Latest news with #monoclonal antibody
Medscape
24-07-2025
- Health
- Medscape
Monoclonal Antibody Shows Promise in Cardiogenic Shock
Treatment with a novel monoclonal antibody against circulating dipeptidyl peptidase 3 (cDPP3) led to complete reversal of cardiogenic shock in three compassionate use cases in Germany, according to a new research letter. The cases mark the first time the intervention has been used to treat cardiogenic shock in humans. Only one of the patients survived, however. 'The findings are highly promising and represent a significant step forward in causally addressing cardiogenic shock, a condition with limited treatment options and high mortality,' Mahir Karakas, MD, of the University Medical Center Hamburg-Eppendorf, Hamburg, Germany, told Medscape Medical News . He is the chief technology officer of 4TEEN4 Pharmaceuticals GmbH, the pharmaceutical company developing the monoclonal antibody called procizumab. 'Out-of-the-Box' Approach The mortality rate of cardiogenic shock exceeds 50%, and current interventions treat only symptoms rather than addressing the root cause, said Alexandre Mebazaa, MD, PhD, of the Université Paris Cité in Paris, France, and a coauthor on the letter. Recent research has revealed a strong link between elevated cDPP3 and higher mortality rates in patients with cardiogenic shock. Procizumab targets DPP3, an enzyme released during cell death that breaks down angiotensin II and disrupts the renin-angiotensin-aldosterone system. By blocking this enzyme's activity, procizumab 'is intended to rapidly stabilize hemodynamics and therefore cardiovascular and renal function,' Mebazaa and his colleagues wrote. 'With these three cases, we [were] really thinking outside of the box, saying, 'There is a protein that is toxic inside the blood: let's inactivate it and see what we can do,'' Mebazaa told Medscape Medical News . The research letter, published online on July 10 in the European Journal of Heart Failure , documented the treatment of three patients in critical condition with signs of multiorgan failure due to refractory septic shock. Patient 1 (age 64 years) and patient 3 (age 80 years) were women; patient 2 (age 84 years) was a man. All conventional therapies had been tried in these patients 'with no further options for escalation of conventional therapy in the presence of a high chance of immediate mortality,' the authors wrote. All three patients had elevated DPP3 activity, acute kidney injury, and needed renal replacement therapy. Patients 1 and 2 were intubated and received mechanical ventilation. Procizumab was administered at a 10 mg/kg dose over 2 hours, and patients were followed for 48 hours. Efficacy was assessed by shock reversal, defined as a norepinephrine dose of 0.2 µg/kg/min or less, or a reduction by at least half of the initial dose. A decline in DPP3 activity over 2 days was accompanied by a marked reduction in norepinephrine dose and lactate concentrations. All three patients demonstrated improved arterial oxygen partial pressure/fractional inspired oxygen ratios, a measure to assess hypoxemia, compared with baseline. Early, but 'Impressive' Findings 'These very early findings support the potential of this specific anti-DPP3 antibody, procizumab, which has previously been shown in animal studies in septic and cardiogenic shock,' said Holger Thiele, MD, director of the Heart Center Leipzig at the University of Leipzig, in Leipzig, Germany, who was not involved with the case study. Both Thiele and the authors acknowledged the uncontrolled design and small sample size preclude any firm conclusions around the potential efficacy of the treatment. 'This is far too early to draw conclusions [about whether] all these effects are related to procizumab, although the drop in [interleukin 6] IL-6 and the improvement in renal function are impressive,' Thiele said. 'However, like always with promising devices or drugs, initial results are often too good to be true. We have to wait for the phase 2, and more importantly, the phase 3 trials to see if this drug in cardiogenic shock or septic shock is able to reduce the mortality.' Two of the patients who received the treatment died less than 2 weeks later: one from recurrent shock likely due to papillary muscle rupture from untreated myocardial infarction (MI), and another from refractory shock due to exacerbation of right heart failure. Patient 2 recovered organ function and was transferred to rehab at 8 weeks despite a new MI at week 4, the researchers reported. 'That two of the three patients had refractory shock again is the typical nature of these severely ill patients,' Thiele said. 'This probably will also be one of the challenges to show a possible benefit of this drug in the subsequent phase 2 and phase 3 trials.' Ongoing Trial Mebazaa is now leading a phase 1b trial to evaluate the safety and tolerability of procizumab as well as the ideal dose for a phase 2 trial. The study, PROCARD 1b, aims to enroll 130 patients with cardiogenic shock due to acute coronary syndrome or sepsis with elevated DPP3. 'It is most likely that specific cutoffs for DPP3 are required,' Thiele said; while too low of a concentration will probably show no benefit, 'too high with too many organ dysfunctions may also result in neutral results. Therefore, a well-designed trial for phases 2 and 3 is of paramount importance.'
Medscape
17-07-2025
- Health
- Medscape
Lebrikizumab Shows Cost Benefits in Atopic Dermatitis Care
TOPLINE: The introduction of lebrikizumab, a novel monoclonal antibody targeting interleukin-13 for severe atopic dermatitis (AD), was associated with cost savings of approximately €3.3 million over 3 years for the Italian National Healthcare System, according to a budget impact analysis model. The adoption of lebrikizumab increased from 1198 patients in year 1 to 5849 patients by year 3, resulting in cumulative savings through reduced drug acquisition and adverse event management costs. METHODOLOGY: This budget impact analysis model compared two scenarios over 3 years from the Italian National Healthcare System perspective: scenario A with current standard biologic agents (dupilumab and tralokinumab) and scenario B including lebrikizumab alongside existing treatments. This analysis included 11,978 patients with severe AD eligible for systemic therapy, with projected growth to 14,973 patients in the first year, 18,716 in the second year, and 23,395 in the third year. Market shares for dupilumab, tralokinumab, and, in the intervention scenario, lebrikizumab were applied to the eligible population annually. The model incorporated drug acquisition, disease management, and adverse event management costs. A one-way sensitivity analysis was conducted to assess the model's robustness by evaluating the impact of individual parameters with ±20% variation. TAKEAWAY: The implementation of lebrikizumab resulted in an expenditure of €785,594 in the first year, followed by €1,693,126 in the second year and €2,395,402 in the third year, totalling approximately €3.3 million over the 3-year period. A market penetration analysis showed that lebrikizumab usage increased from 8% in year 1 to 25% by year 3, whereas dupilumab usage decreased from 74% in year 1 to 59% by year 3 and tralokinumab usage decreased from 18% to 16%. Sensitivity analyses revealed that the number of eligible patients and injection site reaction costs were the primary drivers of the cost-saving findings. Adverse event management costs decreased by €490,817 cumulatively. In scenario B, the number of patients treated with lebrikizumab increased from 1198 in the first year to 5849 in the third year. IN PRACTICE: "The introduction of lebrikizumab in Italy could reduce the overall costs for patients with severe AD, who can be treated with biologic agents, in line with AIFA [Italian Medicine Agency] reimbursement criteria. Lebrikizumab is associated with improved patient management and cost saving for the Italian NHS [National Healthcare System]. This data could serve as valuable information for healthcare decision makers to optimize the value derived from the treatment and management of patients with severe AD," the authors of the study wrote. SOURCE: This study was led by Ippazio Cosimo Antonazzo, Research Centre on Public Health (CESP), University of Milano-Bicocca, Monza, Italy. It was published online on July 09, 2025, in Dermatology and Therapy. LIMITATIONS: The analysis was based on projected utilisation rates of lebrikizumab, which may not be generalisable to populations with different adoption rates of the drug. The analysis was restricted to monoclonal antibodies and did not include JAK inhibitors, which could have resulted in a different economic impact. Additionally, this study considered only direct medical costs from the Italian National Healthcare System perspective, excluding patient-incurred costs or potential savings from accessing lebrikizumab. DISCLOSURES: This study was supported by Almirall S.p.A., Milan, Italy. Several authors reported receiving grants and personal fees and having other ties with various sources. Additional disclosures are noted in the original article. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
