November 30, 2020 -- Welcome to this week's edition of Regulatory Roundup. This past week, several novel therapies for the treatment of rare diseases and cancers have received approvals, including monoclonal antibodies, immunotherapy drugs, and a lentiviral gene therapy. Roche also received expanded use approval for its flu treatment.
AB201, Arca Biopharma
The U.S. Food and Drug Administration (FDA) has granted a fast track drug development designation to the investigation of AB201 as a potential treatment for COVID-19. Arca Biopharma intends to initiate a phase IIB clinical trial (Aspen-COVID-19) of AB201 in approximately 100 patients hospitalized with COVID-19 in December 2020, with topline trial data anticipated in the second quarter of 2021.
AB201 is a small recombinant protein being developed as a potential treatment for RNA virus-associated diseases. AB201 is a potent, selective inhibitor of tissue factor, which has been identified as playing a central role in the inflammatory response to viral infections and in the process of viral dissemination. AB201 has previously undergone phase I and phase II testing in more than 700 patients.
Baloxavir marboxil, Roche
The FDA has approved Roche's supplemental new drug application for baloxavir marboxil (Xofluza) as a treatment to prevent influenza in individuals over 12 years of age following contact with someone with influenza (post-exposure prophylaxis). The approval is based on results from the phase III Blockstone study, which showed that only 1% of participants treated with the drug developed influenza compared to 13% of the placebo-treated group.
Xofluza is an antiviral designed to inhibit the cap-dependent endonuclease protein, which is essential for viral replication. It is already FDA-approved to treat acute uncomplicated influenza in people 12 years of age and older who have had influenza symptoms for no more than 48 hours.
Nivolumab, Bristol Myers Squibb (BMS)
The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with advanced, recurrent, or metastatic esophageal squamous cell carcinoma after chemotherapy. The approval is based on results from the phase III Attraction-3 trial, which demonstrated a statistically significant and clinically meaningful improvement in overall survival in patients who received Opdivo versus chemotherapy.
Opdivo is a programmed cell death 1 (PD-1) immune checkpoint inhibitor designed to harness the body's own immune system to help restore anti-tumor immune responses. The immunotherapy is currently approved for other indications in more than 65 countries, including the U.S., the European Union, Japan, and China.
MB-107/MB-207, Mustang Bio
The EC has issued a positive opinion on Mustang Bio's application for orphan drug designation for its lentiviral gene therapy treatments (MB-107 and MB-207) for the treatment of X-linked severe combined immunodeficiency (XSCID).
First, to MB-107 for the treatment of newly diagnosed infants between two months and two years of age. The treatment is currently being assessed in a phase I/II clinical trial at St. Jude Children's Research Hospital, the University of California, San Francisco Benioff Children's Hospital, and the Seattle Children's Hospital. Mustang has submitted an investigational new drug application (IND) to the FDA to initiate a multicenter phase II trial of MB-107 in this same patient population.
Second, to MB-207 for the treatment of patients who have been previously treated with hematopoietic stem cell transplantation who need retreatment. MB-207 is currently being assessed in a phase I/II clinical trial at the National Institute of Allergy and Infectious Diseases. Mustang expects to file an IND with the FDA to initiate a multicenter phase II trial of MB-207 in the first quarter of 2021.
The European Medicines Agency (EMA) has previous granted MB-107 advanced therapy medicinal product classification in April 2020. The FDA has previously granted both MB-107 and MB-207 rare pediatric disease and orphan drug designations, as well as regenerative medicine advanced therapy designation to MB-107.
Guselkumab, Johnson & Johnson
The EC has approved guselkumab (Tremfya) for the treatment of patients with active psoriatic arthritis who have not responded to prior disease-modifying antirheumatic drug therapy. Tremfya is the first approved fully human monoclonal antibody that selectively binds to the p19 subunit of interleukin 23 (IL-23) and inhibits its interaction with the IL-23 receptor. It is already approved for the treatment of patients with moderate to severe plaque psoriasis.
The new indication approval is based on results from the Discover-1 and Discover-2 phase III clinical studies. The clinical studies showed that patients with active psoriatic arthritis achieved statistical significance in the primary end point of the American College of Rheumatology 20% improvement (ACR20) response compared to the placebo.
The marketing authorization follows a positive opinion from the Committee for Medicinal Products for Human Use of the EMA issued on October 15.
CX-5461, Senhwa Biosciences
Senhwa Biosciences has submitted multiple IND applications to the FDA and Health Canada evaluating its investigational drug, CX-5461, for the treatment of patients with solid tumors with BRCA2 or PALB2 mutations. The drug will be used in combination with Pfizer's poly (ADP-ribose) polymerase inhibitor, Talazoparib, to explore the therapeutic potential in prostate cancer. CX-5461 is designed to stabilize DNA G-quadruplexes of cancer cells and leads to disruption of the cell's replication fork.
Naxitamab-gqgk, Y-mAbs Therapeutics
The FDA has approved naxitamab-gqgk (Danyelza) in combination with granulocyte-macrophage colony-stimulating factor for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma. Danyelza is a humanized, monoclonal antibody that targets the ganglioside GD2, which is highly expressed in various neuroectoderm-derived tumors and sarcomas. The drug is administered to patients three times a week in an outpatient setting and the treatment is repeated every four weeks.
The approval is supported by clinical evidence from two studies in patients with high-risk neuroblastoma with refractory or relapsed disease. The drug appears to be well-tolerated and adverse events were clinically manageable. Danyelza has previously received priority review, orphan drug, breakthrough therapy, and rare pediatric disease designations from the FDA.