Novartis and Molecular Partners Launch Global Phase 2/3 EMPATHY Trial of Ensovibep, a Multispecific DARPin Antiviral Therapy for Early-Stage COVID-19
May 31, 2021 20:42
CST Updated
20:42
Novartis
Drug Development and Manufacturing
May 31, 2021 Report /BIOON/ -- At present, the COVID-19 epidemic overseas continues to spread rapidly. According to Baidu's "Real-Time Big Data Report on the Novel Coronavirus Pneumonia Epidemic," as of 19:00 on May 31, 2021, global cumulative confirmed cases have exceeded 170 million (171.05 million), with deaths exceeding 3.557 million.
Recently, Novartis and Molecular Partners jointly announced the initiation of the global multicenter Phase 2/3 clinical trial EMPATHY, to exploreNovel DARPin Protein Therapy Ensovibep (MP0420) for the Treatment of COVID-19。Novartis is conducting the ensovibep clinical trial program, with Molecular Partners serving as the sponsor of these studies. In March 2021, Molecular Partners reported positive Phase I results in healthy volunteers.
The EMPATHY clinical trial will be conducted in patients with early-stage COVID-19 infection to evaluate the safety and efficacy of ensovibep in preventing the worsening of COVID-19 symptoms and hospitalization.The study plans to enroll 2,100 patients, with the Phase 2 portion enrolling 400 patients to determine the dose with optimal safety and efficacy. Initial results are expected in August 2021. Subsequently, the Phase 3 portion will enroll 1,700 patients, with results expected in the first half of 2022. Should the preliminary results of the EMPATHY trial prove compelling, this will pave the way for Novartis to seek accelerated approval through the U.S. FDA’s Emergency Use Authorization (EUA).
The inclusion criteria for the EMPATHY trial were: age >18 years, positive SARS-CoV-2 antigen test, and at least two prespecified mild-to-moderate COVID-19 symptoms within 7 days of diagnosis.
Dr. Lutz Hegmann, Head of Enterprise Affairs and Global Health at Novartis, stated: “Novartis remains steadfast in its commitment to helping combat COVID-19, including our support for providing treatment options to patients worldwide. Today, together with Molecular Partners, we announced the next important step for ensovibep, a therapy with the potential to address breakthrough infections and new variants in the future. We hope the results of this clinical trial program will provide reliable treatment options for patients with COVID-19.”
Novartis believes that a multi-pronged strategy is needed to combat COVID-19, leveraging a range of diagnostic and therapeutic solutions tailored to individual patient needs. Every country should have access to effective medicines to treat COVID-19, as the disease continues to spread despite vaccination, and breakthrough infections are likely to continue to occur.
In October 2020, Novartis entered into a collaboration with Molecular Partners to developTwo DARPin protein therapeutics for COVID-19, ensovibep (MP0420) and MP0423, are DARPin-based antiviral therapies that target multiple distinct epitopes on SARS-CoV-2 to enhance antiviral activity and prevent viral escape through mutation.Novartis has obtained an option from Molecular Partners for global licensing rights to two therapies. Molecular Partners will lead the clinical development program through the completion of Phase 1 studies, after which it will be transferred to Novartis to conduct the pivotal EMPATHY clinical trial, with Molecular Partners serving as the sponsor for these trials. Meanwhile, Molecular Partners will continue all remaining preclinical work for MP0423.
DARPin Module Screening (Part 1); Comparison of DARPin Molecules and Monoclonal Antibodies (Part 2) (Click Image to View Larger Version)
DARPin (Designed Ankyrin Repeat Proteins) is a new generation of target-binding proteins, designed from naturally occurring ankyrin repeat proteins. These proteins have naturally evolved to bind targets with high affinity; typically, they are linked to another protein via a fusion domain, anchoring the latter to a specific site.
DARPin therapeutics represent a novel class of protein therapies that will open up additional dimensions of multispecificity and multifunctionality. DARPin drug candidates incorporate multiple engineered ankyrin repeat binding domains capable of targeting up to six or more distinct targets, offering additional benefits compared to conventional monoclonal antibodies or other available protein therapeutics. The DARPin technology serves as a rapid and highly cost-effective discovery engine capable of generating candidates with favorable developability profiles and high production yields.
The DARPin platform technology can expand the application scope of traditional protein and antibody methods,Can rapidly generate diverse multifunctional drug candidates, capable of simultaneously binding to multiple targets.DARPin molecules are constructed from DARPin protein modules., these modules are single-domain proteins, one-tenth the size of a full-length antibody, featuring a conserved framework and a randomized target-binding surface.
Ensovibep Structural Features (Click image to enlarge)
DARPin molecules offer a differentiated approach to treating COVID-19 with a single molecule capable of simultaneously binding to three sites on the SARS-CoV-2 virus, neutralizing it through multiple mechanisms. This provides the potential for broader efficacy in both therapeutic and prophylactic settings, while reducing the likelihood of viral resistance. Furthermore, DARPins are produced via rapid, high-yield microbial fermentation, offering potential speed and cost advantages compared to the mammalian cell culture processes used for antibody manufacturing.
Compared with monoclonal antibodies, DARPin molecules are particularly well-suited for pandemic settings due to their advantages in multispecific target binding, a long half-life that supports sustained activity, and highly scalable production.
Ensovibep is a unique trispecific DARPin protein therapy with synergistic target-binding capabilities., reported one of the strongest viral inhibitory potencies to date. Ensovibep contains three RBD-binding domains. This unique design enhances potency and prevents viral escape via mutation, and has indeed demonstrated potent inhibitory activity against all COVID-19 variants of concern identified to date, with the potential to maintain inhibitory activity against future COVID-19 variants. Such broad-spectrum activity is essential for any therapeutic intervention for COVID-19 patients.
Furthermore,ensovibep also features a half-life-enhanced DARPin domain., this domain binds to human serum albumin (HSA) to support sustained activity. HSA is present at high levels in lung tissue, which may provide additional benefits in respiratory viral diseases. (Bioon.com)
Original Source: Novartis and Molecular Partners announce start of EMPATHY clinical trial for ensovibep for the treatment of COVID-19