There were two reported cases of trials restarting and one pausing this week. Here’s a look.
There are many reasons why clinical trials may pause, although one of the more common is unexpected safety signals require investigation and potential modification of the trial protocol. Often they are restarted. There were two reported cases of trials restarting and one pausing this week. Here’s a look.
Applied Therapeutics announced the U.S. Food and Drug Administration (FDA) had lifted the hold and the AT-007 ACTION-Galactosemia Kids pediatric clinical trial will resume immediately. The trial was previously divided into two separate clinical studies, a dose escalation and biomarker study followed by a separate long-term clinical outcomes study. They have now been combined into a single two-part study. AT-007 is a CNS penetrant Aldose Reductase inhibitor to treat galactosemia.
“We thank the Galactosemia community for their patience and support, and we are grateful to the FDA for their partnership,” said Shoshana Shendelman, founder and chief executive officer of Applied Therapeutics. “We believe that the program is in a stronger position for overall success and potential approval due to our close collaboration with FDA. AT-007 represents an important advancement for Galactosemia patients, and offering a therapeutic option to children is a priority for Applied Therapeutics.”
Mustang Bio announced that the FDA had removed the clinical hold on the MB-107 pivotal Phase II trial on January 28. The agency removed the hold on the Investigational New Drug (NDA) application after reviewing a comprehensive CMC package submitted by the company in late December 2020. The company plans to initiate the pivotal Phase II trial in newly diagnosed X-linked severe combined immunodeficiency (XSCID) patients. It expects to enroll the first patient in the second quarter of 2021.
XSCID is also known as bubble boy syndrome. It is a rare genetic disorder, about 1 per 225,000 births, marked by the absence or lack of function of key immune cells, causing a severely compromised immune system and death by one year of age if untreated. They generally have no T-cells or natural killer (NK)-cells. The B-cells are normal in number, but are not functional.
The same lentiviral vector utilized in MB-107 is currently being evaluated in a Phase I/II clinical trial for XSCID in newly diagnosed infants under the age of two at St. Jude Children’s Research Hospital, UCSF Benioff Children’s Hospital in San Francisco and Seattle Children’s Hospital. It is also being tested in a Phase I/II trial at the National Institute of Allergy and Infectious Diseases (NIAID) for XSCID patients previously treated with hematopoietic stem cell transplantation and where re-treatment is indicated.
“We are pleased to have resolved the clinical hold on the MB-107 IND with the FDA, enabling us to move forward with initiating the pivotal Phase II clinical trial,” said Manuel Litchman, president and chief executive officer of Mustang. “The clinical outcomes observed in XSCID patients in the ongoing Phase I/II clinical trial continue to be encouraging.”
Immunovant voluntarily paused its ongoing Phase IIb clinical trial of IMVT-1401 in Thyroid Eye Disease (TED). Immunovant reports that they became aware of a physiological signal made up of elevated cholesterol and LDL levels in patients receiving the drug in the ASCEND GO-2 trial. In previous trial of the drug in Myasthenia Gravis (MG) and in healthy patients, cholesterol levels were not measured. “Out of an abundance of caution,” Immunovant decided to voluntarily pause dosing in both TED and in a trial in Warm Autoimmune Hemolytic Anemia in order to inform everyone involved, in addition to modifying the monitoring program.
ASCEND GO-2 is evaluating the drug in TED at different doses, each given weekly for 12 weeks. They found on preliminary, unblinded data from 40 patients through week 12, that mean LDL at week 12 had increased by about 65% in the 680-mg dose group and by about 40% in the 340-mg dose group, but not in the control group. Average HDL and triglyceride levels increased to a much lower degree. No serious cardiovascular events had been reported in IMVT-1401 clinical trials.
Oddly, Harbour BioMed, which holds the license to the drug in Greater China, conducted a preliminary review of blinded data in their clinical studies in Chinese patients with MG and Idiopathic Thrombocytopenic Purpura, and did not see similar increases in cholesterol.
