BerGenBio will be hosting a live webcast and Q&A session at 10.00 CEST, May 18
BERGEN, Norway, May 18, 2021: BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical need, provides top-line data from BGBC020, a randomized Phase II clinical study evaluating the efficacy and safety of bemcentinib in hospitalized COVID-19 patients.
BGBC020:
BGBC020 was conducted from October 2020 across multiple sites in South Africa and India. With 115 patients enrolled at the end of March 2021.
So, the baseline demographics were balanced between groups; 60 patients enrolled in India and 55 in South Africa. The median age of enrolled patients was 54.0 years (range 19 – 89y), with 34% being female. The vast majority of patients were WHO OCS grade 4 at baseline, 93 of 115 (83%), with 11 enrolled in each grade 3 and grade 5 cohorts. Hence, the most common co-morbidities were diabetes (27%), cancer (8%), and heart disease (7%).
The patients were randomized to receive standard of care (SOC) only or bemcentinib with SOC; 76% of patients received steroids, and 51% also received redeliver. As part of their therapy. Patients were closely evaluated through 29 days following admission to assess efficacy endpoints. And to 90 days after randomization to determine longer outcomes.
A post-doc analysis (not specified in the protocol) identified a sub-group of patients. With higher baseline severity (Grade 4 & 5) and C-Reactive Protein (CRP) >30mg/L, representing more than 50% of the patients in the study. This sub-group showed encouraging evidence of a more substantial treatment effect by bemcentinib across all endpoints evaluated. C-reactive protein (CRP) is an established biomarker, widely used in clinical practice to detect acute inflammation, rising within the first few hours of the acute phase response. In COVID-19, the rising level of CRP in the bloodstream correlates with increasing disease severity.
Patients well-tolerated Bemcentinib, and no safety signals of concern were identified.
Ventilator Free Survival
Ventilator Free Survival is defined as the proportion of patients that survived to day 29. Without admission to ICU and the need for ventilator-assisted breathing. Patients treated with bemcentinib appeared to be protected from an early deterioration at day 2 or 3, compared to patients treated with SOC. With this effect being maintained through 29 days. In the sub-group of patients with increased disease severity. Ventilator-free survival was higher (90%) with bemcentinib treatment compared to SOC on its own (72%).
Primary endpoint
So, the primary endpoint (time to improvement by two WHO grades, from baseline, or time to discharge or fitness for discharge). Marginally favored bemcentinib treatment over SOC, but the difference was not statistically significant. This endpoint is subject to a broad range of subjective factors, including variation in clinician practice, local epidemic case rates, ensuing demand for bed occupancy in hospitals, and resource availability. Therefore, this endpoint may not directly measure the individual patient’s health or the benefit from bemcentinib.
Overall Survival
So, the Analysis of overall survival in the BGBC020 study was combined with the ACCORD2 study. It is conducted in the UK with an analogous phase 2 design. The ACCORD2 platform study recommended enrollment in the UK winter wave of the local epidemic, enrolling patients between December 2020 and March 2021 (30 to the bemcentinib arm in both phases of the study is with 32 eligibility-matched control patients).
Mortality rates in ACCORD2 SOC treated patients were higher than those in BGBC020 at day 29; (5 of 32 patients (16%) in ACCORD2, versus 3 of 57 (5%) in BGBC020.
Overall in the combined studies, survival to day 29 was 96.5% (83 of 86 evaluable patients). In bemcentinib arm versus 91.0% (81 of 89) treated with SOC alone.
Anti-Viral mechanism of action
The evaluation of patients’ viral load while hospitalized was an exploratory endpoint in the study. With bemcentinib treatment being associated with a shorter apparent time. To SARS-CoV2 not being detected in fluid body samples, than in those treated with SOC alone.
Next steps
Full scientific Analysis of BGBC020 will be combined with the ACCORD2. Data set in a meta-analysis for Presentation at a scientific conference and publication in a peer-reviewed journal.
So, the totality of data informs a benefit from bemcentinib in treating a substantial subset of hospitalized COVID-19 patients. This will support ongoing engagement with regulatory agencies, government partners, and the industry.
Professor emeritus Stener Kvinnsland MD Ph.D., Director of BerGenBio and former Chair of Norwegian Korona Commission, commented:
“The greatest challenge faced by hospitals worldwide is an unmanageable demand for ICU capacity and ventilator support for COVID-19 patients. For the foreseeable future, despite recent progress with vaccinations. There remains a substantial global need for effective treatments for COVID-19 patients. That offers survival benefits and relief for intensive care demand in hospitals. The totality of data for bemcentinib is very encouraging in this respect and warrants further confirmation.”
Professor Tom Wilkinson MA Cantab MBBS Ph.D. FRCP FERS, Professor of Respiratory Medicine and Chief Investigator on the ACCORD program, commented:
So, “The COVID-19 pandemic persists, and there remains an urgent need for safe, convenient, and more effective treatment for a broad spectrum of patients. The novel mechanism of action of bemcentinib is independent of the SARS-CoV-2 spike protein and thus would be expected to retain its effect with the emergence of new, potentially vaccine-resistant, strains of the virus. The drug has a good safety profile and holds potential promise at this vital time.”
Richard Godfrey, Chief Executive Officer of BerGenBio, commented:
So, “The potential of bemcentinib to increase the rate of ventilator-free survival in more than 50% of hospitalized COVID-19 patients is very encouraging. This represents a meaningful outcome for both patients and healthcare systems and is of potentially great value. This real-world exploratory study was completed in several global geographies, with different demographics and ethnicities and evolving standards of care. Through diligent analysis of all the data collected, the totality of which supports the unique mechanism of action of bemcentinib in potentially treating hospitalized COVID-19 patients, we now have a clear clinical position for bemcentinib in this disease. We will continue our discussion of these results with the regulators, industry, and Government partners to determine the next steps.”
So, Presentation and webcast information.
BerGenBio will be hosting a live webcast and Q&A session at 10.00 CEST, May 18:
About AXL
So, AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases.
In COVID-19, AXL has two synergistic mechanisms of action, it acts as a co-receptor to ACE2, to which the spike protein of the SARS-CoV-2 virus attaches and enters the host cell, and AXL expression is upregulated in infected organs with an activation of the signaling pathway leading to suppression of the Type 1 Interferon immune response by infected cells and neighboring cells, in their environment. So, Pre-clinical research studies demonstrate that bemcentinib inhibits SARS-CoV-2 host cell entry and promotes anti-viral Type I interferon response.
In cancer, an increase in AXL expression has been linked to critical mechanisms of drug resistance and immune escape by tumor cells, leading to aggressive metastatic cancers. AXL suppresses the body’s immune response to tumors and drives treatment failure across many cancers. High AXL expression defines a very poor prognosis subgroup in most cancers. Therefore, AXL inhibitors, such as bemcentinib, have a potentially high value as monotherapy and as the cornerstone of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Hence, research has also shown that AXL mediates other aggressive diseases, including fibrosis.
About Bemcentinib
Bemcentinib (formerly known as BGB324) is a potential first-in-class, potent, and highly selective AXL inhibitor, currently in a broad phase II clinical development program. It is administered as an oral capsule and taken once per day. Ongoing clinical trials are investigating bemcentinib in COVID-19, and multiple solid and hematological tumors, combined with current and emerging therapies (including immunotherapies, targeted therapies, and chemotherapy) and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity.
About BerGenBio ASA
BerGenBio is a clinical-stage biopharmaceutical company focused on developing transformative drugs targeting AXL as a potential cornerstone of therapy for aggressive diseases, including immune-evasive, treatment-resistant cancers. The company’s proprietary lead candidate, bemcentinib, is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development program focused on the combination and single-agent therapy in cancer, leukemia, and COVID-19. A first-in-class functional blocking anti-AXL antibody, tilvestamab, is undergoing phase I clinical testing. In parallel, BerGenBio is developing a companion diagnostic test to identify patient populations most likely to benefit from AXL inhibition. So, This is also expected to facilitate more efficient registration trials supporting a precision medicine-based commercialization strategy.
So, BerGenBio is based in Bergen, Norway, with a subsidiary in Oxford, UK. The company is listed on the Oslo Stock Exchange (ticker: BGBIO).
Forward-looking statements
This announcement may contain forward-looking statements, which as such are not historical facts but are based upon various assumptions, many of which are based, in turn, upon further assumptions. These assumptions are inherently subject to significant known and unknown risks, uncertainties, and other essential factors. Therefore, such risks, uncertainties, contingencies, and other important factors could cause actual events to differ materially from the expectations expressed or implied in this announcement by such forward-looking statements.
This news was shared to Prittle Prattle News via press release.
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