Novel Ticagrelor Reversal Agent Wins Place On EMA’s PRIME
Executive Summary
Only two of seven recent applications for entry into the European Medicines Agency’s priority medicines scheme for getting treatments for unmet medical needs to patients faster made the grade.
PhaseBio Pharmaceuticals has won a place on the European Medicines Agency’s PRIME (priority medicines) scheme for PB2452, an investigational treatment for reversing the antiplatelet effects of ticagrelor in patients with major bleeding and in urgent surgery situations.
There are currently no approved reversal agents for ticagrelor or any other antiplatelet drugs, the company said in a statement after receiving designation under PRIME, which is designed to get treatments for unmet medical needs to patients faster.
PhaseBio is one of two companies that have recently won a place on the scheme. The other is AlloVir, for Viralym-M (ALVR105), an allogeneic, off-the-shelf, multi-virus specific T-cell therapy targeting a number of common viral pathogens in immunocompromised individuals.
PB2452 and Viralym-M were accepted onto the scheme last month. They were among seven applications for investigational products that the EMA assessed for PRIME designation in January. The other five applications were rejected.
PRIME offers developers enhanced scientific and regulatory support from the EMA to help optimize their development plans, and the likelihood of having their product reviewed under the EU’s accelerated assessment procedure when it is eventually filed for regulatory review.
The scheme has tough entry criteria and applicants must convince the EMA that their products have the potential to benefit patients with an unmet medical need based on early clinical data.
Reversal Agent For Ticagrelor
PB2452, a novel, recombinant, human monoclonal antibody antigen-binding fragment, was accepted onto PRIME for the reversal of antiplatelet effects of ticagrelor in patients with uncontrolled major or life-threatening bleeding or requiring urgent surgery or an invasive procedure.
The EMA acknowledged that while ticagrelor-related major bleeding events are infrequent, they are associated with relevant morbidity and mortality, PhaseBio said, adding that the agency also recognized that there are no established effective treatment options to reverse ticagrelor-induced platelet inhibition. “Urgent surgical interventions (such as coronary artery bypass grafting) that cannot be delayed to allow full washout of ticagrelor are associated with an increased risk for intra- and post-procedural bleeding events,” the company said.
Commenting on the study data used to support its PRIME application, PhaseBio said that PB2452 results from the recently completed Phase IIa study demonstrated immediate and sustained reversal of the antiplatelet effects of ticagrelor in older and elderly patients treated with dual antiplatelet therapy (low-dose aspirin and ticagrelor) and in healthy subjects treated with supratherapeutic doses of ticagrelor.
“The clinical data corroborated non-clinical findings that were also reviewed [by the agency], which demonstrated selective, high-affinity binding of PB2452 to ticagrelor and its active metabolite and its potential to provide rapid reversal of ticagrelor. Additionally, EMA cited literature evidence indicating that the platelet-function assays utilized in the PB2452 development program are likely to be predictive of clinical outcomes in cardiovascular patients.”
Development Program On Track
In addition to announcing its PRIME designation, PhaseBio said it had received encouraging scientific advice from the EMA about its overall development program for PB2452, which the company is also planning to take to the US market.
Based on the scientific advice and prior interactions with the US Food and Drug Administration, the company believes its development plan is sufficient to support regulatory filings in both the EU and the US.
It said that the EMA appeared to be aligned with its plan to conduct a non-randomized, open-label Phase III trial of major bleeding and urgent surgical populations to support a pan-EU marketing authorization application (MAA) for PB2452.
Regarding the overall number of patients targeted to participate in the Phase III trial, the company said that the agency agreed with its proposal to conduct the trial in a total of 200 patients, with results from the first 100 patients expected to be included in the MAA package seeking conditional marketing authorization (CMA).
In the US, PB2452 last year received breakthrough therapy designation under the FDA’s program for expediting the development and review of drugs that target serious or life-threatening conditions. PhaseBio said it planned to start its single pivotal Phase III clinical trial of PB2452 in the first quarter of 2020 to support a biologics license application for the product in both major bleeding and urgent surgery indications.
Viralym
As for AlloVir’s Viralym, the investigational cell therapy was accepted onto PRIME for the treatment of serious infections with BK virus, cytomegalovirus, human herpes virus-6, Epstein Barr virus, and/or adenovirus in allogeneic HSCT (hematopoietic stem cell transplantation) recipients.
In the US, the company received regenerative medicine advanced therapy (RMAT) designation from the FDA for Viralym-M last June; the RMAT program is designed to expediate the availability of promising regenerative medicinal products to patients with serious conditions.
AlloVir last year became a portfolio company of cell and gene therapy holding company ElevateBio.
Five Rejected Applications
Applications for PRIME are decided on during the monthly meetings of the EMA's drug evaluation committee, the CHMP. The applications for PB2452 and Viralym were accepted for the scheme during the CHMP's 27-30 January meeting. The five applications that were turned down covered investigational products for the following indications:
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Treatment of no-option patients with critical limb ischemia.
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Treatment of patients with septic shock induced by endotheliopathy.
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Treatment and prevention of complications associated with severe infections, in particular organ failure associated with severe pneumonia.
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Treatment in combination with standard chemoradiotherapy of patients with histologically confirmed diagnosis of previously untreated and unresectable locally advanced squamous cell carcinoma of the head and neck.
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Treatment of patients with Duchenne muscular dystrophy.