Top 5 Rare Disease News of the Week—August 12, 2018

#5: Gene Responsible for Recessive Spondylocarpotarsal Synostosis Syndrome Identified

Investigators from the University of Otago in New Zealand have identified that mutations in both the FLNB gene and the MYH3 gene are the cause of a rare genetic disease that results in the fusion of bones in the spine and limbs: spondylocarpotarsal synostosis syndrome (SCTS).

This is the first time that more than one gene has been implicated as the cause of this disorder, illustrating the valuable insight that genomic analysis can provide.

Stephen Robertson, BMedSc, MB, ChB, FRACP, DPhil, Cure Kids Professor of Paediatric Genetics at University of Otago, a global expert in single gene disorders that occur in children, explained his team at the Clinical Genetics Group’s inspiration for the study in an exclusive interview with Rare Disease Report^®.

#4: Acebilustat Reduces Frequency of Pulmonary Exacerbations in Cystic Fibrosis Patients

Read more about the mutations in both the FLNB gene and the MYH3 gene found to be responsible for recessive spondylocarpotarsal synostosis syndrome (SCTS).

Data from Celtaxsys, Inc.’s phase 2 EMPIRE-CF trial evaluating acebilustat (CTX-4430) for the treatment of cystic fibrosis, irrespective of the causative genotype, have been released.

The first novel, oral, once-daily anti-inflammatory molecule showed evidence of clinically meaningful improvements in pulmonary exacerbations (PEx) by both reducing the frequency of the exacerbations and increasing time to next exacerbation over 48 weeks of therapy. The findings have inspired plans for a phase 3 trial.

"The emerging standard for efficacy in the evaluation of anti-inflammatory therapy in cystic fibrosis is a reduction in pulmonary exacerbations, which are associated with disease progression,” US principal investigator for the EMPIRE-CF trial, Steven Rowe, MD, MSPH, professor of medicine and the director of the Gregory Fleming James Cystic Fibrosis Research Center at the University of Alabama at Birmingham, told Rare Disease Report^®. “While caution is needed since this was a secondary outcome measure that did not reach statistical significance, the consistent benefit observed among cystic fibrosis patients treated with acebilustat, across several pre-defined subgroups, is a compelling finding.”

#3: First Patients with Primary or Enteric Hyperoxaluria & Advanced Chronic Kidney Disease Treated with ALLN-177

Read more about acebilustat’s ability to reduce the frequency of pulmonary exacerbations in patients with cystic fibrosis.The first patients have been treated in a phase 2 trial evaluating Allena Pharmaceuticals, Inc.’s ALLN-177 in adults and adolescents with primary hyperoxaluria or enteric hyperoxaluria with advanced chronic kidney disease (CKD) and elevated plasma oxalate.

A first-in-class, non-absorbed, orally-administered enzyme, ALLN-177 is optimized to degrade oxalate within the gastrointestinal (GI) tract to treat severe hyperoxaluria, a metabolic disorder characterized by elevated urinary oxalate levels.

In an exclusive interview with Rare Disease Report^®, Felix Knauf, MD, a nephrologist from Charité at University Medicine Berlin who advised Allena on the study design for the trial, (Study 206), and who will be 1 of the European investigators, described the significance of the drug’s potential for patients with primary hyperoxaluria or enteric hyperoxaluria with advanced CKD.

“Usually, the affected patients have chronic disease that lasts over many years and gets worse over time with regards to the complications and the severity of the disease. Therefore, the new drug has the hopes of particularly helping these chronically affected patients to find a treatment that will prevent the complications [of the disease],” he said.

#4: Relatives of Patients with Myeloid Blood Cancer at Two-Fold Risk of Disease

Read more about the first patients with primary or enteric hyperoxaluria and advanced chronic kidney disease treated with ALLN-177.A team of scientists at The Institute of Cancer Research (ICR), in London, England, and the German Cancer Research Centre in Heidelberg, Germany, have found that relatives of individuals with certain types of blood cancer may harbor inherited genetic changes that could influence their risk of developing diseases that arise from myeloid cells.

The investigators postulate that their findings could assist in identifying individuals at greatest risk of these diseases and where genetic testing, medical observation, and counseling could be beneficial in the future. The data may also lead to new research that could decipher the genetic causes of myeloid blood cancers.

"Our study provides the strongest evidence yet for inherited risk for these diseases—evidence that has proved evasive before in part because these cancers are relatively uncommon, and our ability to characterize these diseases has, until recently, been limited,” said lead author, Amit Sud, MBChB (Hons), MRCP, PhD, clinical research fellow at the Institute of Cancer Research, in a recent statement.

#5: Ewing's Sarcoma Treatment, CLR 131, Granted Rare Pediatric Disease Designation

Read more about how relatives of patient with myeloid blood cancers are at a two-fold risk of developing disease.Cellectar Biosciences’ CLR 131 was granted a rare pediatric disease designation by the US Food and Drug Administration (FDA) this morning, August 13, 2018, for the treatment of Ewing’s sarcoma, a rare pediatric bone cancer.

“We are delighted to announce receipt of our third RPDD from the FDA, which underscores Cellectar’s commitment to rare pediatric cancers. There is a critical need to develop new therapies to fight deadly childhood cancers such as Ewing’s sarcoma, and CLR 131 has shown early promise in this arena,” said John Friend, MD, chief medical officer of Cellectar Biosciences, in a recent statement.

Plans for a phase 1 trial are currently underway to evaluate CLR 131 for the treatment of Ewing’s sarcoma, rhabdomyosarcoma, osteosarcoma, neuroblastoma, high-grade glioma, and lymphomas. An accelerated phase 1 trial designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of CLR 131 in pediatric patients with these cancer types has been granted clearance by the FDA.

Read more about the FDA’s rare pediatric designation to CLR 131 for the treatment of Ewing’s sarcoma.