Refractory Neuroblastoma

Orphelia said it will continue to make Kizfizo available to paediatric patients under certain programmes and clinical trials. Credit: Andrii Yalanskyi via Getty Images. Orphelia Pharma is exploring alternative regulatory pathways for Kizfizo (temozolomide) following a negative opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP). The latest decision follows another negative opinion for Orphelia’s marketing authorisation application (MAA) in November 2024. The CHMP determined that Kizfizo failed to demonstrate sufficient clinical benefit to establish a positive benefit-risk balance. The agency cited modest response rates and the lack of convincing evidence that Kizfizo offered significant advantages over existing therapies for relapsed/refractory neuroblastoma. In response to the initial negative opinion, Orphelia requested a re-examination of the decision in December 2024. However, after a re-evaluation on 27 February 2025, the CHMP upheld its initial stance, stating that the committee’s concerns were not resolved. The company shared this update in a press release today (12 March). Orphelia emphasised that it will continue to make Kizfizo available to paediatric patients under compassionate use or early access programmes as well as to patients participating in ongoing clinical trials. “Considering the important unmet medical need, we are currently exploring all available options to make Kizfizo available to the paediatric patients,” said Laurent Martin, chief pharmaceutical affairs officer at Orphelia Pharma in the 12 March announcement. Neuroblastoma is a type of cancer that forms in certain types of nerve tissue, mostly affecting children under the age of five. Neuroblastoma is the second most common solid tumour in children after brain tumours, according to the UK-based charity The Children & Young People’s Cancer Association (CCLG). Kizfizo was designed as a hybrid medicine similar to MSD’s chemotherapy agent Temodal but is formulated as a liquid for easier administration, as many babies and children cannot take oral tablets. Orphelia presented clinical data from studies enrolling 102 patients up to 21 years old. The Phase I TEMOkids (NCT04610736) and Ped-TMZ studies (NCT04467346) demonstrated safety, pharmacokinetics, and efficacy. The ongoing Phase I/II BEACON2 study is evaluating Kizfizo in combination with chemotherapies irinotecan or topotecan. Originally indicated exclusively for the treatment of glioblastoma in adults in the US, temozolomide has been used off label to treat neuroblastoma patients for years. The drug has been approved for treating glioblastoma in adults and children in Europe since 2010. Kizfizo was granted early access authorisation by the French authorities in March 2022 and has received orphan drug designation from the EMA and the US Food and Drug Administration (FDA). The only approved drug in Orphelia’s portfolio is Kigabeq (vigabatrin), its paediatric formulation of vigabatrin, which has an EU authorisation as a monotherapy for West syndrome and for use as a combination treatment for resistant partial epilepsy.

Silmitasertib, also known as CX-4945, was originally developed by Cylene Pharmaceuticals, a San Diego-based biotech that ceased operations in 2013. Since then, Senhwa Biosciences, which is headquartered in Taiwan but also has a San Diego base gained the rights to the small molecule, first in class, casein kinase 2 (CK2) inhibitor. CK2 is overexpressed in a number of tumors. Various studies have shown silmitasertib appears to have good anticancer activity. For example ​, it triggers autophagy and promote apoptosis of cancer cells in pancreatic and lung cancer and also promotes colorectal cancer cell death. Senhwa is currently testing silmitasertib in early human trials for treatment of cholangiocarcinoma, basal cell carcinoma, medulloblastoma and neuroblastoma. In preclinical studies ​, the small molecule showed good oral bioavailability and was able to effectively inhibit tumor growth in animal studies while being well tolerated. When combined with DNA-damaging chemotherapy drugs such as gemcitabine and cisplatin, the anticancer activity of silmitasertib seems to be enhanced so it is being tested as an add-on therapy in the new trial. The phase 1/2 study will include 114 children and young adults with relapsed or refractory neuroblastoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, and liposarcoma in the US. "We are thrilled to be able to move this important research forward on a larger scale," said Giselle Sholler, division chief of pediatric hematology/oncology and director of pediatric oncology research at the College of Medicine and chairperson of the Beat Childhood Cancer Research Consortium, which is supporting the study. googletag.cmd.push(function () { googletag.display('text-ad1'); }); “The insights gained from this trial will help not only local patients and their families but can lead to new therapies that can help children throughout the US and internationally.” Additional indication for Covid-19 patients ​ As well as being a promising anti-cancer therapy, silmitasertib is being tested to treat people infected with SARS-CoV-2 who develop serious symptoms that require hospitalization in a phase 2 study. CK2 is involved in regulating signaling pathways important for innate immune responses. Inhibiting this protein kinase can help reduce the excessive cytokine storm immune response often seen in people with severe Covid-19. Studies have shown that silmitasertib and other kinase inhibitors seem to reduce levels of inflammatory biomarkers such as interleukin 6 and tumor necrosis factor-alpha, both of which are high in hospitalized Covid-19 patients. So far results phase 2 results ​ announced by Senhwa have been good with significantly better recovery times observed for Covid-19 patients given silmitasertib versus standard care, with a good safety profile.

TAIPEI and SAN DIEGO, Sept. 13, 2024 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), a new drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, today announced that its new drug Silmitasertib (CX-4945) was granted a rare pediatric disease designation (RPDD) by US FDA for the treatment of neuroblastoma. This is the recognition obtained again after Silmitasertib (CX-4945) received RPDD in medulloblastoma from the FDA in July 2020, demonstrating the great potential of Silmitasertib (CX-4945) in the development of treatments for rare pediatric cancers. Silmitasertib is a first-in-class small molecule drug that targets the CK2 protein and acts as a CK2 inhibitor that exhibited antitumor activity in pre-clinical study of neuroblastoma. The RPD designation will qualify the drug for the priority review voucher (PRV) program meant to encourage development of novel therapies for rare pediatric diseases. Silmitasetib has previously granted 1 RPD and 3 orphan drug designations (ODD) by the FDA. "The RPD designation offers sponsors the additional incentive by requesting priority review vouchers (PRVs) for their future marketing applications, and this approach encourages the drug development for the treatment of rare pediatric diseases," said Jin-Ding Huang, PhD, CEO of Senhwa Biosciences, Inc. Neuroblastoma, an embryonic tumor of the peripheral sympathetic nervous system, is the third most common pediatric cancer and the most common cancer in infants. It is mostly diagnosed in infancy at an average of 1 to 2 years old. There are an estimated 700 to 800 new cases of neuroblastoma each year in the United States. While low and intermediate-risk neuroblastoma have a very high rate of survival, high-risk neuroblastoma has a 5-year survival rate of about 50%, and it has a high likelihood of recurrence even with intense multimodal treatments. There is currently no standard treatment for patients with relapsed/refractory neuroblastoma. SOURCE Senhwa Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED