Copper Histidine

FDA approves first Menkes disease treatmentThe FDA cleared Zycubo (copper histidinate) from Zydus Lifesciences' US subsidiary Sentynl Therapeutics as the first treatment for paediatric patients with Menkes disease, a rare and often fatal inherited disorder of copper deficiency, offering a subcutaneously-administered copper replacement therapy."For the first time, patients have access to an approved therapy, offering hope where no options existed," said Sharvil Patel, managing director of Zydus.The approval was backed by two single-arm trials comparing 66 Zycubo recipients with 17 untreated controls. Results showed that initiating treatment within four weeks of birth cut mortality by 78%, with nearly half surviving beyond six years — some over 12 years — while no untreated patients lived past six; commencing treatment later also delivered meaningful survival gains.The drug, rights of which were gained from Fortress Biotech in 2023, was issued a complete response letter by the US regulator last year, owing to manufacturing site deficiencies.Novartis goes shopping in China for next RLTNovartis signed a worldwide licensing deal with China-based Zonsen PepLib Biotech for a peptide-based radioligand therapy (RLT) asset, agreeing to pay $50 million upfront and unspecified potential future development, regulatory and sales milestones, plus tiered royalties.Novartis will take over global development and commercialisation of the undisclosed programme, which PepLib has advanced internally. "This asset complements our industry-leading efforts to advance promising next-generation RLTs," said Shiva Malek, global head of oncology, Biomedical Research, Novartis, which is anchored by Pluvicto (lutetium Lu 177 vipivotide tetraxetan) for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) and Lutathera (lutetium Lu 177 dotatate) for certain neuroendocrine tumours.Last week, the company revealed plans to build a new RLT manufacturing facility in Winter Park, Florida — its fourth in the US, with a fifth planned as well. The Florida site, expected to come online in 2029, is designed to improve the delivery of highly time-sensitive RLT doses, helping Novartis maintain its target of administering more than 99% of treatments on the planned day.PepLib, which was founded in 2017 and employs more than 200 people across offices in China and New Jersey, said it has built proprietary peptide libraries supporting multiple modalities, including peptide radionuclide conjugates, peptide oligonucleotide conjugates and peptide drug conjugates.Oricell's CAR-T ambitions buoyed by $70M raiseOricell Therapeutics closed a $70 million series C1 financing as it looks to advance its pipeline of CAR-T cell therapies for solid tumours. The funding round was co-led by Beijing Medical and Health Care Industry Investment Fund and Qiming Venture Partners, with other participants including NGS Super, E-Town Capital, Elikon Venture and Talon Capital. The biotech's lead programme, Ori-C101, is an autologous GPC3-targeted CAR-T therapy for advanced hepatocellular carcinoma, which is entering a registrational pivotal trial. Beyond this, Oricell's secreting CAR-T, OriC902, has shown efficacy and durability in ultra-late-line and difficult-to-treat solid tumours, while it is also working on dual-targeted in vivo CAR-T.Oricell — which raised $45 million in 2023 and over $120 million a year earlier — will use the latest proceeds to accelerate its global expansion and clinical development, while strengthening its technological capabilities and preparing for commercialisation.Marea's acromegaly therapy moves to Phase IIMarea Therapeutics reported positive top-line results from its Phase I study of MAR002, a first-in-class monoclonal antibody targeting the growth hormone receptor (GHR) for acromegaly. Data showed "robust and durable" suppression of insulin-like growth factor-1 (IGF-1) in healthy adult male volunteers, with peak reductions of 52% at the highest tested dose and more than 45% suppression out to 43 days, potentially allowing for biweekly to monthly dosing. The company plans to begin a Phase II/III study of MAR002 in mid-2026."This is compared to a maximum suppression of 48%...and greater than 45% suppression lasting to only five days with the current commercially available GHR antagonist," Marea said. MAR002 was well tolerated in healthy volunteers, with no drug-related safety signals observed. Marea also highlighted progress on its lead cardiometabolic programme, MAR001, a monoclonal antibody targeting ANGPTL4 to reduce remnant cholesterol and atherosclerotic cardiovascular disease risk. Enrolment in the Phase IIb TYDAL-TIMI 78 study is expected to finish by the end of the month, with several data readouts due in 2026. A half-life-extended version, MAR001-HLE, is advancing toward Phase III readiness with a streamlined Phase I pharmacokinetics bridging study planned for later this year.RFK Jr. adds two more members to CDC vaccine panelHealth and Human Services (HHS) Secretary Robert F. Kennedy Jr. appointed two obstetrician-gynaecologists, Kimberly Biss and Adam Urato, to the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP). Kennedy said the appointments "bring the scientific credentials, clinical experience, and integrity this committee requires" and emphasised his commitment to "transparency, gold standard science, and diverse expertise in guiding the nation’s immunization policies." The two join 11 other members selected after Kennedy fired the previous panel of experts and reconstituted ACIP last June.Urato, a maternal-foetal medicine specialist with prior academic appointments at Harvard, Tufts, and the University of South Florida, has participated in FDA advisory panels. Biss has held leadership roles at Bayfront Health/Orlando Health Bayfront Hospital and her experience includes clinical education roles and publication on COVID-19 vaccine safety for pregnant women, according to an HHS release Tuesday.In 2023, Biss told the GOP-led House subcommittee that after receiving COVID-19 vaccines, some patients in her practice had faced irregularities with their menstrual cycles that were so severe she had to perform surgeries and hysterectomies. She also testified that "my miscarriage rate from year to year went up 100% in 2021" and suggested the vaccines might have been responsible for some women entering early menopause.Meanwhile, Urato has also questioned the safety of vaccines given during pregnancy, including COVID-19, influenza, Tdap and respiratory syncytial virus. He raised concerns about the use of antidepressants in pregnancy and petitioned the FDA last year to add a boxed warning to SSRIs regarding risks of pregnancy complications and alteration of foetal brain development.

The injected copper replacement therapy restores copper homeostasis and maintains mineral levels in patients with the disorder. Less than four months after rejecting Sentynl Therapeutics and Cyprium Therapeutics’ treatment for Menkes disease, the FDA has given the partners a thumbs-up, blessing Zycubo as the first approved therapy in the U.S. for the rare neurodegenerative disorder.The quick turnaround came after Sentynl addressed a manufacturing compliance issue that had been outlined in the FDA’s complete response letter from Sept.  30. Solana Beach, California-based Sentynl resubmitted its revised application Nov. 14 and the FDA accepted it Dec. 15, establishing a Jan. 14 decision date.Accompanying the approval is a rare pediatric disease priority review voucher (PRV), which will be transferred to Cyprium. The Miami-based company developed the treatment on its own before inking (PDF) a $20 million transfer agreement with Sentynl in 2021. Two years later, the partners expanded the deal, with Sentynl taking full responsibility for development and commercialization of the program.The injected copper replacement therapy, also known as copper histidinate or CUTX-101, restores copper homeostasis and maintains mineral levels in patients with the disorder.Menkes disease is an X-linked recessive genetic condition that impairs a child’s ability to absorb and transport copper, particularly to the brain. It leads to seizures, developmental delays, intellectual disability and the failure to gain weight and grow, the companies said. It also leads to issues with the bladder, bowel, bones, muscles and the nervous and vascular systems. Children develop symptoms in infancy and typically do not live beyond 3 years. Menkes affects roughly one in every 100,000 to 250,000 live births and is more common in boys.Paving the way for the FDA nod were two single-arm clinical trials in which 66 patients were treated for up to three years. Overall survival was assessed by comparing results among treated patients to untreated patients from external control groups, according to the FDA.Median overall survival was 177.1 months for those on Zycubo compared to 17.6 months for the external control group, according to data provided by Sentynl.“The company demonstrated a large improvement in overall survival compared with untreated patients, using an innovative trial design that addressed the challenges of studying an ultra-rare disease,” Tracy Beth Hoeg, M.D., Ph.D., acting director of the Center for Drug Evaluation and Research, said in a release. Side effects reported with Zycubo include infections, respiratory problems, seizures, vomiting, fever, anemia and injection site reactions. Because copper can accumulate in the body, patients receiving Zycubo should be closely monitored for potential toxicity, the FDA said.Cyprium is a subsidiary of Florida-based Fortress Biotech, which was established in 2013 to evaluate and acquire assets that have been de-risked with strong clinical data. Fortress creates subsidiaries and forms partnerships with other companies to develop the assets.Fortress facilitated the 2024 FDA approvals of Checkpoint Therapeutics’ skin cancer therapy Unloxcyt and Journey Medical and Dr. Reddy’s rosacea treatment Emrosi. In March of last year, Sun Pharma bought out dermatology specialist Checkpoint in a deal worth up to $416 million. In addition to the PRV, Cyprium will receive milestone payments and royalties on sales of Zycubo.“We believe that our business model has demonstrated measurable success and continued execution across the portfolio,” Lindsay Rosenwald, M.D., Fortress’ CEO, said in a release. “We look forward to the potential achievement of additional upcoming milestones across our extensive pipeline of commercial and clinical-stage assets.”Sentynl also is a subsidiary, answering to India-based Zydus Lifesciences.