AM-Pharma B.V., an emerging leader focused on the treatment of kidney disease, sepsis and organ injury, today announced that the first patients with COVID-19 infection and sepsis-associated acute kidney injury (SA-AKI) have been enrolled in the Company’s Phase III REVIVAL pivotal trial in an exploratory cohort to assess the safety, tolerability and clinical benefit of recombinant alkaline phosphatase.

Patients with severe COVID-19 infection often present with acute severe inflammation and organ failure. Recent studies conducted in the US demonstrated that up to 90% of the COVID-19 patients that received mechanical ventilation also suffered from AKI and that the development of AKI in these patients is associated with poor prognosis.¹ AM-Pharma received an innovation credit of up to EUR 5 million from the “Netherlands Enterprise Agency” (RVO.nl), which has been established by the Dutch Ministry of Economic Affairs and Climate Policy to support the development of innovative programs with promising market potential.

“The ongoing coronavirus pandemic and the lack of treatment options for severe cases has been devastating for patients, their families and medical communities around the world,” commented Erik van den Berg, Chief Executive Officer at AM-Pharma. “The prevalence of COVID-19 infections and the high AKI comorbidity support our decision to include this additional cohort into our Phase III REVIVAL pivotal study. By providing our proprietary recombinant alkaline phosphatase to clinicians for evaluation in severe COVID-19 cases, we aim to make our novel treatment option available for these patients.”

The REVIVAL Phase III pivotal trial is a randomized, double-blind, placebo-controlled, two-arm, parallel-group, multi-center trial to evaluate the efficacy and safety of AM-Pharma’s proprietary human recombinant alkaline phosphatase for the treatment of patients with SA-AKI. The study will enroll approximately 1400 patients with SA-AKI in the main study population. In two exploratory cohorts, up to 100 patients with moderate Chronic Kidney Disease (CKD) and up to 100 patients with COVID-19 will be enrolled. The primary aim of the study is to confirm the improvement on the primary endpoint of 28-day all-cause mortality, as observed in the Phase II STOP-AKI study. Secondary endpoints include the treatment effect on long-term Major Adverse Kidney Events (MAKE), on the use of organ support, length of stay in the ICU and on 90-day all-cause mortality. Further information on this study can be found at www.clinicaltrials.gov, NCT04411472 (REVIVAL).

“We have seen the potential of AM-Pharma’s proprietary recombinant human alkaline phosphatase to benefit patients with sepsis and acute kidney injury, as demonstrated in the Phase II STOP-AKI study,” said John A. Kellum, M.D., Professor, Vice Chair Department of Critical Care Medicine and Director at the Center for Critical Care Nephrology at University of Pittsburgh. “This is very relevant for severe COVID-19 patients as many of these patients also experience AKI, with increased AKI severity being correlated with increased mortality.”

Professor Peter Pickkers, M.D., Ph.D., Chair of Experimental Intensive Care Medicine, Radboud University Medical Center, and principal investigator of the REVIVAL study added: “The relative reduction in mortality of 40% and significant improvement in renal function over the course of the Phase II STOP-AKI study period support the hypothesis that AM-Pharma’s drug candidate might provide a unique treatment opportunity for severe COVID-19 patients with acute kidney injury. I am excited to continue our collaboration with AM-Pharma for this trial.”

For the Phase III REVIVAL trial, potentially over 100 sites across Europe and North America are actively recruiting patients with SA-AKI in the trial. Enrollment completion of the first 400 patients in the main study population is expected by the end of 2021. The company expects to complete target enrollment and to announce data on the primary endpoint of 28-day all-cause mortality in 2023.

Source: AM-Pharma (Press release)

Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, and its research alliance partners Fondazione Telethon and Ospedale San Raffaele, announced that the European Commission (EC) granted full (standard) market authorization for Libmeldy (autologous CD34+ cells encoding the ARSA gene), a lentiviral vector-based gene therapy approved for the treatment of metachromatic leukodystrophy (MLD), characterized by biallelic mutations in the ARSA gene leading to a reduction of the ARSA enzymatic activity in children with i) late infantile or early juvenile forms, without clinical manifestations of the disease, or ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline. Libmeldy is the first therapy approved for eligible patients with early-onset MLD.

MLD is a very rare, fatal genetic disorder caused by mutations in the ARSA gene which lead to neurological damage and developmental regression. In its most severe and common forms, young children rapidly lose the ability to walk, talk and interact with the world around them, and most pass away before adolescence. Libmeldy is designed as a one-time therapy that aims to correct the underlying genetic cause of MLD, offering eligible young patients the potential for long-term positive effects on cognitive development and maintenance of motor function at ages at which untreated patients show severe motor and cognitive impairments.

“Today’s EC approval of Libmeldy opens up tremendous new possibilities for eligible MLD children faced with this devastating disease where previously no approved treatment options existed,” said Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard. “Libmeldy is Orchard’s first product approval as a company, and I am extremely proud of the entire team who helped achieve this milestone. We are grateful for and humbled by the opportunity to bring this remarkable innovation to young eligible patients in the EU.”

With Libmeldy, a patient’s own hematopoietic stem cells (HSCs) are selected, and functional copies of the ARSA gene are inserted into the genome of the HSCs using a self-inactivating (SIN) lentiviral vector before these genetically modified cells are infused back into the patient. The ability of the gene-corrected HSCs to migrate across the blood-brain barrier into the brain, engraft, and express the functional enzyme has the potential to persistently correct the underlying disease with a single treatment.

“The EC approval of Libmeldy comes more than a decade after the first patient was treated in clinical trials performed at our Institute, and ushers in a remarkable and long-awaited shift in the treatment landscape for eligible MLD patients, said Luigi Naldini, M.D, Ph.D., director of the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy. “Our team at SR-Tiget has been instrumental in advancing the discovery and early-stage research of this potentially transformative therapy to clinical trials in support of its registration through more than 15 years of studies supported by Fondazione Telethon and Ospedale San Raffaele, and we are extremely proud of this achievement and what it means for patients and the field of HSC gene therapy.”

“MLD is a heart-breaking disease that causes immeasurable suffering and robs children of the chance of life,” said Georgina Morton, chairperson of ArchAngel MLD Trust. “As a community, we have been desperate for a treatment for young MLD patients, and we are incredibly excited to now have such a ground-breaking option approved in the EU.”

The marketing authorization for Libmeldy is valid in all 27 member states of the EU as well as the UK, Iceland, Liechtenstein and Norway. Orchard is currently undertaking EU launch preparations related to commercial drug manufacturing, treatment site qualification and market access.

Data Supporting the Clinical and Safety Profile of Libmeldy

The marketing authorization for Libmeldy is supported by clinical studies in both pre- and early- symptomatic, early-onset MLD patients performed at the SR-Tiget. Early-onset MLD encompasses the disease variants often referred to as late infantile (LI) and early juvenile (EJ). Clinical efficacy was based on the integrated data analysis from 29 patients with early-onset MLD who were treated with Libmeldy prepared as a fresh (non-cryopreserved) formulation. Results of this analysis indicate that a single-dose intravenous administration of Libmeldy is effective in modifying the disease course of early-onset MLD in most patients.

Clinical safety was evaluated in 35 patients with MLD (the 29 patients from the integrated efficacy analysis as well as six additional patients treated with the cryopreserved formulation of Libmeldy). Safety data indicate that Libmeldy was generally well-tolerated. The most common adverse reaction attributed to treatment with Libmeldy was the occurrence of anti-ARSA antibodies (AAA) reported in five out of 35 patients. Antibody titers in all five patients were generally low and no negative effects were observed in post-treatment ARSA activity in the peripheral blood or bone marrow cellular subpopulations, nor in the ARSA activity within the cerebrospinal fluid. In addition to the risks associated with the gene therapy, treatment with Libmeldy is preceded by other medical interventions, namely bone marrow harvest or peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies, the safety profiles of these interventions were consistent with their known safety and tolerability.

Source: Orchard Therapeutics (Press release)

Afgelopen week publiceerde Tweede Kamerlid Hayke Veldman (VVD) een initiatiefnota, een voorstel voor beleid, waarin hij pleit voor grotere investeringen in infectiepreventie. De huidige COVID-19 pandemie vormt daarin een ultiem voorbeeld van de gevolgen van een uitbraak voor gezondheid, economie en welzijn. Veldman stelt dat anticiperen op volgende infectieziekten cruciaal is. We moeten tot beleid komen dat diverse onzekerheden wegneemt in de ontwikkeling en beschikbaarheid van vaccins, antibiotica en andere behandelingen. HollandBIO ziet de Initiatiefnota als kans om het Nederlandse infectieziektenbeleid verder te versterken, en doet er het liefste nog een schepje bovenop.

De initiatiefnota stelt verbeteringen voor op vier gebieden: rond onderzoek en ontwikkeling van innovaties als vaccins en antibiotica, de beoordeling van vaccins, de beschikbaarheid van vaccins en de implementatie. De rode draad is dat Nederland, op nationaal en Europees niveau, meer werk moet maken van toekomstscenario’s en een investeringsperspectief op preventieve interventies. HollandBIO sluit zich hier volledig bij aan, en ziet de nota als opmaat naar een toekomstig Deltaplan Infectieziekten waarin naast vaccinaties en antibiotica ook andere cruciale middelen, zoals antivirale middelen en een goede infectieziektediagnostiek, een plek krijgen.

Benieuwd naar de hele Initiatiefnota? Lees dan hier verder.

Lees ook de bijdrage van Annemiek Verkamman aan de campagne Infectieziekten.

Glycostem Therapeutics B.V., a leading clinical-stage company focused on the development of therapeutic off-the-shelf Natural Killer (NK) cells, today announced that the first patient has been dosed in its pivotal phase I/IIa trial of oNKord^® for the treatment of Acute Myeloid Leukemia (AML). The WiNK trial will enroll 33 AML patients at eight clinical sites based in five European countries. oNKord^® is the company’s first-generation off-the-shelf allogeneic NK cellular immunotherapy product. Glycostem is furthermore developing a range of second (CAR-NK) and third generation (TCR-NK) NK products in-house.

“We are thrilled about the first patient being dosed in this pivotal trial. This important milestone potentially paves the way for a positive impact on the lives of patients with AML who are at high risk of relapse. The preliminary efficacy data obtained with oNKord^® is very promising and we are looking forward to the data from this study, which will allow us to draw conclusions regarding oNKord^® safety and tolerability and most importantly its efficacy for treatment of AML patients,” tells Troels Jordansen, CEO at Glycostem.

“We are very excited about being involved in the WiNK trial and to learn what the efficacy of oNKord^® will be on eradicating measurable residual disease (MRD) in AML patients,” tells Professor Heuser, Investigator and Head of the central laboratory for MRD assessment at the Hannover Medical School in Germany. “Currently, two thirds of MRD-positive AML patients who are in complete morphologic remission will relapse, and unfortunately, there is no cure for this group of patients if allogeneic stem cell transplantation is not an option. Therefore, the outcome of this trial is literally of vital importance and positive results could have a very significant impact on the prospects of current and future patients we are treating.”

Evaluating safety, tolerability and efficacy                       

WiNK (ClinicalTrials.gov identifier: NCT04632316) is a prospective two-stage, open-label, single arm, multicenter phase I/IIa trial to evaluate the safety and efficacy of oNKord^®, an off-the-shelf, ex vivo-cultured allogeneic NK cell preparation, in 33 adults with AML who are in complete morphologic remission with residual measurable disease and with no strong indication for hematopoietic stem cell transplantation.

Stage A of the trial is designed to assess the safety and tolerability of escalating doses of oNKord^® in three cohorts of three subjects each. An Independent Data Monitoring Committee (IDMC) will review safety data of all treated subjects in each cohort and make recommendations before moving to the next dose. Stage B of the trial will enroll an additional 24 subjects to evaluate the safety, tolerability and efficacy of oNKord^® at the recommended phase II dose, as identified from stage A.

Source: Glycostem (Press release)