” added Dr. Beyrath. Research is ongoing to further unravel the exact molecular mechanism of interaction of KH176 with the peroxiredoxin enzyme, which will help the Khondrion R&D team to further improve their drug candidates. “The results presented highlight the potential of KH176 as a single molecule to be effective in a large group of heterogeneous mitochondrial diseases, but also other diseases with underlying ROS and Redox perturbations” adds Prof. dr. Jan Smeitink, CEO at Khondrion and last author of the study.

Bron: Khondrion

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Europa roept op tot actie voor een hogere vaccinatiegraad

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Het Europees Parlement riep afgelopen week de Europese Commissie en lidstaten op tot een actieplan voor een hogere vaccinatiegraad. Een fijne steun in de rug voor de World Health Organisation (WHO), die in het kader van de European Immunisation Week (23-29 april) ook extra aandacht vraagt voor het belang van vaccinatie. De week heeft als thema “vaccinatie als individueel recht en een gezamenlijke verantwoordelijkheid”. HollandBIO is helemaal in haar nopjes met de gemeenschappelijke boodschap: infectieziekten voorkomen is immers beter dan genezen!

In Nederland beschermen wij al sinds jaar en dag onze kinderen tegen nare infectieziekten via het Rijksvaccinatieprogramma. Maar dankzij nieuwe vaccinaties en vaccinatieschema’s kunnen we tegenwoordig veel meer mensen in verschillende levensfasen beschermen, van baby’s tot ouderen. HollandBIO vindt het daarom hoog tijd dat we in Nederland een nieuwe, levenslange vaccinatievisie en -strategie ontwikkelen. Wist je bijvoorbeeld dat vaccinatie…

Alleen als we de handen ineenslaan, maken we een kans in de strijd tegen infectieziekten. Samen met het Europees Parlement, de Europese Commissie en de WHO pleit HollandBIO daarom met hart en ziel voor de optimale inzet van vaccins in de strijd tegen infectieziekten.

Meer weten?

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Gezondere tomaten met CRISPR-Cas


Rijpe tomaten danken hun mooie rode kleur aan lycopeen. Het stofje geeft niet alleen kleur aan de tomaat, het is ook nog eens heel gezond. Lycopeen is namelijk een antioxidant en die beschermen onder meer tegen ziekten als kanker. Helaas moet je wel heel veel tomaten eten om dit gezondheidseffect te bewerkstelligen: de concentratie van lycopeen in een tomaat is erg laag. Onderzoekers van de China Agricultural University zijn er in geslaagd de concentratie maar liefst vijfmaal te verhogen. Dit hebben ze gedaan door met CRISPR-Cas verschillende genen, betrokken bij de omzetting van lycopeen in andere minder gezonde stoffen, uit te zetten. Hierdoor worden de tomaten niet alleen nog mooier rood, maar ook nog eens gezonder! En dat laatste is natuurlijk  wat we allemaal graag willen.

Bron: Frontiers in Plant Science

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New SPINRAZA Data Unveiled at AAN Annual Meeting

Biogen announced new findings detailing the benefits that SPINRAZA (nusinersen) demonstrates for both infantile- and later-onset spinal muscular atrophy (SMA) populations, including improvement in motor function as well as increased survival for the most severely affected. These findings are based on interim results from the SHINE open-label extension study and an analysis of SPINRAZA’s effects on mobility and fatigability in later-onset participants from the CS2/CS12 studies. The research will be presented at the American Academy of Neurology (AAN) Annual Meeting on April 21-27, 2018, in Los Angeles, California.

“These results reinforce SPINRAZA’s unprecedented and compelling efficacy across a broad range of SMA populations, enabling patients to improve mobility and motor function – and, for the most severely affected, increase their chances of survival,” said Alfred Sandrock, M.D., Ph.D., executive vice president and chief medical officer at Biogen. “We look forward to continuing to work with healthcare providers, institutions and SMA communities to provide access to SPINRAZA for those in need, no matter their age, disease severity or duration of the disease.”

The SHINE analysis reported interim results as of June 30, 2017, from the open-label extension study for patients (n=89) with infantile-onset SMA (most likely to develop Type 1) who transitioned from the Phase 3 ENDEAR study. Participants either initiated SPINRAZA treatment in ENDEAR and continued treatment through SHINE (n=65) or transitioned from the sham-control arm in ENDEAR to active treatment with SPINRAZA in SHINE (n=24).

“This analysis demonstrates that participants improved their motor function and increased event-free survival time, whether they initiated treatment earlier, as in ENDEAR and continuing in SHINE, or later, after receiving sham-control in ENDEAR and beginning treatment in SHINE,” said Diana Castro, M.D., lead study author, UT Southwestern Medical Center, Dallas, Texas. “It also confirms that those who initiated SPINRAZA treatment earlier saw greater motor milestone performance that continued to improve over time, and that no new safety concerns were identified.”

The interim results showed that participants who initiated SPINRAZA in ENDEAR and continued in SHINE, as well as those who received sham in ENDEAR and initiated SPINRAZA in SHINE, experienced improvements in HINE-2 motor milestones and general motor function as measured by CHOP INTEND. The median time to death or permanent ventilation for participants who initiated SPINRAZA in ENDEAR and continued in SHINE was 73 weeks. Among participants who received sham, the median time to death or permanent ventilation was 22.6 weeks within ENDEAR. The majority of subjects who were alive and did not require permanent ventilation after they received sham in ENDEAR remained event-free after receiving SPINRAZA in SHINE for a median time of 9.2 months.

An additional analysis – which was led by researchers at Columbia University Medical Center with support from Biogen – evaluated a subset of data from CS2 and CS12, two multicenter, open-label clinical trials, to assess the change in participants’ performance during the Six-Minute Walk Test (6MWT) and measures of fatigue. The analysis examined the walking ability and fatigability of ambulatory participants (n=14) ages two to 15 years with SMA Type 2 (n=1) or Type 3 (n=13) at study enrollment. Participants’ baseline median distance walked was 250.5 meters and baseline median fatigue level was 14.8 percent. Following SPINRAZA treatment, their walking distance increased (a median increase of 98 meters) while simultaneously, their fatigue level remained stable or decreased (a median decrease of 3.8 percent) over nearly 3 years.

“With SPINRAZA treatment, not only were participants able to walk longer distances but they experienced a stabilization or decrease in fatigue while doing so – both of which are meaningful, real-world benefits for individuals with SMA,” said Jacqueline Montes, P.T., Ed.D., N.C.S., Assistant Professor, lead study author, Columbia University Irving Medical Center, New York. “Furthermore, the analysis illustrates that SPINRAZA’s benefits continue to grow over time for Type 2 and 3 SMA populations.”

Bron: Biogen

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Nederlandse Q-koorts test scoort als beste in Australisch onderzoek

In Australië is onderzoek gedaan naar de effectiviteit van Q-koortstesten voorafgaand aan vaccinatie. Het Australian Rickettsial Reference Laboratory en Sullivan Nicolaides Pathology vergeleken verschillende testen met elkaar, waaronder Q-detect™. Deze test, ontwikkeld door het Nederlandse Innatoss, blijkt veruit de beste test voor screening op Q-koorts. De resultaten werden vandaag gepresenteerd tijdens het Europese ECCMID congres in Madrid.

Het vaccineren van werknemers die een hoger risico op Q-koorts lopen is in Australië verplicht. Het vaccin dat hiervoor gebruikt wordt kan echter bijwerkingen geven bij mensen die al eerder zijn blootgesteld aan de Q-koortsbacterie. Deze mensen mogen niet gevaccineerd worden. Om hen uit te sluiten, wordt een screening uitgevoerd. Hiervoor moet een antistoftest gedaan worden, en als die negatief is een huidtest.

In het Australische vaccinatie-onderzoek onder leiding van Q-koortsexpert Dr. Stephen Graves werden verschillende Q-koortstesten vergeleken. De Nederlandse Q-detect test, die tijdens de Nederlandse Q-koortsepidemie werd uitgevonden door het RadboudUMC, werd voor het eerst in een dergelijk onderzoek meegenomen.

Nederlandse Q-detect test blijkt veruit de beste

De resultaten spreken voor zich. Van alle testen in het onderzoek is Q-detect de enige die het predicaat “goede test” krijgt. Het is de enige test in het onderzoek die alle 8 personen die eerder aan de Q-koortsbacterie werden blootgesteld, wist te identificeren.

Buitengewoon verrassend zijn de resultaten van de testen die op dit moment worden gebruikt voor screening.. Zo vindt men met de huidtest slechts 3 van de 8 personen. Zelfs in combinatie met de hoogst aangeschreven antistoftest, de IFA test, werden niet alle personen gevonden.

“Q-detect is niet alleen de meest gevoelige test in ons onderzoek, maar de test is ook de veel minder ingrijpend en makkelijker inzetbaar in Australië dan de huid- en antistoftest die op dit moment gebruikt worden,” aldus Dr. Graves.

Nederlandse overheid aan zet

Op dit moment is alleen in Australië het menselijke Q-koortsvaccin beschikbaar. In Nederland dus nog niet. Barbara Schimmer, onderzoeker bij het RIVM, adviseerde vorige week bij de verdediging van haar proefschrift om vaccinatie serieus te overwegen bij beroepsgroepen met een hoog risico op Q-koorts.

Anja Garritsen, directeur van Innatoss, ziet mogelijkheden voor de Nederland om voorop te lopen: “Er wordt in Europa nog niet gevaccineerd tegen Q-koorts. Het Australische vaccin wordt echter al heel lang succesvol ingezet. Het RIVM heeft ook al laten zien dat de bijwerkingen bij een goede screening vooraf beperkt zijn. Hopelijk gaat de Nederlandse overheid op korte termijn een vaccinatie-proef starten waarbij gescreend wordt met de nieuwe Q-detect test. Zo kan de Q-koortsvaccinatie op een zo eenvoudig en effectief mogelijke manier ingevoerd worden ten behoeve van deze beroepsgroep”.

Q-detect is niet de enige Q-koorts gerelateerde innovatie van Innatoss. Het bedrijf uit Oss werkt ook mee aan de ontwikkeling van een nieuw Q-koortsvaccin, zonder de nare bijwerkingen die het Australische vaccin kan hebben. Dit project wordt gefinancierd door het Amerikaanse ministerie van Defensie.

De originele presentatie als wetenschappelijke poster op ECCMID 2018 is hier te vinden

Bron: q-koorts.nl

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Anergis and Mymetics Start Research Collaboration Project

Mymetics Corporation, a pioneer and leader in the research and development of virosome-based vaccines, and Anergis SA, a company developing Contiguous Overlapping Peptides (COPs) for ultra-fast allergy immunotherapy, announced that Mymetics SA, the Swiss subsidiary of Mymetics Corporation and Anergis SA have entered into a Research Collaboration project.

The pre-clinical study program will evaluate the immunogenicity profile of the Anergis peptides designed to treat birch allergy (the Bet v1 COPs) when presented on Mymetics’ proprietary virosomes, with or without undisclosed TLR ligands or other adjuvants, and will compare the results to Anergis’ AllerT product combination (Bet v1 COPs with aluminum hydroxide).

The research collaboration will start now and the results are expected by Q1 2019. If this project is successful, Anergis will have the option to enter into an exclusive license agreement for the use of virosomes in allergy.

“We are very excited to start this initial research project with Anergis, a leading company in ultra-fast allergy immunotherapy” said Ronald Kempers, CEO of Mymetics. “We look forward to show that our proprietary virosome technology and vaccine expertise can make a valuable difference in improving the effectiveness of treating allergies.”

“On the basis of the extensive clinical experience available with virosomes and with Anergis COPs against birch allergy, we are convinced that their combination represents a highly attractive opportunity to develop safe and efficacious ultra-fast COP allergy vaccines” commented Vincent Charlon, CEO of Anergis.

Bron: Mymetics

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MDxHealth: SelectMDx Included in Dutch DRG Reimbursement System

MDxHealth SA, a world leader in molecular diagnostics for urological cancers, announced the inclusion of SelectMDx for Prostate Cancer, its non-invasive ‘liquid biopsy’ test that helps to identify patients at increased risk of having aggressive prostate cancer, in the Dutch Diagnosis Related Groups (DRG) reimbursement system.

The DRG reimbursement system was introduced in the Netherlands in 2005. It specifies the reimbursable amounts for 30,000 different treatments and is regulated by the Dutch Healthcare Authority (NZA). Diagnosing and treatment of prostate cancer are also reimbursed under the DRG-system. The SelectMDx test may be used under the DRG-system. Reimbursement amounts are directly negotiated between the healthcare insurers and the healthcare providers. Several Dutch hospitals have already incorporated the SelectMDx test in their prostate cancer diagnostic workflow.

Dr. Jan Groen, Chief Executive Officer of MDxHealth, commented: “This is a positive development for MDxHealth and serves as an important step in our strategy to increase the adoption and acceptance of our SelectMDx CE marked test in Europe among urologists and payors. We believe that in light of the ageing male population in the US and Europe, the use of SelectMDx in active monitoring and primary care settings could quadruple the market opportunity for SelectMDx in the mid-term to more than 4 million patients annually in the US and Europe. With the EAU guidelines inclusion for SelectMDx announced last month, we look forward to providing further updates on our progress in European markets.”

Bron: MDxHealth

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InteRNA Demonstrates Preclinical Proof-of-Concept

InteRNA Technologies presented proof-of concept data on lead microRNA candidate INT-1B3 highlighting its distinct mode of action that combines antitumor activity, modulation of the immunosuppressive tumor microenvironment and long-term immunity against cancer. INT-1B3 is a lipid nanoparticle (LNP) formulated, chemically modified microRNA 193a-3p mimic that can be delivered systemically to cancer cells. MicroRNAs are naturally occurring small RNA interfering molecules which represent a part of the body’s arsenal to regulate gene expression, each targeting a specific set of genes. MicroRNA 193a-3p is a known tumor suppressor microRNA that is downregulated in many cancers and the reintroduction of the synthetic mimic aims to restore its function and generate biological responses relevant to key hallmarks of cancer. The results were presented in a poster at the American Association for Cancer Research (AACR) Annual Meeting, held in Chicago, IL, from April 14-18, 2018.

“Overall these data strongly support the unique potential of microRNAs, and INT-1B3 in specific, as a novel therapeutic modality in cancer that acts as a ‘combination treatment in one drug’. It is an important milestone for InteRNA because it validates our microRNA platform and demonstrates the focus and commitment of the team over the last years,” said Dr. Roel Schaapveld, CEO of InteRNA. “Our lead candidate stands out through a unique mode of action and an advanced delivery technology to achieve effective tumor tissue delivery. We are preparing to move this exciting program towards clinical assessment.”

The study investigated multiple biological effects as well as the underlying mechanism of action of INT-1B3 in both tumor cell-based assays and experimental tumor models. The data show that INT-1B3 specifically targets pivotal oncogenes including MCL1, CCND1 and KRAS to induce cell death and apoptosis. In addition, it targets ENTPD1 (CD39) and NT5E (CD73), two crucial enzymes in the ATP to adenosine degradation pathway which has been linked to evasion of tumor immune surveillance. Importantly, INT-1B3 showed a good safety and tolerability profile in all animal studies with no treatment-related adverse events.

The most striking results were observed in a syngeneic mouse model of triple negative breast cancer (TNBC 4T1) in which INT-1B3-treated animals survived significantly longer than control or anti-PD-1 treated mice. The INT-1B3-treated mice showed a significant modulation of the immunosuppressive tumor microenvironment, illustrated by an increase in T cell function and a subsequent increase in cytotoxic T-cell frequency. In addition, the number of immunosuppressive regulatory T cells decreased, indicating a transition from an immunosuppressive to an immune stimulatory tumor microenvironment. To investigate the long-term immunity potential, the surviving INT-1B3-treated mice were challenged with the same tumor cells (4T1) and followed up for 28 days in the absence of any further treatment. Although three of the eight mice showed an initial tumor take and growth, a rapid and complete tumor regression with 100% of the animals being tumor-free was achieved by the completion of the study, suggesting a long-term immunization against the 4T1 cancer cells. The same mice were then re-challenged with mouse liver cancer cells (H22) to investigate the long-term immunity potential against an unrelated cancer cell type. Despite an initial and efficient (100%) tumor take in all mice, complete tumor regression was seen within the 28-day follow-up period providing an indication that INT-1B3 can induce a long-term broad cancer immunity. Furthermore, INT-1B3 demonstrated pronounced tumor growth inhibition in human xenograft melanoma and liver cancer models.

The poster, titled “Pharmacologic profile of INT-1B3: a novel synthetic microRNA 193a-3p mimic for therapeutic intervention in oncology” was presented by InteRNA’s Senior Research Scientist, Dr. Sanaz Yahyanejad and Chief Development Officer, Dr. Michel Janicot and is available on InteRNA’s website through the following link: https://interna-technologies.com/technology/scientific-publications/.

Bron: InteRNA technologies