FDA Update for Week of July 25

The FDA has approved lupus therapy for children and allows importation of contrast medium. The agency has accepted applications for several therapies, including for a Tysabri biosimilar, a therapy for a genetic form of ALS, and an immunotherapy for bladder cancer, as well as for Enhertu in low HER2 breast cancer. Additionally, AbbVie seeks additional indication for Rinvoq.

FDA approves Benlysta for children 5 years and up.

The FDA has approved GSK’s Benlysta (belimumab) to treat children aged 5 to 17 with active lupus nephritis (LN), a serious inflammation of the kidneys caused by lupus that can lead to end-stage kidney disease. It was previously approved for adults with systemic lupus erythematosus.

This is the first FDA-approved treatment for pediatric LN, which remains a driving factor in increased complications, hospitalizations and mortality rates in children. Prior to this, treatment options for children were mainly limited to use of non-selective immunosuppressants and corticosteroids.

Benlysta is a human monoclonal antibody that binds to soluble BLyS and inhibits the survival of B cells. First approved in 2011, it is the first and only approved biologic for both systemic lupus erythematosus and lupus nephritis in more than 50 years.

FDA gives okay for Bracco to import contrast medium.

The FDA has allowed Bracco Diagnostics to import Iomeron (iomeprol injection) into the United States to address the ongoing iodinated contrast media shortage. Iodinated contrast media are contrast agents that contain iodine atoms used for x-ray-based imaging such as computed tomography (CT).

Iomeron is an iodinated contrast medium for intravascular use in adults in various imaging procedures. It is currently registered in more than 50 countries in Europe and Asia, but it is not approved for use in the United States. Iomeron will be temporarily available in the United States at the end of August 2022. It is manufactured at two Bracco locations: BIPSO in Germany and Patheon in Italy.

The FDA is allowing this importation to address shortages of GE Healthcare’s Omnipaque (iohexol injection) and Visipaque (iodixanol injection), as well as Bayer’s Ultravist (iopromide injection).

GE Healthcare, in particular, has experienced challenges related to manufacturing Omnipaque and Visipaque because of the COVID-19 pandemic. The company’s plant is located in Shanghai, which has experienced closures related to China’s COVID-19 policies. This has created supply disruption. In a statement issued July 15, 2022, the company said the Shanghai facility is operating at full capacity but indicated that there will continue to be reduced availability of its iodinated contrast media.

The supply of Bayer’s Ultravist has also experienced disruption because of the pandemic. In June 2022, the company announced it had received approval from the FDA to import Ultravist with non-U.S. labeling. The product to be imported is manufactured at the same site in Germany as the U.S.-label Ultravist, but doesn’t include FDA approved labeling and the package inserts may differ. The bar codes are also different, the company indicated

FDA accepts BLA for Tysabri biosimilar.

The FDA has accepted Sandoz’ biologics license application (BLA) for a first-of-a-kind biosimilar natalizumab, which references Biogen’s Tysabri. Sandoz, a subsidiary of Novartis, is seeking approval to treat patients with the relapsing forms of multiple sclerosis (MS), relapsing-remitting MS, active secondary progressive disease in adults, and Crohn´s Disease.

Sandoz’ biosimilar natalizumab, developed by Polpharma Biologics, has the same intravenous dosage form, route of administration, dosing regimen and presentation as Tysabri. Sandoz officials expect the review of the application to take about 12 months.

The European Medicines Agency (EMA) also accepted the marketing authorization application (MAA) for this proposed biosimilar natalizumab, covering treatment as a single disease-modifying therapy (DMT) in adults with highly active relapsing-remitting MS, the same indication as approved by the EMA for reference medicine Tysabri.

Both the FDA and EMA applications include data from the phase 1 and phase 3 Antelope studies in patients with relapsing-remitting MS. The studies met their primary endpoints, showing that the biosimilar matches the reference medicine in terms of efficacy, safety and immunogenicity.

FDA accepts NDA for therapy for genetic form of ALS.

The FDA has accepted a new drug Application (NDA) for tofersen to treat patients with superoxide dismutase 1 amyotrophic lateral sclerosis (SOD1-ALS), a rare, genetic form of the disease. The agency has granted the application priority review and given a Prescription Drug User Fee Act action date of Jan. 25, 2023. The FDA indicated that it is planning to hold an advisory committee meeting for this application. If approved, tofersen will be the first treatment that targets a genetic cause of ALS.

Developed by Ionis Pharmaceuticals and licensed to Biogen, toferson is an antisense drug that binds to SODI mRNA, which leads to its degradation.

Biogen is seeking approval under the accelerated approval pathway and based on the use of a neurofilament as a surrogate biomarker. Neurofilaments are normal proteins found in healthy neurons; they are increased in blood and cerebrospinal fluid when damage has been done to neurons or their axons and are a marker of neurodegeneration. In ALS, higher levels of neurofilaments have been found to predict more rapid decline in clinical function and shortened survival.

FDA accepts BLA for immunotherapy for bladder cancer.

The FDA has accepted the biologics license application (BLA) for ImmunityBio’s N-803, an IL-15 superagonist in combination with Bacillus Calmette-Guérin (BCG) vaccine. The company is seeking approval for N-803, an antibody cytokine fusion protein with the brand name of Anktiva, to treat patients with BCG-unresponsive non-muscle-invasive bladder cancer carcinoma in situ. The BCG vaccine is the current standard of care in this cancer.

The Prescription Drug User Fee Act target action date is May 23, 2023. The FDA has granted N-803 — with the brand name Anktiva — breakthrough therapy and fast track designations.

If approved, N-803 plus BCG would be the first immunotherapy combination for this indication in 23 years that can be delivered directly to the bladder to induce natural killer cells and T cells. N-803 has a unique mechanism of action that leads to the proliferation of NK and T cells that are cells of the adaptive and innate immune system. Through this action, N-803 provides a secondary boost to the immunological response generated by BCG for bladder cancer, or by a checkpoint inhibitor for other indications.

FDA accepts sBLA for Enhertu in low HER2 breast cancer.

The FDA has accepted the supplemental biologics license application (sBLA) of Enhertu (famtrastuzumab deruxtecan-nxki) to treat adult patients with metastatic breast cancer with low HER2 expression. The application has been granted priority review, and the Prescription Drug User Fee Act date (PDUFA) action date is during the fourth quarter of the 2022.

The sBLA is being reviewed under the Real-Time Oncology Review (RTOR) program and Project Orbis, two initiatives of the FDA designed to bring cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application. Project Orbis provides a framework for concurrent submission and review of oncology medicines among participating international partners.

Enhertu is an engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.

AbbVie submits supplemental applications for Rinvoq.

AbbVie has submitted applications for a new indication to the FDA and European Medicines Agency (EMA) for Rinvoq (upadacitinib) to treat adult patients with moderate-to-severe active Crohn’s disease.

The applications are supported by data from three phase 3 clinical trials, including two induction studies (U-EXCEED and U-EXCEL) and one maintenance study (U-ENDURE). Across all three studies, significantly more patients treated with Rinvoq achieved the co-primary endpoints of clinical remission and endoscopic response.