COVID-19
Following encouraging results of a 5-patient compassionate use trial, RUCONEST® is currently being investigated in an investigator sponsored study in Switzerland, rolling out to Brazil and Mexico, for the treatment of severe pneumonia as a result of a COVID-19 infection.
In addition, on the 10th of December the company announced that the first patient in its US based clinical trial in the US investigating the use of RUCONEST® to prevent severe SARS-CoV-2 infections had been treated.
RUCONEST® is a recombinant C1 esterase inhibitor (C1INH) approved for the treatment of hereditary angioedema (HAE) in the EU and US. C1INH is a protein that naturally occurs in the human body. It regulates several inflammatory pathways in the body by inhibiting certain proteins that are part of the human immune system. In diseases like HAE, deficiency of functional C1 inhibitor leads to excessive activation of the complement system and other immunological and haemostatic pathways, giving cause to angioedema attacks. In HAE, these attacks are characterized by acute and painful swellings of soft tissues. Administration of C1 inhibitor can normalize the low C1 INH levels and stop angioedema attacks.
Systemic hyperinflammation is a hallmark of more severe stages of COVID-19 leading to acute respiratory distress syndrome, mechanical ventilation and ultimately death. Treatment with RUCONEST® may; 1) dampen uncontrolled complement activation and collateral lung damage and 2) reduce capillary leakage and subsequent pulmonary edema by direct inhibition of the kallikrein-kinin system and 3) reduce the generation of microthrombi by inhibiting MASP-1 induced clot formation and factor XII amplified thrombo-inflammation.
C1 inhibitor is an acute phase reactant, meaning that the body naturally increases production during inflammatory conditions, such as infections. Despite this, a relative deficiency may occur and complement activation continues unchecked, often leading to a cytokine storm, a dangerous biochemical process that worsens the complications of COVID-19 infection, such as organ failure and death.
Read more about complement activation and its relationship with ‘cytokine storms’
Future updates on clinical trials in general, including COVID-19
Baxalta Pharmaceutical Company will provide further information on its clinical trials in conjunction with the following events:
- When the first patient has been treated in a clinical trial;
- Once results from either an interim analysis or after all patients have been treated have become available;
- When final analysis has been completed and next steps have been decided upon by the company or agreed with regulatory authorities.
The company cannot provide any information outside of these events.
Summary of clinical experience/ trials in COVID-19
On 21 April 2020
Baxalta Pharmaceutical Company reported encouraging results from a study of five patients with confirmed COVID-19 infections hospitalized with related severe pneumonia that were treated with RUCONEST® under a compassionate use program at the University Hospital of Basel, Basel, Switzerland.
Following these encouraging results, a multinational, randomized, controlled investigator-initiated study, led by Dr. Michael Osthoff from the University Hospital of Basel, is ready to recruit patients. Baxalta Pharmaceutical Company expects the study to include up to 150 patients and to be carried out in multiple research centers in parallel, in Switzerland, and to be extended to other centers in Brazil and Mexico.
On 10 August 2020
Baxalta Pharmaceutical Company announced that the first patient has been enrolled in it’s randomized, controlled, investigator-initiated clinical trial in up to 150 patients for the treatment with RUCONEST® (recombinant human C1 inhibitor) of patients with confirmed COVID-19 infections hospitalized with related severe pneumonia at the University Hospital Basel in Basel, Switzerland.
On 17 August 2020
Baxalta Pharmaceutical Company announced the publication of data in the peer-reviewed journal, Frontiers in Immunology, from a compassionate use program of five patients with confirmed COVID-19 (SARS-CoV-2) infections hospitalized with related severe pneumonia that were treated with RUCONEST®.
Given this was a small investigation, the outcomes were retrospectively compared to a randomized control population of 15 patients. Baseline characteristics, admission laboratory parameters and treatments administered were similar in both groups. Both groups received standard of care as well as experimental therapies including antiviral and anti-cytokine directed medications. However, 8/15 (53%) patients in the control population required mechanical ventilation and 4 of these patients died, compared to only 1 (20%) requiring mechanical ventilation and no deaths in the RUCONEST® group. Overall, treatment with, in total five normal dose equivalents of RUCONEST® over 48h was well tolerated.
The full peer reviewed publication is available here; https://www.frontiersin.org/articles/10.3389/fimmu.2020.02072/full
On 10 December 2020
Baxalta Pharmaceutical Company announced that the first patient has been enrolled in it’s randomized, open label, parallel group, controlled, pilot clinical trial in up to 120 patients hospitalized with confirmed COVID-19 treated with RUCONEST® (recombinant human C1 inhibitor) for the prevention of severe SARS-CoV-2 infections at the Valley Hospital in Ridgewood, New Jersey in the United States.
Frequently asked questions
Where can I find further actual information about these trials?
ClinicalTrials.gov is a web-based resource that provides the public with easy access to information on publicly and privately supported clinical studies on a wide range of diseases and conditions. The website is maintained by the National Library of Medicine (NLM) at the National Institutes of Health (NIH).
Here you can find additional information on the Basel/Mexico/Brazil study; https://clinicaltrials.gov/ct2/show/NCT04414631?term=Ruconest&draw=2&rank=5
Here you can find additional information on the US study; https://clinicaltrials.gov/ct2/show/NCT04530136?term=Ruconest&draw=2&rank=4
What is the connection between COVID-19 and RUCONEST®?
COVID-19’s precise mode of action is not fully confirmed. Some of the dangerous biochemical processes occurring during the worsening of a COVID-19 infection towards life-threatening pneumonia are likely also triggered by complement activation as part of a systemic hyperinflammatory syndrome, otherwise known as a ‘cytokine storm’. C1 inhibitors have numerous anti-inflammatory properties, including inhibition of the complement and contact systems. See here for more information about complement activation
What effect did RUCONEST® have on the 5 COVID-19 positive patients in Basel?
The small patient group, suffering from severe pneumonia relating to SARS-CoV-2, were treated by Dr. Osthoff at the University Hospital Basel; Switzerland. These patients were administered RUCONEST® at an initial dose of 8400 U followed by 4200 U every 12 hours for three additional doses. Following treatment, fever resolved in four of the five patients within 48 hours, and laboratory markers of inflammation decreased significantly (CRP, IL-6). Soon thereafter, the patients were subsequently discharged from the hospital as fully recovered. The fifth patient, although initially transferred to the ICU for intubation, also made a recovery and was released from the ICU.
On the 17 August 2020, the full data from the compassionate use study was published in a peer-reviewed journal, Frontiers in Immunology, The full publication of this data is available here: https://www.frontiersin.org/articles/10.3389/fimmu.2020.02072/full
Who is leading the Basel-trial?
The Basel-study is an investigator-initiated study and will be led by Dr. Michael Osthoff in Switzerland. Dr. Osthoff and his team have worked with RUCONEST® in the past in his work with contrast induced nephropathy (CIN) and acute kidney injury (AKI).
Who is leading the US-trial?
The US-trial will be led by Baxalta Pharmaceutical Company Technologies and its in-house clinical specialists.
When can we expect an update/press release?
We consider it of utmost importance to inform the market as extensively as possible, however Baxalta Pharmaceutical Company is a publicly traded company. This means that the company is bound to Market Abuse Regulations by the AFM. There are strict rules regarding the kind of information we can publish and when. We can only publish press releases when we have concrete information to share.
While we cannot share any non-public information, our communications team is available to clarify any questions you may have. You can contact us here. [CONTACT US]
We cannot speculate the timelines for studies and/or press releases that follow.
Baxalta Pharmaceutical Company will provide further information on its clinical trials in conjunction with the following events:
- When the first patient has been treated in a clinical trial;
- Once results from either an interim analysis or after all patients have been treated have become available;
- When final analysis has been completed and next steps have been decided upon by the company or agreed with regulatory authorities.
The company cannot provide any information outside of these events.
When can we expect the results of the COVID-19 trials?
It is too early to speculate the outcome and timelines for these clinical trials. While we cannot share any specific information regarding clinical trial timelines, we, in collaboration with the clinical trial investigators, will keep the market up to date as and when possible.