Novartis and Incyte Launch Phase III Trial of JAK Inhibitor Jakavi (Ruxolitinib) for Cytokine Storm in Severe COVID-19 Patients Amid Global Pandemic Surge

April 03, 2020 News /BioValleyBIOON/ -- Currently, the COVID-19 epidemic in China has begun to stabilize, but the outbreak abroad is spreading rapidly. According to Baidu's "Real-time Data on the Novel Coronavirus Pneumonia Epidemic"Big DataReport》, as of 11:00 on April 3, 2020, the cumulative number of confirmed cases worldwide exceeded one million, reaching 1.017 million. The cumulative number of confirmed cases outside China surpassed 934,000, with 49,800 deaths.

Among them, the United States reported 25,508 new cases in a single day, bringing the cumulative total to 245,070, making it the country with the highest number of confirmed COVID-19 cases globally. In addition, the number of confirmed cases in several European countries continues to rise, with Italy and Spain exceeding 110,000 cases each, Germany surpassing 80,000, France approaching 60,000, and the United Kingdom at 34,000.

The COVID-19 pandemic situation is unprecedentedly severe, and governments around the world are issuing emergency authorizations to use promising drugs for the treatment of severe COVID-19. Previously, a large number of pharmaceutical companies were rapidly advancing globalClinical Trial, evaluate various new drugs/methods, including Gilead’s antiviral drug remdesivir, Roche’s anti-inflammatory drug tocilizumab, Sanofi/Regeneron’s anti-inflammatory drug Kevzara, and AbbVie’s Kaletra, among others.

Recently, Novartis announced a collaboration with Incyte to launch a Phase IIIClinical Trial(RUXCOVID), evaluating the JAK1/2 inhibitor ruxolitinib (Jakafi/Jakavi) in combination with standard of care (SoC) for the treatment of cytokine storm associated with coronavirus disease 2019 (COVID-19).Cytokine Storm Is a Severe Hyperimmune Response That Can Cause Respiratory System Damage in COVID-19 Patients, Leading to Life-Threatening Respiratory Complications.In this collaborative study, Incyte will sponsor the U.S. region,NovartisWill sponsor the conduct of trials outside the United States.

NovartisThe parties stated that, in light of the rapid spread of the COVID-19 pandemic and as the study protocol was finalized, the company established an international compassionate use program for eligible patients in accordance with local regulations. Incyte Corporation will launch a separate open-label Emergency Access Program (EAP) in the United States. These programs will allow eligible patients with severe COVID-19-associated cytokine storm to access ruxolitinib treatment, even as the parties plan to evaluate ruxolitinib for this indication.

NovartisIncyte stated that the decision to initiate ruxolitinib treatment for COVID-19-associated cytokine storm was based on preclinical evidence and preliminary clinical data from independent studies, indicating that Jakafi/Jakavi may reduce the number of patients requiring intensive care and mechanical ventilation. Furthermore, this decision was also supported by substantial evidence regarding the use of Jakavi/Jakafi in acute graft-versus-host disease (GVHD) and myeloproliferativeTumor...data supporting the safety and efficacy in diseases such as... The proposed trial will evaluate patients with severe COVID-19 caused by SARS-CoV-2 infection, comparing Jakavi/Jakafi in combination with standard of care (SoC) versus SoC alone.

Currently, Incyte is ramping up production to meet anticipated supply demands related to COVID-19 research and is closely monitoring the supply of Jakafi/Jakavi in collaboration with its distribution partners.NovartisIncyte stated that it would take measures to ensure an uninterrupted supply of Jakafi/Jakavi for its currently approved indications.

The active pharmaceutical ingredient of Jakafi/Jakavi is ruxolitinib, a first-in-class oral Janus kinase 1 and Janus kinase 2 (JAK1/JAK2) inhibitor discovered by scientists at Incyte. Overactivated signaling via the JAK-STAT pathway is associated with various cancers, including a group known as myeloproliferativeTumor(MPN) rare blood cancers, as well as other serious immune-mediated diseases, such as graft-versus-host disease (GVHD).

Given that many patients with severe respiratory conditions caused by COVID-19, such as pneumonia, exhibit features consistent with cytokine storm and enhanced activation of the JAK-STAT pathway, it can be hypothesized that ruxolitinib may play a role in the treatment of these patients.

Jakafi/Jakavi has been approved for three indications, including:Myelofibrosis, Polycythemia Vera (PV), Corticosteroid-Refractory Acute Graft-versus-Host Disease (GVHD).In the U.S. market, the drug is marketed under the brand name Jakafi by Incyte; outside the United States, it is marketed under the brand name Jakavi byNovartisSales.

Currently, Incyte Corporation is also developingRuxolitinib Cream, this formulation is in Phase III clinical development: (1) for the treatment of mild toModerate Atopic Dermatitis (TRuE-AD Project)Patient, (2) for the treatment of adolescents and adultsVitiligo(TRuE-V Project)Incyte holds the global rights to develop and commercialize ruxolitinib cream.

In the treatment of vitiligo, Phase II clinical data released in October 2019 showed that, compared with the vehicle control group (drug-free cream), patients treated with ruxolitinib cream demonstrated significant improvement in the Facial Vitiligo Area Scoring Index (F-VASI) and systemicVitiligoRepigmentation of skin lesions showed significant improvement.

In February this year, the Phase III program of ruxolitinib cream for the treatment of adolescent and adult atopic dermatitis (AD) achieved success, confirming the potential of ruxolitinib cream as an important non-steroidal therapeutic option for millions of AD patients. If approved, ruxolitinib cream has the potential to become the first topical JAK inhibitor formulation for AD patients. (Bioon.com)

Original Source:Novartis announces plan to initiate clinical study of Jakavi® in severe COVID-19 patients and establish international compassionate use program