Update on Siltuximab Clinical Study

RNS Number : 5022I

Ergomed plc

02 April 2020

 

RNS REACH

PRESS RELEASE

Update on Siltuximab Clinical Study: Interim Analysis Data for Siltuximab-Treated COVID-19 Patients

Guildford, UK - 2 April 2020: Ergomed plc (LSE: ERGO) ('Ergomed' or the 'Company'), a company focused on providing specialised services to the pharmaceutical industry, notes the recent update provided by EUSA Pharma (EUSA) concerning the study of siltuximab, an interleukin (IL)-6 targeted monoclonal antibody, for the treatment of patients with COVID-19 who have developed serious respiratory complications (Siltuximab In SeriousCOVID-19; SISCO Study). Yesterday EUSA announced initial preliminary findings from the SISCO Study, based on a pre-planned data analysis on 24 March 2020.

As previously announced the study is sponsored by the Papa Giovanni XXIII Hospital in Bergamo, Italy and supported by EUSA. Ergomed is providing clinical development and research services for the study and has been integrally involved in the design and implementation of the study from a clinical and operational perspective. See details of full announcement below.

Dr Miroslav Reljanović, Executive Chairman of Ergomed, said: "We are pleased to see the preliminary data which will help inform the most appropriate use of siltuximab in patients with COVID-19 suffering from serious respiratory complications. We continue to provide clinical development and research services, working closely with the investigators at the Papa Giovanni XXIII Hospital and with EUSA. We look forward to the completion of the study and the insights it might bring for the development of a treatment for COVID-19."

The full text of the announcement issued by EUSA on 1 April is as follows:

EUSA Pharma and Papa Giovanni XXIII Hospital, Italy, Provide Interim Analysis Data for Siltuximab-Treated COVID-19 Patients from the SISCO Study

HEMEL HEMPSTEAD, United Kingdom & BERGAMO, Italy - 1^st April 2020 - EUSA Pharma, a global biopharmaceutical company focused on oncology and rare disease, today announced initial preliminary findings from the Papa Giovanni XXIII Hospital sponsored SISCO (Siltuximab In Serious COVID-19) Study,¹ based on a pre-planned data analysis on 24 March 2020.

Siltuximab is an interleukin (IL)-6 targeted monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as well as in a number of other jurisdictions worldwide for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative (also known as idiopathic MCD; iMCD). Siltuximab is under investigation for COVID-19 patients who have developed serious respiratory complications, the leading cause of morbidity and mortality.

The interim data, presented from the first 21 patients treated with siltuximab and followed for up to 7 days, show that one-third (33%, n=7) of patients experienced a clinical improvement with a reduced need for oxygen support and 43% (n=9) of patients saw their condition stabilise, indicated by no clinically relevant changes. Combined, this means that over three-quarters of patients treated with siltuximab (76%, n=16) had either stable or improved disease at this interim analysis. A worsening of the disease was seen in 3 (14%) patients whilst 1 (5%) patient died and 1 (5%) experienced a cerebrovascular event.

Furthermore, C-Reactive Protein (CRP) levels, a marker of systemic inflammation, declined from baseline through to Day 5 following treatment with siltuximab in all patients with sufficient recorded values (100%, 16/16). This level of reduction was maintained in those patients (100%, 16/16) 7 days after receiving treatment with siltuximab. Reduction in CRP is considered a robust surrogate for indicating the efficacy of IL-6 inhibition.²

The majority (90%, 19/21) of patients presented with fever at baseline, 13/21 (62%) with a dry cough and 15/21 (71%) with dyspnoea (shortness of breath). Partial pressure of arterial oxygen (PaO₂) to percentage of inspired oxygen (FiO₂), otherwise known as the P/F ratio or lung function, and IL-6 had out of normal ranges at baseline in the majority of patients with a median P/F ratio of 127 (excluding those >300 and indicating Acute Respiratory Distress Syndrome [ARDS]³) and median peripheral IL-6 levels of 140 pg/mL (range 113-239 pg/mL). Serum CRP was elevated in all patients at baseline with a median of 23 mg/dL (range 10-43 mg/dL).

A manuscript is in preparation for submission to a leading medical journal, and the pre-print summary has been deposited and will be available via  medRxiv.org  imminently.

Professor Alessandro Rambaldi, MD, PhD, Papa Giovanni XXIII Hospital, Bergamo, Italy, Study Sponsor-Investigator and Director of the Hematology Unit and Department of Oncology and Hematology , said: "The team at Papa Giovanni XXIII Hospital are pleased to share these preliminary observational data. Whilst we are yet to identify and analyse the control group of patients, these initial data in siltuximab-treated patients provide vital information to guide decisions regarding appropriate use of siltuximab in both the real-world and new COVID-19 studies as we continue to investigate the role IL-6 blockade can play. Importantly, these preliminary uncontrolled data confirm high levels of IL-6 at baseline, with baseline CRP also high but declining with siltuximab treatment, suggesting a role for monoclonal antibodies as a possible therapeutic strategy for this fatal infectious disease. Further data will be made available on remaining patients, the case-control analysis and 30 day follow-up of mortality as they become available."

Lee Morley , Chief Executive Officer, EUSA Pharma, said: "We are very pleased to be able to release these preliminary data from the SISCO Study and hope the findings will help to guide real-world treatment decisions during this critical emergency situation. We look forward to engaging in further studies to research the potential of siltuximab for patients suffering severely with respiratory complications from COVID-19 and making additional data available as soon as possible. We are very grateful to the team at Papa Giovanni XXIII Hospital in Bergamo, Italy, for their extraordinary efforts to undertake the SISCO Study and collate these interim data under extremely difficult circumstances."

About the SISCO Study

Sponsored by the Papa Giovanni XXIII Hospital, the SISCO Study is an observational case-control trial of siltuximab, a chimeric monoclonal antibody targeting human IL-6, for the treatment of COVID-19 patients who develop serious respiratory complications. Ergomed plc (LSE: ERGO), a company focused on providing specialised services to the pharmaceutical industry, is providing clinical research services for the study.

The study represents the data collection and analysis of a series of patients treated under an ongoing emergency compassionate use protocol. The study is investigating two cohorts retrospectively, hospitalised patients prior to admission to an intensive care unit (ICU) or patients already requiring intensive care, and will compare to matched controls. Primary endpoints are reduction in the need of invasive ventilation, time spent in ICU or 30-day mortality.

Emerging evidence suggests that some patients with COVID-19 may respond with overproduction of IL-6, an inflammatory cytokine, leading to a cytokine storm - when the immune system becomes over-stimulated and attacks the patient's own body. Elevated IL-6 levels are associated with severity of disease and can lead to serious lung complications and/or Acute Respiratory Distress Syndrome (ARDS) - the leading cause of mortality in patients with COVID-19. Therefore, direct targeting of this cytokine may improve clinical outcomes in these critically ill patients.

The SISCO study has enrolled a total of 25 patients with confirmed SARS-CoV-2 infection (COVID-19) and respiratory complications of which preliminary data is presented from the first 21 treated with siltuximab. All patients in the study were treated with siltuximab at a dose of 11mg/kg infused over 1 hour with a second dose possible at physician discretion. Of the 21 patients treated with siltuximab, 5 received a second dose (5/21; 24%) 48-72 hours following the initial infusion.The majority of patients were male (18/21, 86%) with ages ranging from 48 to 75 years. The most prevalent comorbidities in this group of patients were: hypertension in 43% (9/21), cardiovascular disease in 19% (4/21), diabetes in 24% (5/21) of patients, respectively.

This study will provide important data to inform future clinical studies, discussions on which are ongoing, to further investigate the efficacy of siltuximab in patients with COVID-19 who develop serious respiratory complications. Initial data have been announced today. The next phase of data, which will compare outcomes in matched case-control patients not treated with siltuximab, is expected in the coming weeks.

References

1 SISCO Study (NCT04322188);  https://www.clinicaltrials.gov/ct2/show/NCT04322188

2 Clin Cancer Res; 21(6) March 15, 2015  https://clincancerres.aacrjournals.org/content/21/6/1248.long

3 JAMA, 307 (23), 2526-33 2012:  https://jamanetwork.com/journals/jama/article-abstract/1160659

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About siltuximab

Siltuximab is a monoclonal antibody that blocks the action of interleukin (IL)-6, a multifunctional cytokine detected at elevated levels in multiple inflammatory conditions.

It is approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as well as in a number of other jurisdictions worldwide, under the brand name SYLVANT^®, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative (also known as idiopathic MCD; iMCD). iMCD is a rare, life-threatening and debilitating lymphoproliferative disorder, which causes abnormal overgrowth of immune cells and shares many symptomatic and histological features with lymphoma.

Siltuximab is not approved for the treatment of COVID-19.

EUSA Pharma has exclusive rights to SYLVANT^® globally. EUSA Pharma has granted BeiGene, Ltd., exclusive development and commercialisation rights to SYLVANT^® in Greater China.

Indications and Usage of SYLVANT^® -  See full Prescribing Information for additional information .

SYLVANT^® (siltuximab) is indicated for the treatment of patients with multicentric Castleman disease (MCD) who are HIV negative and HHV-8 negative.

Limitations of Use: SYLVANT^® was not studied in patients with MCD who are HIV positive or HHV-8 positive because SYLVANT^® did not bind to virally produced IL-6 in a nonclinical study.

Contraindications : Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT^®.

Dosage and Administration

Administer SYLVANT^® 11 mg/kg over 1 hour as an intravenous infusion every 3 weeks until failure.

Perform hematology laboratory tests prior to each dose of SYLVANT^® therapy for the first 12 months and every 3 dosing cycles thereafter. If treatment criteria outlined in the Prescribing Information are not met, consider delaying treatment with SYLVANT^®. Do not reduce dose.

Do not administer SYLVANT^® to patients with severe infections until the infection resolves.

Discontinue SYLVANT^® in patients with severe infusion related reactions, anaphylaxis, severe allergic reactions, or cytokine release syndromes. Do not reinstitute treatment.

About EUSA Pharma

Founded in March 2015, EUSA Pharma is a world-class biopharmaceutical company focused on oncology and rare disease. The company has extensive commercial operations in the United States and Europe, alongside a direct presence in select other markets across the globe. EUSA Pharma is led by an experienced management team with a strong record of building successful pharmaceutical companies, and is supported by significant funding raised from leading life science investor EW Healthcare Partners. For more information please visit:  www.eusapharma.com .

About Papa Giovanni XXIII Hospital

Papa Giovanni XXIII Hospital is one of the biggest hospitals in Lombardy, covering 320 thousand square meters in total and comprising more than 900 beds. Among the areas of excellence, an important role is covered by the Cancer Center that brings patients from the whole national territory and also from foreign countries. The Hospital is playing a leading role in the Italian response to the ongoing global COVID-19 pandemic.

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Enquiries:

Ergomed plc	Tel: [phone]
Miroslav Reljanović (Executive Chairman)
Richard Barfield (Chief Financial Officer)
Numis Securities Limited	Tel: [phone]
Freddie Barnfield / Huw Jeremy (Nominated Adviser)
James Black (Broker)
Consilium Strategic Communications - for UK enquiries	Tel: [phone]
Chris Gardner / Sue Stuart	[e-mail]
Matthew Neal / Olivia Manser

About Ergomed plc

Ergomed provides specialist services to the pharmaceutical industry spanning all phases of clinical development, post-approval pharmacovigilance and medical information. Ergomed's fast-growing, profitable services business includes an industry leading suite of specialist pharmacovigilance (PV) solutions, integrated under the PrimeVigilance brand, a full range of high-quality contract research and trial management services under the Ergomed brand (CRO), and an internationally recognised specialist expertise in orphan drug development, under PSR. For further information, visit: http://ergomedplc.com .

 

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