An Open-label, Phase 2 Trial to Evaluate the Efficacy and Safety of a Single Intravenous Administration of GNT0003 (an Adeno-associated Viral (AAV) Vector Expressing the UGT1A1 Transgene) Following Imlifidase Pre-treatment in Adult Participants With Severe Crigler-Najjar Syndrome (CNS) Requiring Daily Phototherapy and Presenting Pre-existing Anti-AAV8 Antibodies

Clinical trial rationale:
CNS is an ultra-rare (<1/1 million newborns), autosomal recessive disorder of bilirubin conjugation caused by mutation in the gene coding for uridine 5'-diphosphate glucuronosyltransferase (UGT1A1), that causes the accumulation of neurotoxic unconjugated bilirubin (UCB).
Reduction of UCB is managed with phenobarbital in mild CNS, and daily phototherapy in severe CNS.
There is no authorized curative medical treatment for CNS. Liver transplantation is currently the only curative treatment for severe CNS.
GNT0003 is a genetically modified recombinant (r) viral vector composed of the AAV8 viral capsid carrying the UGT1A1 transgene which aims to correct the dysfunction of the mutated gene by achieving durable expression of a functional copy of the affected gene.
Imlifidase (IgG-degrading enzyme) has demonstrated its efficacy in highly sensitized adult kidney transplant patients.
To give participants with pre-existing anti-AAV8 antibodies access to gene therapy treatments, this trial aims to demonstrate the safety and efficacy of GNT0003 following imlifidase pre-treatment in adult participants with severe CNS requiring daily phototherapy and presenting with pre-existing anti-AAV8 antibodies.
Primary objective: to assess efficacy of a single intravenous administration of GNT0003 following imlifidase pre-treatment in participants with severe CNS requiring phototherapy and pre-existing AAV8 antibodies
Secondary objective: to collect data on safety and tolerability of GNT0003 and imlifidase, efficacy of imlifidase, pharmacokinetic and pharmacodynamic profile of GNT0003, and Quality of Life.
The trial will include 3 parts:
* A baseline period for at least 3 months
* A treatment period
* A follow-up period:
* Initial post-treatment follow-up over 48 weeks
* Long-term follow-up for 4 additional years
This trial will be conducted in accordance with the International Conference on Harmonization Guideline for Good Clinical Practice and the Declaration of Helsinki. Participants must be consented using the approved Informed Consent Form before any procedures specified in the protocol are performed.

开始日期2024-11-08

申办/合作机构

Genethon

[+1]

NCT06461546

/ Withdrawn临床2期IIT

Imlifidase in Living Donor Renal Transplantation Highly Sensitized Recipients (LIVEDES)

This is a Phase II, pilot, prospective, unicentric trial, to evaluate Imlifidase could improve the transplantability of the highly sensitized patients with good outcomes respect to survival and functionality of the graft.

开始日期2024-10-22

申办/合作机构-

NCT06241950

/ Enrolling by invitation临床1期

An Open-Label, Systemic Gene Delivery Study to Evaluate the Safety, Tolerability and Expression of SRP-9001 in Association With Imlifidase in Subjects With Duchenne Muscular Dystrophy With Pre-existing Antibodies to rAAVrh74

This is a gene transfer therapy study evaluating the safety of delandistrogene moxeparvovec and delandistrogene moxeparvovec dystrophin expression in association with imlifidase, in participants with DMD with pre-existing antibodies to rAAVrh74 over a period of 104 weeks.

开始日期2024-01-29

申办/合作机构

Sarepta Therapeutics, Inc.

[+1]

100 项与 Imlifidase 相关的临床结果

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100 项与 Imlifidase 相关的转化医学

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100 项与 Imlifidase 相关的专利（医药）

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128

项与 Imlifidase 相关的文献（医药）

2025-11-01·KIDNEY INTERNATIONAL

A multicenter prospective cohort study evaluating impact of an active delisting strategy to enable kidney transplantation in wait-listed candidates with calculated Panel Reactive Antibody ≥ 99.9%

Article

作者: Cucchiari, David ; Arana, Carolt ; Mancebo-Sierra, Esther ; Meneghini, Maria ; Moreso, Francesc ; Pérez-Saez, María José ; Andrés, Amado ; Diekmann, Fritz ; Caro, José Luis ; López, Beatriz Romero ; Palou, Eduard ; Redondo-Pachón, Dolores ; Crespo, Marta ; Bestard, Oriol

INTRODUCTION:

In kidney transplant candidates with calculated Panel Reactive Antibody (cPRA)≥99.9%, looking for perfect HLA compatibility may delay transplantation beyond a reasonable waiting time. However, the presence of preformed donor-specific antibody (DSA) does not always lead to antibody-mediated rejection. Here, we present the results of a delisting strategy for kidney transplant candidates with cPRA≥99.9% employed in four Spanish transplant centers May 2022-August 2023.

METHODS:

Briefly, HLA antigens were delisted if their mean fluorescence intensity (MFI) in current and historical samples was lower than 5,000, with the goal to decrease cPRA to ≤99.0%. If this first step was unsuccessful, HLA antibodies with an MFI under 10,000, or any MFI for anti-HLA-DP and anti-HLA-DRB3/4/5 were considered for delisting. Additional criteria included their 1/16 dilutions response and complement-binding activity (C3d or C1q), ideally avoiding antibodies targeting a cross-reactive epitope groups/eplet pattern and repeated mismatches with previous donors.

RESULTS:

In total, 48 patients underwent HLA-antigen delisting after a median 5.6 years on the waiting list, lowering their cPRA to 98.3%. Thirty (62.5%) patients received an acceptable donor offer 98[52-154] days after delisting, of which 18 (60.0%) had negative flow cytometry and complement-dependent cytotoxicity crossmatches and underwent direct transplantation without additional desensitization with the enzyme imlifidase. Among these, sixteen patients (83.3%) had at least one preformed DSA, with an immunodominant MFI of 7245[3857-18322]. In these patients, after one-year follow-up, antibody-mediated rejection occurred in seven cases (43.7%) and graft survival was 87.5%.

CONCLUSIONS:

Our study shows that careful antigen delisting enhances access to transplantation for patients with cPRA ≥99.9%. While this approach carries a significant risk of acute rejection, it is associated with reasonable short-term graft survival.

2025-10-01·Kidney Medicine

Desensitization With Imlifidase: Overcoming Immunological Barriers in Kidney Transplantation

Article

作者: González-García, Celia ; Polanco Fernández, Natalia ; Hernández-Velasco, Paul José ; Gutiérrez Martínez, Eduardo ; González Monte, Maria Esther ; Andrés Belmonte, Amado ; Mancebo Sierra, Esther

Highly sensitized patients without compatible living donors face prolonged waiting times for a transplant. Prioritization and desensitization strategies often prove insufficient because of logistical challenges, extended treatments, and increased infection risk. The new drug imlifidase offers an opportunity for these patients by rapidly removing IgG antibodies, enabling desensitization when a donor is available. However, real-word experience remains limited. Here, we present the first case in Spain, outside of a clinical trial, in which imlifidase desensitization allowing a kidney transplant in a woman with a calculated panel reactive antibody >99.99%, requiring a second kidney transplant after 13 years on dialysis. After anti-human leukocyte antigen antibodies delisting (<20,000 mean fluorescence intensity [MFI], responders to dilution and noncomplement fixing), she received a deceased-donor kidney against whom she had 6 donor-specific antibodies (DSAs; ranging from 3,049 to 12,001 MFI; targeting human leukocyte antigen class I and II) and a positive flow cytometry crossmatch-all becoming negative after treatment with imlifidase. Early post-transplant DSA rebound was managed with conventional desensitization and anti-C5 blockade. Short-term outcomes were encouraging, with stable kidney function and significant DSA reduction at 9 months. This case highlights the potential of imlifidase in highly sensitized patients; however, long-term studies remain essential to optimize monitoring and concomitant desensitization protocols.

2025-10-01·Clinical transplantation and research

Refractory antibody-mediated rejection after high-emergency lung transplantation for dermatomyositis with anti-MDA5 antibody: a case report

Article

作者: Godet, Cendrine ; Comarmond, Chloé ; Borie, Raphael ; Mordant, Pierre ; Taupin, Jean-Luc ; Weisenburger, Gaelle ; Salpin, Mathilde ; Cazes, Aurélie ; Mal, Hervé ; Alexandra, Jean-François ; Messika, Jonathan ; Mouren, Domitille ; Chantelot, Louise ; Uzunhan, Yurdagül ; Roux, Antoine ; Lortat-Jacob, Brice ; Bunel, Vincent ; Allenbach, Yves

This case report describes a female with amyopathic anti-MDA5+ dermatomyositis who underwent emergency double lung transplantation due to rapidly progressive interstitial lung disease. Following transplantation, she developed acute antibody-mediated rejection (AMR). Despite multiple rounds of immunosuppressive therapy, her condition continued to deteriorate, and her donor-specific anti-human leukocyte antigen antibody levels increased markedly. An experimental treatment, imlifidase-an immunoglobulin G endopeptidase-was employed as a rescue therapy. This case highlights the complexity of posttransplant management of AMR and emphasizes the need for dedicated clinical trials to provide additional data.

项与 Imlifidase 相关的新闻（医药）

2025-10-10

·EndPoints

Person previously ineligible for gene therapy granted treatment after antibody-chopping drug clears the way

SEVILLE, SPAIN — Gene therapies are offering new hope to some patients with rare disease, but not everyone. A third or more of patients are often turned away because they’ve already been infected with natural versions of the viruses used to shuttle therapeutic genes into cells. Antibodies developed from those prior viral exposures would render the gene therapy ineffective, and potentially unsafe. But a new study from the French research institute Genethon and the Swedish company Hansa Biopharma suggests a way to overcome that restriction. Jeremy Do Cao, a pediatrician at Antoine-Béclère Hospital in Paris, tested a new approach in a 22-year-old woman who was previously ineligible to participate in a clinical trial of Genethon’s gene therapy for her ultra-rare disease, Crigler–Najjar syndrome. That disease is caused by mutations that break an enzyme essential for metabolizing bilirubin. Genethon’s gene therapy, called GNT003, uses the viral vector AAV8 to deliver the genetic instructions for making the bilirubin-busting enzyme. The patient was excluded from the original trial because she had antibodies to AAV8, but she was included in a new study that used a bacteria-derived enzyme called imlifidase, marketed as Idefirix by Hansa, to temporarily clear out those antibodies, Do Cao told Endpoints News . After receiving that imlifidase pretreatment, the patient got Genethon’s gene therapy, which appeared to at least partially work by temporarily lowering her bilirubin levels. Do Cao presented the results on Friday at the annual meeting of the European Society of Gene and Cell Therapy in Spain. “This is the first time we have seen a patient treated with AAV vectors that already had pre-exposure to AAVs,” Giuseppe Ronzitti, a researcher at Genethon who was part of the study, told Endpoints. Ronzitti admits there are still many unanswered questions about the approach, including whether it will work for all varieties of AAV vectors and any kind of disease. He said that a small subset of people have very high levels of anti-AAV antibodies, and it is unclear if imlifidase pretreatment will work for these patients. It is also unknown if the strategy could enable redosing of AAV gene therapies, which is currently impossible since patients acquire immunity to the virus after treatment. “The important thing is to continue this clinical testing,” Ronzitti said. There are plans to enroll two more patients in the Crigler–Najjar syndrome study, he added. If bilirubin levels are left unchecked in people with Crigler–Najjar syndrome, the molecule can cause irreversible brain damage. Blue light phototherapy can turn bilirubin into a form that is more readily excreted from the body, but the process is time-consuming, akin to lying in a tanning bed for half a day. “Imagine sleeping under them for 12 hours every night of your life to be able to function normally and not have any neurological impairment,” Do Cao said in his presentation. That is what his patient had to do, and a primary goal of the new study was to see if the gene therapy would eliminate the need for phototherapy, he added. The patient was given an infusion of imlifidase, along with an allergy medicine and a steroid, two days before receiving the gene therapy infusion. Antibodies targeting AAV8 plummeted briefly before jumping back four days later as the imlifidase wore off. Her bilirubin levels also dropped within a week, suggesting that the viral vector successfully delivered the therapeutic gene to the liver. Bilirubin levels remained lower for about three months as the patient continued undergoing daily phototherapy. But when she reduced and then stopped phototherapy, her bilirubin levels shot back up to the baseline levels she previously maintained. That allowed her to go on her honeymoon free from the blue lights, Do Cao said. Nicola Brunetti-Pierri, a pediatrician and geneticist from Telethon Institute of Genetics and Medicine in Italy who wasn’t involved in the study, told Endpoints that the rise in bilirubin levels suggests that some expression of the gene therapy diminished over time. But he said it doesn’t necessarily mean that the anti-AAV8 antibodies — which came back at much higher levels than baseline — are responsible. “It may be dependent on other issues,” Brunetti-Pierri said. “It is a single patient, so it’s hard to draw conclusions. But the first results are in a way promising.” The imlifidase treatment seemed safe, and the temporary depletion of antibodies didn’t cause an infection, although the patient also received antibiotics as a precaution. The patient experienced two moderate and two mild episodes of liver enzyme elevations that are sometimes seen after gene therapy infusion and can suggest liver damage and inflammation. There were no severe adverse events. Hansa originally developed imlifidase as a way to clear antibodies prior to kidney transplantation and has a conditional approval for the drug in the EU. The company also has agreements with AskBio, Genethon and Sarepta to test the enzyme as a pretreatment in gene therapy. “Our intention is to prove that we can remove antibodies prior to different gene therapies and extend the label for imlifidase with those different applications,” Lena Winstedt, vice president, head of scientific affairs at Hansa, told Endpoints. “We’re pretty sure that if it works with one vector, it would work with another vector.” Paris-based Vivet Therapeutics is working on its own version of imlifidase, dubbed VTX-PID. On Thursday at the conference, Vivet CEO Jean-Philippe Combal presented the results of a Phase 1 study in healthy volunteers showing that his company’s drug could reduce anti-AAV3B antibodies and provide a window of two to five days for a potential gene therapy administration. But Vivet’s drug didn’t lower antibody levels far enough in patients who had high levels of antibodies — specifically an antibody titer of 1/100. That was the same antibody titer that the patient in the Genethon and Hansa study had. Both Combal and Ronzitti independently told Endpoints that antibody titers are measured differently in different labs and it is hard to compare across studies. “There exists no validated, standardized test that works for every capsid, every AAV,” Ronzitti said. “That’s where the complication lies.”

基因疗法临床1期临床结果

2025-10-10

·Business Wire

Data from GNT-018-IDES Trial Supports Feasibility of imlifidase as Pretreatment in Gene Therapy Treatment for Patients With Crigler–Najjar Syndrome Who Are Immune to AAV

PARIS--(BUSINESS WIRE)--Genethon, a worldwide pioneer and leader in research and development of gene therapy for rare genetic diseases, and Hansa Biopharma, a Sweden-based leader in IgG cleaving enzyme technology announced today that a patient with a rare liver disease and immunity to the AAV vector has been successfully treated with Genethon’s AAV-based GNT0003 gene therapy for Crigler-Najjar syndrome, following prior administration of imlifidase, an enzyme capable of temporarily inhibiting the immune response. This encouraging result, achieved in a clinical trial, is a significant advance in the treatment of patients with immunity to AAVs who were previously ineligible for clinical trials and existing gene therapy treatments. Gene therapy involves injecting a gene drug into an organism using a vector, a "means of transport" usually derived from viruses, such as AAVs (adeno-associated viruses), which are commonly used for gene therapy in for example neuromuscular, liver, and eye diseases. Initial contact with the natural virus can cause the body to develop immunoglobulin G (IgG) antibodies that neutralize AAVs. It is estimated that one in three people is naturally immune to AAVs, thereby excluding a large number of patients from the possibility of benefiting from gene therapy using an AAV vector. To evaluate potential options for treating patients with natural immunity to AAVs, researchers at Genethon tested imlifidase, an enzyme developed by Hansa Biopharma, as a pre-treatment. This enzyme is capable of cleaving IgG, thereby rapidly and significantly reducing the level of anti-AAV antibodies and allowing the administration of a gene therapy drug candidate. Dr. Jérémy Do Cao (Béclère Hospital, AP-HP, France) presented at the 2025 congress of the European Society of Gene & Cell Therapy (ESGCT), the results of using imlifidase as a pre-treatment for GNT0003 gene therapy in a patient with a severe form of Crigler–Najjar syndrome who is naturally immune to the AAV8 vector, as part of the clinical trial (GNT-018-IDES) conducted by Genethon in collaboration with Hansa Biopharma. In this first patient treated, the study demonstrated: - the feasibility and safety of this approach: imlifidase administered prior to GNT0003 gene therapy successfully cleaved and inactivated the patient's antibodies and enabled treatment with GNT0003. No severe side effects related to GNT0003 or imlifidase were reported. - initial efficacy data: GNT0003, Genethon’s gene therapy drug candidate significantly lowered the patient's bilirubin levels, enabling her to stop hours of daily phototherapy, which had been essential to her survival until then. The phototherapy has been interrupted sixteen weeks after the injection, as planned in the protocol. Additional data will be needed to confirm this efficacy in the longer term. This is the first time that gene therapy has been successfully administered to a patient with Crigler–Najjar syndrome who has antibodies against AAV8. If the results are confirmed in the next stages of the trial, this approach could become a promising option for patients with antibodies to AAVs, who are currently ineligible for clinical trials and existing gene therapy treatments. "It's incredible to have had the chance to witness the clinical translation of this project, which I saw come to life in our laboratory,” said Giuseppe Ronzitti, Head of the Immunology and Liver Disease Laboratory and Director of Scientific Forecasting at Genethon. “It's a project that involved a significant portion of Genethon working toward a common goal. The preliminary data we've obtained indicate that we still have a lot to learn about the immune response to AAV vectors, but the solution is potentially there." About imlifidase Imlifidase is a unique antibody-cleaving enzyme, originating from Streptococcus pyogenes, that specifically targets IgG and inhibits the IgG-mediated immune response. (6) It has a rapid onset of action, cleaving IgG antibodies and inhibiting their activity within hours of administration. Imlifidase has conditional marketing approval in EU, Norway, Iceland, Lichtenstein and the UK and is marketed under the trade name IDEFIRIX® for the desensitization treatment of highly sensitized adult kidney transplant patients with a positive crossmatch against an available deceased donor. (6) Is also approved in Switzerland and Australia. About GNT003 The drug candidate GNT-0003, developed by Genethon to treat Crigler-Najjar syndrome, is currently being evaluated in a trial (GNT-012-CRIG) conducted in France, the Netherlands, and Italy in patients with no pre-existing immunity to AAV, with encouraging results. (5) About Crigler-Najjar syndrome Crigler-Najjar syndrome is a rare genetic liver disease characterized by abnormally high levels of bilirubin in the blood (hyperbilirubinemia), which leads to irreversible neurological damage manifested as muscle weakness, lethargy, deafness, mental retardation, and eye movement paralysis. This accumulation of bilirubin is caused by a deficiency of the UGT1A1enzyme, responsible for transforming bilirubin into a substance that can be eliminated by the body. It can result in significant neurological damage and death if not treated quickly. At present, patients must undergo prolonged daily phototherapy (often more than 10 hours a day, sometimes up to 15 hours a day) to keep their bilirubin levels below the toxicity threshold. Crigler-Najjar syndrome is an ultra-rare disease affecting less than one in one million people per year. Liver transplantation remains the only definitive cure to date, but is associated with significant morbidity and mortality, as well as graft shortage. (7) About Hansa Biopharma Hansa Biopharma AB is a pioneering commercial-stage biopharmaceutical company on a mission to develop and commercialize innovative, lifesaving and life-altering treatments for patients with rare immunological conditions. The company has a rich and expanding research and development program based on proprietary IgG-cleaving enzyme technology platform, to address serious unmet medical needs in autoimmune diseases, gene therapy and transplantation. The company’s portfolio includes imlifidase, a first-in-class immunoglobulin G (IgG) antibody-cleaving enzyme therapy, which has been shown to enable kidney transplantation in highly sensitized patients and HNSA-5487, a next-generation IgG cleaving molecule with redosing potential. Hansa Biopharma is based in Lund, Sweden, and has operations in Europe and the United States. The company is listed on Nasdaq Stockholm under the ticker HNSA. Find out more at https://www.hansabiopharma.com/ and on LinkedIn. About Genethon A pioneer in the discovery and development of gene therapies for rare diseases, Genethon is a nonprofit laboratory created by the AFM-Telethon. A first gene therapy drug, to which Genethon contributed, has been approved for marketing for spinal muscular atrophy. With more than 240 scientists and experts, Genethon's goal is to develop innovative therapies that change the lives of patients suffering from rare genetic diseases. Thirteen gene therapy products developed by Genethon or to which Genethon has contributed are currently undergoing clinical trials for diseases of the liver, blood, immune system, muscles, and eyes. Seven other products are in preparation for clinical trials over the next five years. Find out more on visit http://www.genethon.com References 1. Boutin S, et al. Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum Gene Ther. 2010 Jun;21(6):704-12. doi: 10.1089/hum.2009.182. PMID: 20095819. 2. Calcedo R, Wilson JM. Humoral Immune Response to AAV. Front Immunol. 2013 Oct 18;4:341. doi: 10.3389/fimmu.2013.00341. PMID: 24151496; PMCID: PMC3799231. 3. Veron P, Leborgne C, Monteilhet V, Boutin S, Martin S, Moullier P, Masurier C. Humoral and cellular capsid-specific immune responses to adeno-associated virus type 1 in randomized healthy donors. J Immunol. 2012 Jun 15;188(12):6418-24. doi: 10.4049/jimmunol.1200620. Epub 2012 May 16. PMID: 22593612. 4. Kruzik A, et al. Prevalence of Anti-Adeno-Associated Virus Immune Responses in International Cohorts of Healthy Donors. Mol Ther Methods Clin Dev. 2019 Jun 7;14:126-133. doi: 10.1016/j.omtm.2019.05.014. PMID: 31338384; PMCID: PMC6629972. 5. ClinicalTrial.gov ID: NCT03466463 6. European Medicines Agency. Idefirix® summary of product characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/idefirix-epar-product-information_en.pdf. 7. https://www.genethon.com/our-pipeline/crigler-najjar-syndrome/ 8. Lundstrom K. Viral Vectors in Gene Therapy: Where Do We Stand in 2023? Viruses. 2023 Mar 7;15(3):698. doi: 10.3390/v15030698. PMID: 36992407; PMCID: PMC10059137. 9. Boutin S, et al. Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum Gene Ther. 2010 Jun;21(6):704-12. doi: 10.1089/hum.2009.182. PMID: 20095819. 10. Calcedo R, Wilson JM. Humoral Immune Response to AAV. Front Immunol. 2013 Oct 18;4:341. doi: 10.3389/fimmu.2013.00341. PMID: 24151496; PMCID: PMC3799231. 11. Veron P, Leborgne C, Monteilhet V, Boutin S, Martin S, Moullier P, Masurier C. Humoral and cellular capsid-specific immune responses to adeno-associated virus type 1 in randomized healthy donors. J Immunol. 2012 Jun 15;188(12):6418-24. doi: 10.4049/jimmunol.1200620. Epub 2012 May 16. PMID: 22593612. 12. Kruzik A, et al. Prevalence of Anti-Adeno-Associated Virus Immune Responses in International Cohorts of Healthy Donors. Mol Ther Methods Clin Dev. 2019 Jun 7;14:126-133. doi: 10.1016/j.omtm.2019.05.014. PMID: 31338384; PMCID: PMC6629972. 13. Falese L, et al. Strategy to detect pre-existing immunity to AAV gene therapy. Gene Ther. 2017 Dec;24(12):768-778. doi: 10.1038/gt.2017.95. Epub 2017 Nov 6. PMID: 29106404; PMCID: PMC5746592. 14. Leborgne C, et al. IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies. Nat Med. 2020 Jul;26(7):1096-1101. doi: 10.1038/s41591-020-0911-7. Epub 2020 Jun 1. PMID: 32483358. 15. Au H.K, et al. (2022) Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings. Front. Med. 8:809118. doi: 10.3389/fmed.2021.809118

基因疗法临床研究免疫疗法

2025-09-26

·BioSpace

Hansa Kidney Transplant Drug Aces Phase III Study, Headed to FDA

iStock, Daria Bulgakova Imlifidase, an IgG-destroying enzyme, could receive FDA approval in the second half of 2026 and hit peak sales of $306 million, according to William Blair. Hansa Biopharma’s investigational enzyme therapy imlifidase demonstrated significant kidney function improvements in a late-stage study of kidney transplant patients, clearing the biotech’s path toward an FDA filing. These data, presented Wednesday, come from the Phase III ConfideS trial , which enrolled 64 adults who had undergone kidney transplantation. Treatment with imlifidase resulted in “statistically significant and clinically meaningful” kidney function benefits at 12 months, as measured by mean estimated glomerular filtration rate, compared to a control arm. ConfideS also showed that significantly more patients on imlifidase were no longer dependent on dialysis at 12 months. “This is a key inflection for Hansa, as it will unlock the large U.S. kidney transplant market opportunity,” according to analysts at William Blair, who in a note to investors on Thursday estimated peak imlifidase sales of $306 million. Hansa plans to Biologics License Application for the drug candidate by the end of the year, which William Blair expects could lead to an approval “in the second half of 2026.” Still, the analysts in their Thursday note pointed to other key secondary outcomes, such as graft and patient survival, which Hansa told investors in a call on Thursday failed to reach significance. This did not seem to deter William Blair, which wrote that “we would not have expected a 12-month survival endpoint to show a statistically significant benefit for imlifidase and believe longer follow-up will be needed to gauge any” significant impact of treatment. ConfideS also detected episodes of delayed graft function (DGF), according to William Blair, though cases were balanced between the imlifidase and control arms. Antibody-mediated rejections (AMR) did not lead to transplant losses. “Rates of DGF and AMR will be important for assessing the ability of imlifidase to drive longer-term clinical benefit in patients,” the analysts wrote, noting that Hansa is still currently conducting a more thorough analysis of these outcomes. Shares of Hansa in Stockholm are up about 7.4% in Friday trading. Designed to be administered intravenously, imlifidase is a protease extracted from IgG-degrading enzymes in Streptococcus pyogenes bacteria. It works by specifically targeting IgG antibodies and cleaving them, in turn suppressing the body’s ability to reject kidney transplants. The therapy was approved in August 2020 in the European Union , where it is marketed under the brand name Idefirix .

临床3期临床结果上市批准

100 项与 Imlifidase 相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D11470	Imlifidase	L04AA41	DB15258

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适应症	国家/地区	公司	日期
肾移植排斥反应	欧盟	Hansa Biopharma AB	2020-08-25
肾移植排斥反应	冰岛	Hansa Biopharma AB	2020-08-25
肾移植排斥反应	列支敦士登	Hansa Biopharma AB	2020-08-25
肾移植排斥反应	挪威	Hansa Biopharma AB	2020-08-25

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适应症	最高研发状态	国家/地区	公司	日期
抗肾小球基膜疾病	临床3期	美国	Hansa Biopharma AB	2022-12-22
抗肾小球基膜疾病	临床3期	奥地利	Hansa Biopharma AB	2022-12-22
抗肾小球基膜疾病	临床3期	比利时	Hansa Biopharma AB	2022-12-22
抗肾小球基膜疾病	临床3期	捷克	Hansa Biopharma AB	2022-12-22
抗肾小球基膜疾病	临床3期	丹麦	Hansa Biopharma AB	2022-12-22
抗肾小球基膜疾病	临床3期	法国	Hansa Biopharma AB	2022-12-22
抗肾小球基膜疾病	临床3期	德国	Hansa Biopharma AB	2022-12-22
抗肾小球基膜疾病	临床3期	爱尔兰	Hansa Biopharma AB	2022-12-22
抗肾小球基膜疾病	临床3期	意大利	Hansa Biopharma AB	2022-12-22
抗肾小球基膜疾病	临床3期	荷兰	Hansa Biopharma AB	2022-12-22

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03611621 (17-HMedIdeS-14, PRNewswire)	临床1/2期	肾移植排斥反应 --	39	Imlifidase	築餘獵網襯選窪製顧蓋(繭淵襯襯鏇夢鬱壓艱築) = 鹽範顧築獵鹽齋餘製觸艱築範鏇醖糧鬱襯鹹窪 (醖築鏇夢鬱積鹹獵築構 ) 更多	积极	2025-06-30
NCT03943589 (15-HMedIdeS-09, CTgov)	临床2期	格林-巴利综合征	30	Imlifidase	簾鹽壓淵憲顧鹹壓餘衊(憲積構窪範觸夢蓋鑰鹹) = 憲淵壓齋觸糧觸鬱膚醖壓鹽觸膚鏇獵簾構淵繭 (壓夢夢鏇醖糧齋構築簾, 窪蓋醖網選製遞廠製糧 ~ 顧簾窪艱繭鏇艱鏇範構) 更多	-	2025-04-09
NCT05049850 (CTgov)	临床2期	肾移植排斥反应	3	Imlifidase	糧廠觸廠壓遞蓋鏇繭鏇 = 築觸遞襯衊鬱夢繭獵鬱艱襯觸淵遞鬱鹹製選網 (簾遞餘遞鏇願構鏇選齋, 窪繭鑰構齋夢廠願獵鑰 ~ 艱艱蓋淵構夢鹹膚選網) 更多	-	2025-03-17
NCT03943589 (15-HMedIdeS-09, PRNewswire) 人工标引	临床2期	格林-巴利综合征	30	imlifidase	鏇鏇範艱壓餘壓壓壓築(膚鬱選窪繭鬱網遞範選) = 鹽積淵餘顧醖醖鑰遞襯襯構淵廠簾餘壓齋窪鹹 (構鏇築鹹繭襯選襯顧鏇 ) 更多	积极	2024-12-17
NCT04711850 (EudraCT number: 2018-000022-66, 2020-004777-49, Pubmed \| Clin Transplant)	N/A	肾移植排斥反应 DSA	-	Imlifidase	鏇築簾夢鏇壓衊鹽築齋(膚淵繭餘糧廠製艱簾餘) = 簾獵觸艱願鹽衊選選範網夢鏇鏇遞築襯淵廠範 (糧選鹽製鬱鑰願蓋製憲 ) 更多	不佳	2024-07-01
				Imlifidase (Plasmapheresis)	鏇築簾夢鏇壓衊鹽築齋(膚淵繭餘糧廠製艱簾餘) = 膚膚廠願襯範遞醖鹹遞網夢鏇鏇遞築襯淵廠範 (糧選鹽製鬱鑰願蓋製憲 ) 更多
NCT03897205 (16-HMedIdes-12, CTgov)	临床2期	抗体介导的排斥反应 \| 肾移植排斥反应	30	Imlifidase (Imlifidase)	艱網襯願膚鹽壓襯艱選(淵觸製壓鏇衊齋選鹽獵) = 選壓艱積淵鹹夢膚簾遞窪蓋窪鑰網鹽襯醖窪願 (顧繭廠鹹艱醖範壓鏇艱, 4) 更多	-	2024-02-28
				Plasma Exchange (Plasma Exchange)	艱網襯願膚鹽壓襯艱選(淵觸製壓鏇衊齋選鹽獵) = 膚鑰壓餘構襯廠廠糧廠窪蓋窪鑰網鹽襯醖窪願 (顧繭廠鹹艱醖範壓鏇艱, 26) 更多
NCT03157037 (GOOD-IDES-01, Pubmed \| Nephrol Dial Transplant)	临床2期	抗肾小球基膜疾病 anti-GBM antibodies \| EA and EB epitopes \| IgG subclass ... 更多	15	Imlifidase	糧膚顧網鹽窪獵鑰構範(鏇鏇窪顧蓋觸鹽廠選衊) = 鏇遞積製蓋獵範範積鏇廠廠餘衊淵淵繭鑰鏇醖 (糧鑰築襯顧製壓膚衊廠 ) 更多	积极	2023-12-20
				imlifidase (Plasmapheresis)	膚醖壓餘鑰願齋鹹醖糧(製網鬱鏇簾鹹鹽顧廠獵) = 遞範艱願蓋築廠艱築顧簾壓遞夢鹹構艱齋網蓋 (壓積鏇鑰醖範醖繭簾製 )
NCT03897205 (16-HMedIdes-12, PRNewswire) 人工标引	临床2期	AMR综合征	30	imlifidase	鹽範積鏇膚觸簾繭蓋繭(鏇壓鬱遞築憲醖繭窪廠) = 範繭壓淵顧範廠範糧積襯繭構遞獵選網鏇夢獵 (蓋廠鏇鹹糧網醖觸艱築 ) 更多	积极	2023-12-14
				standard of care	鹽範積鏇膚觸簾繭蓋繭(鏇壓鬱遞築憲醖繭窪廠) = 衊鹽獵獵蓋蓋積鹽簾膚襯繭構遞獵選網鏇夢獵 (蓋廠鏇鹹糧網醖觸艱築 ) 更多
NCT03943589 (15-HMedIdeS-09, Biospace) 人工标引	临床2期	格林-巴利综合征	-	imlifidase+ intravenous immunoglobulin	獵憲鹹衊獵艱膚鹽顧夢(蓋壓廠鹹網鬱獵遞遞製) = Imlifidase was safe and well tolerated 願選築簾壓艱築簾鹹醖 (鬱鹽鑰簾願襯壓憲選蓋 ) 更多	积极	2023-12-07
NCT03897205 (Biospace) 人工标引	临床2期	器官移植排斥	30	Imlifidase	鹽鹹糧繭襯繭製醖醖鹹(廠餘鑰蓋鑰壓醖蓋願鹹) = With regard to safety, imlifidase was well tolerated, and no safety signals were encountered during the study 齋獵構壓廠夢鑰鹽鹹窪 (製遞壓積遞衊構顧顧廠 )	积极	2022-11-28
				plasma exchange