An Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Activity of Zilucoplan in Pediatric Study Participants With Acetylcholine Receptor Antibody Positive Generalized Myasthenia Gravis

The purpose of this study is to assess the long-term safety and tolerability of an additional 52 weeks of Zilucoplan treatment administered by subcutaneous injection once daily in pediatric study participants

Start Date28 Oct 2024

Sponsor / Collaborator

UCB Biopharma SRL

NCT06055959 / RecruitingPhase 2/3

A Multicenter Open-Label, Uncontrolled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Activity of Zilucoplan in Pediatric Study Participants From 2 to Less Than 18 Years of Age With Acetylcholine Receptor Antibody Positive Generalized Myasthenia Gravis

The purpose of this study is to assess the pharmacokinetics, pharmacodynamics, safety, tolerability, immunogenicity and activity of zilucoplan (ZLP) in pediatric study participants with generalized myasthenia gravis (gMG).

Start Date16 Oct 2024

Sponsor / Collaborator

UCB Biopharma SRL

CTIS2023-508287-30-00 / Not yet recruiting

A MULTICENTER, OPEN-LABEL, OUTPATIENT STUDY TO EVALUATE THE SAFE AND EFFECTIVE USE OF A ZILUCOPLAN AUTO INJECTOR COMBINATION PRODUCT FOR SUBCUTANEOUS SELF-ADMINISTRATION BY STUDY PARTICIPANTS WITH GENERALIZED MYASTHENIA GRAVIS - DV0013

Start Date29 Aug 2024

Sponsor / Collaborator

UCB Biopharma SA

100 Clinical Results associated with Zilucoplan

100 Translational Medicine associated with Zilucoplan

100 Patents (Medical) associated with Zilucoplan

Literatures (Medical) associated with Zilucoplan

01 Nov 2024·PEDIATRIC DRUGS

Targeted Treatments for Myasthenia Gravis in Children and Adolescents

Review

Author: Lim, Ming J ; Famili, Dennis T ; Jungbluth, Heinz ; Ramdas, Sithara ; Vanegas, Maria I ; Painho, Teresa

Myasthenia gravis (MG) is an antibody-mediated disorder of the neuromuscular junction affecting children and adults. MG is a treatable condition with most patients requiring immunosuppression for disease control and/or remission. Juvenile myasthenia gravis (JMG) is rare in comparison with adult-onset MG but given the same underlying pathophysiology, treatment strategies are similar to those in adults. Until recently, there were only a few randomised controlled trials (RCTs) for MG treatments in adults and none in children, and management strategies were primarily based on expert consensus. In addition, treatment options for refractory MG cases have been severely limited, resulting in poor long-term quality of life in such patients due to the significant disease burden. Recently, there have been several RCTs focussing on novel therapeutic strategies with potentially promising outcomes, suggesting a change in MG management over the coming years and access to more effective and faster-acting drugs for MG patients. This paper will review current and new MG treatments including efgartigimod, eculizumab, rozanolixizumab, ravulizumab, and zilucoplan, with a focus on juvenile myasthenia gravis.

02 Oct 2024·Expert Review of Medical Devices

Usability of the zilucoplan prefilled syringe for the treatment of generalized myasthenia gravis: insights from a human factors validation study

Article

Author: Ashraghi, Mohammad ; Domanska, Barbara ; Boroojerdi, Babak ; Ruzhansky, Katherine ; Franchini, Alessandra ; Leite, Maria Isabel

BACKGROUND:

Generalized myasthenia gravis (gMG) is a chronic, autoimmune neuromuscular disease, often accompanied by high treatment burden. The objective of this usability study was to validate that the zilucoplan prefilled syringe (PFS) can be used safely and effectively.

METHODS:

The study recruited 75 participants representing five distinct user groups (injection-naïve gMG patients, injection-experienced gMG patients, injection-naïve caregivers, injection-experienced caregivers, and healthcare professionals), who each simulated an injection without being directed to use the instructions for use (IFU). Participants were then asked to repeat the process as directed by the IFU. Participants were assessed and use errors identified using performance-based criteria.

RESULTS:

73/75 (97.3%) participants were able to safely administer the dose of medication during the first simulated use, with or without the IFU. When utilizing the IFU, all 75 (100.0%) participants were able to administer the medication. The rate of use errors was low, with pass rates for observation-based tasks ranging from 85.3% to 100.0%, and in general, after participants were instructed to refer to the IFU, the rate of use errors was reduced.

CONCLUSIONS:

This human factors study demonstrated that the zilucoplan PFS is safe and effective for intended users, including patients with gMG and their caregivers.

01 May 2024·International journal of laboratory hematology

Complement inhibition in paroxysmal nocturnal hemoglobinuria: From biology to therapy

Review

Author: Fattizzo, Bruno ; Versino, Francesco

Abstract:

Complement inhibitors are the mainstay of paroxysmal nocturnal hemoglobinuria (PNH) treatment. The anti‐C5 monoclonal antibody eculizumab was the first treatment to improve hemolysis, thrombotic risk, and survival in PNH although at the price of a life‐long intravenous fortnightly drug. Additionally, suboptimal response may occur in up to 2/3 of patients with persistent anemia due to incomplete control of intravascular hemolysis, development of upstream C3‐mediated extravascular hemolysis (EVH), or concomitant bone marrow failure. Ravulizumab, a longer half‐life anti‐C5 developed from eculizumab, administered every 8 weeks, improved patient convenience, and reduced pharmacokinetic breakthrough hemolysis (BTH) by establishing more stable anti‐C5 concentrations. More recently, several other anti‐C5 compounds (crovalimab, pozelimab, tesidolumab, cemdisiran, zilucoplan, and coversin) are on study in clinical trials. Upstream inhibition of complement cascade was also explored with the anti‐C3 pegcetacoplan, and with the alternative pathway inhibitors iptacopan (anti‐factor B) and danicopan (anti‐factor D). These drugs efficiently target EVH and are able to improve anemia and transfusion need in suboptimal responders to anti‐C5. The route and schedule of administration (twice weekly subcutaneously for pegcetacoplan and twice or thrice oral daily dosing for iptacopan and danicopan, respectively) are very convenient but pose novel issues regarding adherence. Additionally, both anti‐C5 and upstream inhibitors do not resolve the unmet need of pharmacodynamic BTH events due to complement amplifying conditions such as infections, traumas, and surgery. In this review, we will recapitulate PNH physiopathology, clinical presentation, and diagnosis and describe available and developing drugs that will lead to a precision medicine approach for this rare though heterogenous disease.

News (Medical) associated with Zilucoplan

11 Oct 2024

·www.prnewswire.com

UCB showcases new data for gMG management at the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting and Myasthenia Gravis Foundation of America (MGFA) Scientific Session

UCB will contribute 14 presentations, including an oral presentation, selected to feature across the AANEM and MGFA meeting, emphasizing UCB's leadership in neuromuscular research Presentations showcase new data for UCB's gMG treatments, including post hoc analyses highlighting the long-term safety and efficacy of ZILBRYSQ® (zilucoplan)1 and RYSTIGGO® (rozanolixizumab-noli) 2 BRUSSELS, Oct. 11, 2024 /PRNewswire/ -- UCB (Euronext Brussels: UCB), a global biopharmaceutical company, today announced that it will be presenting results from across its portfolio in generalized myasthenia gravis (gMG) at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) annual meeting and the Myasthenia Gravis Foundation of America (MGFA) Scientific Session taking place October 15—18, 2024 at the Savannah Convention Center in Savannah, Georgia, U.S. A total of 14 abstracts, including one oral presentation, will feature data from studies of UCB's recently approved medicines for the treatment of gMG, RYSTIGGO® and ZILBRYSQ®, along with findings from real-world studies of clinical outcomes and patient experience in gMG. "At UCB, we are committed to transforming the lives of those living with generalized myasthenia gravis through ongoing innovation and comprehensive clinical research," commented Manuela Maronati, Global Asset Head, Neuroimmunology & Rare. "Our presentations at the 2024 AANEM Annual Meeting and MGFA Scientific Session underscore our dedication to advancing understanding and treatment of this challenging condition. We are particularly excited to share insights from our RAISE-XT and MycarinG studies, which reflect significant progress in the management of generalized myasthenia gravis." Key UCB scientific and real-world data to be presented at AANEM and the MGFA Scientific Session include: An oral presentation focusing on UCB's innovative work on enhancing global education standards for myasthenia gravis.3 Phase 3b study results on switching to subcutaneous zilucoplan from IV complement component 5 inhibitors in myasthenia gravis.4 Data from the RAISE-XT trial for zilucoplan - including an interim analysis of long-term safety and efficacy over a period of up to 120 weeks, compliance to daily self-administered subcutaneous zilucoplan, and a post-hoc analysis of corticosteroid sparing and non-steroidal immunosuppressant therapy changes up to 120 weeks - offering new insights into the management potential for generalized myasthenia gravis in a clinical setting.5,6,7 For rozanolixizumab, post hoc analyses from the Phase 3 MycarinG trial in patients with generalized myasthenia gravis describe the impact of treatment on specific muscle group weaknesses, evaluate rozanolixizumab in those aged 65 years and older, and highlight its use for individualized treatment regimens.8,9,10 UCB will also host an industry-sponsored therapeutic update session on an expert-led discussion on generalized myasthenia gravis treatment choices on October 16, 2024. "At this year's AANEM Annual Meeting and MGFA Scientific Session, we are proud to share data from UCB's innovative work, which is advancing the standard of education for generalized myasthenia gravis globally. This program not only underscores our dedication to empowering healthcare professionals with knowledge and tools but also highlights our ongoing commitment to addressing the complex challenges faced by the MG community," commented Emmanuel Caeymaex, Executive Vice President, Head of Patient Impact, UCB. UCB presentations during AANEM and MGFA 2024 Additionally, for registered healthcare professionals, UCB has arranged a program of sponsored scientific and therapeutic updates. Visit us at our booth for more information. UCB For further information, contact UCB: U.S. Rare Disease Communications Daphne Teo T +1 (770) 880-7655 [email protected] Global Communications Nick Francis T: +44 7769 307745 [email protected] Corporate Communications, Media Relations Laurent Schots T +32.2.559.92.64 [email protected] Investor Relations Antje Witte T +32.2.559.94.14 [email protected] IMPORTANT SAFETY INFORMATION ABOUT RYSTIGGO® (rozanolixizumab-noli) in the US2 INDICATION: RYSTIGGO (rozanolixizumab-noli) is a neonatal Fc receptor blocker indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Infections: RYSTIGGO may increase the risk of infection. Delay RYSTIGGO administration in patients with an active infection until the infection is resolved. During treatment with RYSTIGGO, monitor for clinical signs and symptoms of infection. If serious infection occurs, administer appropriate treatment and consider withholding RYSTIGGO until the infection has resolved. Immunization Immunization with vaccines during RYSTIGGO treatment has not been studied. The safety of immunization with live or live-attenuated vaccines and the response to immunization with any vaccine are unknown. Because RYSTIGGO causes a reduction in IgG levels, vaccination with live-attenuated or live vaccines is not recommended during treatment with RYSTIGGO. Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with RYSTIGGO. Aseptic Meningitis: Serious adverse reactions of aseptic meningitis (also called drug-induced aseptic meningitis) have been reported in patients treated with RYSTIGGO. If symptoms consistent with aseptic meningitis develop, diagnostic workup and treatment should be initiated according to the standard of care. Hypersensitivity Reactions: Hypersensitivity reactions, including angioedema and rash, were observed in patients treated with RYSTIGGO. Management of hypersensitivity reactions depends on the type and severity of the reaction. Monitor patients during treatment with RYSTIGGO and for 15 minutes after for clinical signs and symptoms of hypersensitivity reactions. If a reaction occurs, institute appropriate measures if needed. ADVERSE REACTIONS In a placebo-controlled study, the most common adverse reactions (reported in at least 10% of RYSTIGGO-treated patients) were headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea. Serious infections were reported in 4% of patients treated with RYSTIGGO. Three fatal cases of pneumonia were identified, caused by COVID-19 infection in two patients and an unknown pathogen in one patient. Six cases of infections led to discontinuation of RYSTIGGO. Please see the full Prescribing Information for additional Important Safety Information. IMPORTANT SAFETY INFORMATION ABOUT ZILBRYSQ® (zilucoplan) in the US1 INDICATION: ZILBRYSQ is a complement inhibitor indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. IMPORTANT SAFETY INFORMATION INCLUDING BOXED WARNING WARNING: SERIOUS MENINGOCOCCAL INFECTIONS Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors ; ZILBRYSQ is a complement inhibitor. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update meningococcal vaccination (for serogroups A, C, W, and Y, and serogroup B) at least 2 weeks prior to administering the first dose of ZILBRYSQ, unless the risk of delaying therapy outweighs the risk of developing a meningococcal infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccinations in patients receiving a complement inhibitor. Persons receiving ZILBRYSQ are at increased risk for invasive disease caused by N. meningitidis, even if they develop antibodies following vaccination. Monitor patients for signs of meningococcal infections and evaluate immediately if infection is suspected. Because of the risk of serious meningococcal infections, ZILBRYSQ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ZILBRYSQ REMS. CONTRAINDICATIONS ZILBRYSQ is contraindicated in patients with unresolved Neisseria meningitidis infection. WARNINGS AND PRECAUTIONS Serious Meningococcal Infections Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors; ZILBRYSQ is a complement inhibitor. The use of ZILBRYSQ increases a patient's susceptibility to serious and life-threatening meningococcal infections (septicemia and/or meningitis) caused by any serogroup, including non-groupable strains. Complete or update meningococcal vaccination (for both serogroups A, C, W, and Y [MenACWY] and serogroup B [MenB]) at least 2 weeks prior to administering the first dose of ZILBRYSQ, according to current ACIP recommendations for meningococcal vaccinations in patients receiving a complement inhibitor. If urgent ZILBRYSQ therapy is indicated in a patient who is not up to date with both MenACWY and MenB vaccines according to ACIP recommendations, administer meningococcal vaccine(s) as soon as possible and provide the patient with antibacterial drug prophylaxis. Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected. Withhold administration of ZILBRYSQ in patients who are undergoing treatment for meningococcal infection until the infection is resolved. ZILBRYSQ REMS Due to the risk of meningococcal infections, ZILBRYSQ is available only through a restricted program under a REMS called ZILBRYSQ REMS. Under the ZILBRYSQ REMS, prescribers must enroll in the program. Prescribers must counsel patients about the risk of meningococcal infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccines. Additional information on the REMS requirements is available at or 1-877-414-8353. Other Infections ZILBRYSQ blocks terminal complement activation; therefore, patients may have increased susceptibility to infections, especially with encapsulated bacteria, such as infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP guidelines. Persons receiving ZILBRYSQ are at increased risk for infections due to these bacteria, even after vaccination. Pancreatitis And Other Pancreatic Conditions Pancreatitis and pancreatic cysts have been reported in patients treated with ZILBRYSQ. Patients should be informed of this risk before starting ZILBRYSQ. Obtain lipase and amylase levels at baseline before starting treatment with ZILBRYSQ. Discontinue ZILBRYSQ in patients with suspected pancreatitis and initiate appropriate management until pancreatitis is ruled out or has resolved. ADVERSE REACTIONS In a placebo-controlled study, the most common adverse reactions (reported in at least 10% of gMG patients treated with ZILBRYSQ) were injection site reactions, upper respiratory tract infections, and diarrhea. Please see the full Prescribing Information for additional Important Safety Information. About UCB UCB, Brussels, Belgium () is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With approximately 9 000 people in approximately 40 countries, the company generated revenue of € 5.3 billion in 2023. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCBUSA Forward looking statements This press release may contain forward-looking statements including, without limitation, statements containing the words "believes", "anticipates", "expects", "intends", "plans", "seeks", "estimates", "may", "will", "continue" and similar expressions. These forward-looking statements are based on current plans, estimates and beliefs of management. All statements, other than statements of historical facts, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, arbitration, political, regulatory or clinical results or practices and other such estimates and results. By their nature, such forward-looking statements are not guarantees of future performance and are subject to known and unknown risks, uncertainties and assumptions which might cause the actual results, financial condition, performance or achievements of UCB, or industry results, to differ materially from those that may be expressed or implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: the global spread and impact of COVID-19, changes in general economic, business and competitive conditions, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms or within expected timing, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, product liability claims, challenges to patent protection for products or product candidates, competition from other products including biosimilars, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in tax laws or the administration of such laws, and hiring and retention of its employees. There is no guarantee that new product candidates will be discovered or identified in the pipeline, will progress to product approval or that new indications for existing products will be developed and approved. Movement from concept to commercial product is uncertain; preclinical results do not guarantee safety and efficacy of product candidates in humans. So far, the complexity of the human body cannot be reproduced in computer models, cell culture systems or animal models. The length of the timing to complete clinical trials and to get regulatory approval for product marketing has varied in the past and UCB expects similar unpredictability going forward. Products or potential products, which are the subject of partnerships, joint ventures or licensing collaborations may be subject to differences disputes between the partners or may prove to be not as safe, effective or commercially successful as UCB may have believed at the start of such partnership. UCB's efforts to acquire other products or companies and to integrate the operations of such acquired companies may not be as successful as UCB may have believed at the moment of acquisition. Also, UCB or others could discover safety, side effects or manufacturing problems with its products and/or devices after they are marketed. The discovery of significant problems with a product similar to one of UCB's products that implicate an entire class of products may have a material adverse effect on sales of the entire class of affected products. Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment, including pricing pressure, political and public scrutiny, customer and prescriber patterns or practices, and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement activities and outcomes. Finally, a breakdown, cyberattack or information security breach could compromise the confidentiality, integrity and availability of UCB's data and systems. Given these uncertainties, you should not place undue reliance on any of such forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labelling in any market, or at any particular time, nor can there be any guarantee that such products will be or will continue to be commercially successful in the future. UCB is providing this information, including forward-looking statements, only as of the date of this press release and it does not reflect any potential impact from the evolving COVID-19 pandemic, unless indicated otherwise. UCB is following the worldwide developments diligently to assess the financial significance of this pandemic to UCB. UCB expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report or reflect any change in its forward-looking statements with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless such statement is required pursuant to applicable laws and regulations. Additionally, information contained in this document shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any offer, solicitation or sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such jurisdiction. References 1 ZILBRYSQ® US PI. . (Accessed: October 2024). 2 RYSTIGGO® US PI. . (Accessed: October 2024). 3 Howard J, et al. Developing needs-driven medical education for healthcare professionals in myasthenia gravis. Poster presented at: The American Academy of Neurology and Electrodiagnostic Medicine Annual Meeting (AANEM); 2024, October 15-18; Georgia, USA. 4 Freimer M, et al. Switching to subcutaneous zilucoplan from IV complement component 5 inhibitors in myasthenia gravis: A Phase 3b study. Poster presented at: The American Academy of Neurology and Electrodiagnostic Medicine Annual Meeting (AANEM); 2024, October 15-18; Georgia, USA. 5 Howard J, et al. Long-term safety and efficacy of zilucoplan in generalized myasthenia gravis: 120-week interim analysis of RAISE-XT. Poster presented at: The American Academy of Neurology and Electrodiagnostic Medicine Annual Meeting (AANEM); 2024, October 15-18; Georgia, USA. 6 Ruzhansky K, et al. Compliance to daily self-administered subcutaneous zilucoplan in patients with generalized myasthenia gravis: a post hoc analysis of the RAISE-XT study. Poster presented at: The American Academy of Neurology and Electrodiagnostic Medicine Annual Meeting (AANEM); 2024, October 15-18; Georgia, USA. 7 Freimer M, et al. Corticosteroid dose tapering during treatment with zilucoplan in patients with generalized myasthenia gravis: 120-week follow-up of RAISE-XT. Poster presented at: The American Academy of Neurology and Electrodiagnostic Medicine Annual Meeting (AANEM); 2024, October 15-18; Georgia, USA. 8 Pascuzzi R, et al. Effect of rozanolixizumab on myasthenia gravis–specific outcome subdomain scores: post hoc analyses from the phase 3 MycarinG study. Poster presented at: The American Academy of Neurology and Electrodiagnostic Medicine Annual Meeting (AANEM); 2024, October 15-18; Georgia, USA. 9 Vu T, et al. Rozanolixizumab in patients aged ≥65 years with generalized myasthenia gravis: a post hoc analysis of the Phase 3 MycarinG study. Poster presented at: The American Academy of Neurology and Electrodiagnostic Medicine Annual Meeting (AANEM); 2024, October 15-18; Georgia, USA. 10 Ali A. Habib, et al. Rozanolixizumab treatment patterns in patients with generalized myasthenia gravis: post hoc analysis. Poster presented at: The American Academy of Neurology and Electrodiagnostic Medicine Annual Meeting (AANEM); 2024, October 15-18; Georgia, USA. RYSTIGGO® and ZILBRYSQ® are registered trademarks of the UCB Group of Companies. ©2024 UCB, Inc., Smyrna, GA 30080. All rights reserved. US-RZ-2400542 SOURCE UCB WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3

23 Sep 2024

·www.fiercepharma.com

UCB rapidly bolsters blockbuster potential for Bimzelx with 3 new FDA approvals

The three approvals add up to four indications for UCB's Bimzelx in less than a year. Less than a year after snagging its first FDA approval in psoriasis, UCB’s blockbuster hopeful Bimzelx has picked up three more indications to add to its growing resume of inflammatory disease treatment.The FDA cleared Bimzelx to treat adults with active psoriatic arthritis (PsA), active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation, and active ankylosing spondylitis (AS). The med is the first IL-17A/F inhibitor approved to treat the three indications, UCB noted in a press release. “In psoriatic arthritis and across the spectrum of axSpA, clinical study results and real-world experience outside the U.S. have highlighted that Bimzelx can help patients achieve high thresholds of clinical response that are rapid in onset and sustained up to two years,” the company’s chief commercial officer, Emmanual Caeymaex, said in the release.The three new nods stand to bolster the company’s stated peak sales expectations of at least 4 billion euros ($4.4 billion) for Bimzelx. Even still, there’s more to come for the drug. The FDA accepted UCB’s bid for another use, this time in hidradenitis suppurativa, back in April.As of July, the therapy has reached more than 35,000 patients globally, CEO Jean-Christophe Tellier commented in the company’s half-year financial report. During the period, Bimzelx picked up 215 million euros ($239 million) in sales, with the bulk coming from Europe. Tellier gave Bimzelx the title of a "best-in-disease" profile with a "tremendous value proposition" in an interview last year. While the FDA initially delayed an approval in 2021 based on manufacturing issues, regulators in Europe cleared the med in 2022 and have since approved it in all four of its follow-up indications, including in hidradenitis suppurativa. Despite the hold-up, Bimzelx’s launch in psoriasis has been “the strongest” in the U.S. market against all biologics based on prescriptions, UCB’s head of U.S. immunology Camile Lee said in an interview with Fierce Pharma. Lee also highlighted the drug’s rapid onset of treatment effect and sustained benefits over two years as demonstrated by a 2021 study.“What we’re doing with Bimzelx is bringing higher standards of care so that the patients can live life with a disease versus their disease living their life for them,” Lee added.The company expects its full-year revenue to come in near 5.7 billion euros ($6.3 billion). Along with Bimzelx, the sales growth should be driven by ongoing global launches of its recently approved generalized myasthenia gravis meds Rystiggo and Zilbrysq, the drugmaker said in an earnings call earlier this year.

Drug ApprovalBiosimilar

16 Sep 2024

·www.biospace.com

The HEALEY Platform Trial: Quick Failures and New Hope for ALS

iStock/ higyou Launched in 2020 to more quickly bring to market an effective medicine for amyotrophic lateral sclerosis, the HEALEY Platform Trial has generated disappointing results for many but also continuing programs from Clene and Prilenia. Clinical wins have been few and far between for the HEALEY ALS Platform Trial . A heterogeneous patient population and delays have posed challenges, with several biotechs discontinuing programs based on underwhelming results. But optimism persists among the trial’s leaders and early participants, with two companies, Clene Nanomedicine and Prilenia Therapeutics, moving their investigational amyotrophic lateral sclerosis (ALS) treatments forward. The first seed for an ALS platform trial was planted when Massachusetts General Hospital’s Merit Cudkowicz read an article on master platform trials by former FDA Principal Deputy Commissioner Janet Woodcock. “I read that one and thought it might be appropriate for ALS,” Cudkowicz told BioSpace . Then, along came Sean Healey, a prominent American businessman who had recently been diagnosed with ALS, with an attractive opportunity. He said, “I might not save myself from this illness, but I want to make a difference. Give me a proposal,” Cudkowicz recalled. So she and her team worked around the clock, ultimately pitching the platform trial, and “[Healey] loved it. He just got it right away, that it was efficient and good for patients.” Healey, in partnership with his global asset management firm, Affiliated Managers Group (AMG), donated $40 million to launch the Sean M. Healey & AMG Center for ALS at Mass General, and set in motion a new chapter in ALS research. Cudkowicz serves as the center’s director. Biopharma quickly jumped on board with the platform trial, with dozens of companies—in addition to Clene and Prilenia, UCB, Biohaven Pharmaceutical and Seelos Therapeutics—vying to be a part of it. Fast forward four years and none of these drugs has hit the trial’s primary endpoints. But Clene CEO Rob Etherington said that doesn’t reflect a failure of the study itself. The HEALEY trial was designed to “fast fail” assets that don’t have utility, he explained, “and it worked in that respect, for a few of the regimens.” Indeed, Cudkowicz noted that Biohaven, which ultimately opted against moving forward with the program, also viewed the trial as a success because “they got a quick answer, a clear answer.” Biohaven did not respond to BioSpace ’s request for comment. But perhaps most notably, Clene and Prilenia showed positive data on secondary endpoints that prompted those companies to progress their candidates, Cudkowicz said. “So, I really actually view that as a success.” The First Five To select the initial round of participants in the trial, Cudkowicz and her team decided to host a competition. She noted that many aspiring platform trials seemed to be stuck at the funding stage and believed a call for proposals would speed up the process. The prize: entry into the Healey ALS Platform Trial, where some costs for the first companies would be covered. The team received 30 proposals from all over the world. Cudkowicz and her colleagues assessed each therapy based on clinical potential, mechanism of action, and diversity of approach. “We did want to pick drugs with different targets for the first five,” Cudkowicz said. Finally, they selected five programs. UBC’s zilucoplan inhibits complement component 5, the dysregulation of which is implicated in ALS, while Biohaven’s verdiperstat blocks the enzyme that reduces oxidative stress and neuroinflammation. Clene’s CNM-Au8, by contrast, is an oral, liquid suspension of gold nanocrystals designed to improve the survival, function, and communication of nerve cells. Prilenia’s pridopidine is also a neuroprotective agent, and Implicit Bioscience’s IC14 is an anti-CD14 monoclonal antibody devised to regulate the pathogenic inflammatory responses to infection and injury. Of these, Clene and Prilenia fared the best. Although both companies’ assets missed their primary endpoints, positive biomarker data and benefit to a subgroup of patients in Prilenia’s case supported moving the programs forward. With Prilenia’s candidate, a subgroup of patients with early-stage ALS who were rapidly declining had “substantially less decline” in ALS Functional Rating Scale-Revised (ALSFRS-R) total score compared to placebo. The company has stated plans to launch a Phase III trial. Meanwhile, Clene has a briefing book in front of the FDA based on HEALEY data and additional biomarker results gleaned from the RESCUE-ALS trial and survival data from ongoing compassionate use protocols. While the agency originally said the data were insufficient to support a new drug application, Clene has since submitted more information, including mechanistic and ALS-specific biomarkers and data on a super-responder group, which Etherington said is now under review. Clene also gathered promising survival and biomarker data from its arm of the HEALEY study. Treatment with CNM-Au8 for up to 133 weeks decreased the risk of death by 49% compared to PRO-ACT database–matched placebo, according to Clene, while also reducing levels of neurofilament light chain (NfL), which is gaining ground as a predictor of clinical outcomes in neurodegenerative diseases. “Without the survival secondary endpoint win and the exploratory endpoint win and the neurofilament biomarker win that HEALEY gave Clene, we’d be in a very different position today,” Etherington said. “We certainly wouldn’t have a briefing book under consideration at the FDA without HEALEY.” The other companies have either shut down their programs or are still determining next steps. Implicit never moved forward to the design phase. UCB’s arm of the trial was stopped early after an interim analysis demonstrated futility, according to a Massachusetts General press release . Meanwhile, Biohaven’s verdiperstat failed to statistically differentiate from placebo, and the drug is no longer listed in the company’s pipeline . Seelos joined after Implicit departed and got mixed results. The company stated in a March press release that while its drug trehalose failed to meet statistical significance in the primary and secondary endpoint in the HEALEY study, it showed a “potential signal of efficacy” in a subgroup of patients not taking Amylyx’s Relyvrio, which was given to some trial participants after its approval in September 2022 . And the HEALEY trial marches on. In July 2022, Calico Life Sciences signed on to test ABBV-CLS-7262, and Denali Therapeutics announced its participation with DNL343 in December of the same year. Data from these arms of the trial are expected in early 2025. Another company, Australian outfit PharmAust, recently committed to studying its drug monepantel, and Cudkowicz said talks are ongoing with several more companies. Cudkowicz said that no matter what the result of the various arms, “you can learn a lot about [ALS].” Patient- and Business-Centric Platform trials are a fairly new phenomenon, and Cudkowicz shared that she learned a lot from the DIAN Alzheimer’s trial at Washington University. The model offers myriad benefits, including efficiency. While a clinical trial typically takes more than a year to get off the ground, the HEALEY study is a perpetual trial , meaning a new drug regimen can be added in just 30 days. It’s also patient-centric. The use of a shared placebo between all regimens means that more patients receive a potentially efficacious drug. This also means companies have to recruit fewer patients. The fact that some of their costs were covered was a significant benefit for the smaller companies in the HEALEY trial. Prilenia, for example, had six employees at the time it applied to join the trial. “The good news was they paid for the drug, so we didn’t have to raise money for [that],” Hayden told BioSpace . The infrastructure build and support were also partially funded by several foundations, Cudkowicz said. “I’m grateful. Without HEALEY, we would never have done this trial,” Hayden said. “We didn’t have the money.” The companies involved also have access to elite experience in the ALS space. Cudkowicz is widely considered to be the dean of ALS drug development, and both Etherington and Hayden referenced the gravitas associated with the HEALEY trial, which includes 75 research sites. “The advantage of HEALEY is undeniably the fact that you have an easy network of top expert centers . . . so you’re really able to access the top centers in the United States of America,” Etherington told BioSpace . “That is a tremendous advantage for young startup companies to have access to and to be involved with.” Etherington added that acceptance into the trial gave CNM-Au8 credibility “because it really was a testament of others’ stamp of approval that are well respected in the space.” Growing Pains Still, a complex structure with so many moving parts is bound to take time to perfect. Etherington noted that every drug is unique, and “a platform study does not enable an individual drug and its unique aspects of mechanism or side effects or administration to actually make any changes” to the trial’s protocol. For example, each cohort in the HEALEY trial has run for six months. For CNM-Au8, this was too short of a window to prove efficacy, Etherington said. “To have everybody come in and have to fit the framework with no exceptions, that’s a challenge.” Notably, Cudkowicz shared that the team is currently considering amending the protocol based on learnings from the first five regimens. “This includes possibly longer duration of follow up on the randomized controlled trial period to address the possibility that some medications need more time to achieve biological and clinical effects,” she said. Cudkowicz added that a voice app developed by Aural Analytics and used in the first four regimens is “turning out to be a very good digital biomarker. We also did home spirometry (a measure of lung function), which looks pretty much just as good as in clinic.” Another challenge for a trial with multiple centers across the U.S., Etherington said, was an initial delay in receiving data from every center, though Clene is now in possession of the final datasets from the HEALEY trial. Because every regimen starts at a different time, they all finish at different times, slowing down the rate at which results are available. For a company conducting a single study, “all hands are on deck,” Etherington said. By contrast, in a platform trial, “we have to be more ecumenical. We have to share, as it were, the load and the timeline, and we need to recognize that the company’s individual interests need to be subjugated, to some degree, to the whole of the platform study.” Hayden agreed, saying that the HEALEY team was sometimes “overwhelmed” with running what amounts to eight trials, and that there sometimes is “a little frustration in terms of the speed of response, the ability to get statistical analysis done. All of that can be slower than we would like.” Cudkowicz acknowledged that the trial has faced challenges in this regard. “Since the idea of platform trials is efficiency and speed, we want all parts of it to be efficient,” she said. “Some of the structural, operational things that slow down trials in general are still in play in platform trials [and] how trials are started up at academic institutions is still too slow, in my opinion. We have some new initiatives to improve this dramatically for the next several new regimens,” she said in an email. Cudkowicz added that interest in the trial overwhelmed the capacity of some of the trial sites. “There’s high interest in it from the companies, from the patients, but now we’ve gotta do it even faster.” A heterogeneous patient population was another challenge, Hayden said. “The study included essentially everybody with ALS, and that was maybe . . . both positive and negative. The positive was that this gave hope to everybody.” However, ALS has a “very heterogeneous population.” The HEALEY trial included patients with definite, probable and possible ALS, as well as those more than three years out from diagnosis. “We were concerned about that right in the beginning because we knew that all the trials that had been successful in ALS had a different population” that included patients with only definite and probable ALS, and a shorter disease duration, Hayden said. Prilenia ultimately prespecified that it wanted to also study pridopidine in patients with early-stage ALS, diagnosed less than 18 months before the trial’s start, and HEALEY investigators were able to recruit from such a population for the arm of the trial testing the drug. And while pridopidine failed the primary endpoint in the full analysis set, in patients with early ALS, “what we saw is that we had a very wonderful positive effect,” Hayden said. “We delayed progression for the first time ever seen in an ALS trial at eight weeks.”

Phase 3Clinical Result

100 Deals associated with Zilucoplan

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KEGG	Wiki	ATC	Drug Bank
-	Zilucoplan	-	DB15636

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Myasthenia Gravis	JP	UCB Japan Co. Ltd.	25 Sep 2023

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Amyotrophic Lateral Sclerosis	Phase 3	US	Ra Pharmaceuticals, Inc.	29 Jul 2020
COVID-19	Phase 2	BE	UCB Pharma GmbH	22 May 2020
Hypoxic respiratory failure	Phase 2	BE	UCB Pharma GmbH	22 May 2020
Immune-mediated necrotising myopathy	Phase 2	US	Ra Pharmaceuticals, Inc.	07 Nov 2019
Immune-mediated necrotising myopathy	Phase 2	FR	Ra Pharmaceuticals, Inc.	07 Nov 2019
Immune-mediated necrotising myopathy	Phase 2	NL	Ra Pharmaceuticals, Inc.	07 Nov 2019
Immune-mediated necrotising myopathy	Phase 2	GB	Ra Pharmaceuticals, Inc.	07 Nov 2019
Necrotizing myopathy	Phase 2	US	Ra Pharmaceuticals, Inc.	07 Nov 2019
Necrotizing myopathy	Phase 2	FR	Ra Pharmaceuticals, Inc.	07 Nov 2019
Necrotizing myopathy	Phase 2	NL	Ra Pharmaceuticals, Inc.	07 Nov 2019

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04225871 (RAISE-XT, MDA2024) Manual	Phase 3	Myasthenia Gravis acetylcholine receptor autoantibody-positive	200	continued zilucoplan or placebo swtiched to zilucoplan	aepmqcaojn(nhktvnkwqf) = kantebfldt srtunwxemc (uqcpghcpbf ) View more	Positive	03 Mar 2024
				Zilucoplan 0.3 mg/kg	llveaqbtmz(mwdwbdugrq) = bhblajyygk nsxzwcuewv (qelldiuqvt ) View more
NCT04115293 (RAISE, FDA) Manual	Phase 3	Myasthenia Gravis	174	ZILBRYSQ	hmpndyaqkm(pibshdmdyf) = myveovrruj abqjliscjb (acwvvkrthx, -5.28 to -3.50) View more	Positive	17 Oct 2023
				Placebo	hmpndyaqkm(pibshdmdyf) = mphwnfpewn abqjliscjb (acwvvkrthx, -3.17 to -1.43) View more
NCT04382755 (ZILU-COV, CTgov)	Phase 2	Hypoxic respiratory failure \| COVID-19	81	Zilucoplan® (Group A (Active))	trithpqbnu(xiqxuewpll) = czpbnodicx loilvfznwh (lnrkldgrjo, beljhpbmng - eybteaittq) View more	-	14 Sep 2023
				Placebo (Group B (Control))	trithpqbnu(xiqxuewpll) = jnmpmgrjyq loilvfznwh (lnrkldgrjo, fxtrtfcfaf - xxswnwbaxh) View more
NCT04436497 (HEALEY Trial-Zilucoplan Arm, CTgov)	Phase 2/3	Amyotrophic Lateral Sclerosis	162	Zilucoplan (Zilucoplan)	krcocaxnfh(zumffoywlh) = vdqfhazyam ihwwpywtxj (gbkdzgrvpo, kfxijvjtfz - uqueqmvcnk) View more	-	25 Jul 2023
				Matching Placebo (Matching Placebo)	krcocaxnfh(zumffoywlh) = fhhcyqkztb ihwwpywtxj (gbkdzgrvpo, tjdcqlgctl - qfiytanaqf) View more
NCT04225871 (RAISE-XT, AAN2023)	Phase 3	Myasthenia Gravis	199	Zilucoplan 0.3 mg/kg	rdunarymcr(mrtfaiixld) = ykyouufuou peqopatcuq (opuxzvnycz ) View more	Positive	25 Apr 2023
				Placebo-switch	(aukbjoymvd) = mzlvojpjyq sjbkfvdatk (umadhotlrk ) View more
NCT04225871 (RAISE-XT, MDA2023) Manual	Phase 3	Myasthenia Gravis	199	zilucoplan 0.3 mg/kg	zpywtcanaj(tkdistqcoq) = awslifjusw orkwgfzmzh (gvrptawore ) View more	Positive	19 Mar 2023
				zilucoplan 0.3 mg/kg (zilucoplan group)	cbmguufiuc(ichbapwcpq) = rhvnecctzm fvhvhldhtl (nxafrfrzac, -7.44 to -5.15)
NCT04115293 (RAISE, CTgov)	Phase 3	Myasthenia Gravis	174	Placebo	zeiohcotee(qmsbodvboh) = pnnycmrnti bmrkaudhmf (cpilgvykni, ozjxlkoblf - vcigiuhmwq) View more	-	17 Jan 2023
NCT03225287 (CTgov)	Phase 2	Hemoglobinuria, Paroxysmal	19	Eculizumab+Zilucoplan (Zilucoplan-Cohort A (Eculizumab Naïve))	ksbrvxrzmm(ndundprfdf) = itoqgslrsn tibndqbkkk (pvqhstsgzb, faltuamrwu - crksqaexxl) View more	-	27 Oct 2022
				Eculizumab+Zilucoplan (Zilucoplan-Cohort B (Eculizumab Switch))	ksbrvxrzmm(ndundprfdf) = fudggalhlj tibndqbkkk (pvqhstsgzb, jsozbmrwto - nredlzgyxh) View more
NCT04382755 (Pubmed)	Phase 2	COVID-19	81	Zilucoplan + standard of care	ygiskhxfub(vmbaakmvhf) = qywfonxbvs hesbmijodg (txcrryeoca ) View more	Positive	09 Aug 2022
				zilucoplan (Standard of care)	ygiskhxfub(vmbaakmvhf) = rvdjoyweqp hesbmijodg (txcrryeoca ) View more
NCT04025632 (CTgov)	Phase 2	Necrotizing myopathy \| Immune-mediated necrotising myopathy	27	Placebo	dwkwxmnexv(hwpkkjzsyp) = vfvtiifuha irpiimdwsi (szsyvxdlvj, ttktixeivt - jqsadaekcp) View more	-	16 May 2022

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