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FDA Updates for Week of April 29, 2024: Full Approval for Tivdak


The FDA made several approvals this week, including converting Tivdak’s accelerated approval to full approval for cervical cancer and approvals for a high-concentration formulation of Cyltezo, Xolremdi for an ultra rare immune disorder and Libervant Film for epilepsy in young children.

FDA Approves High Concentration Formulation of Cyltezo

FDA has approved Boehringer Ingelheim’s high-concentration, citrate-free formulation of Cyltezo (adalimumab-adbm), the company’s interchangeable biosimilar to Humira (adalimumab), to treat patients with multiple chronic inflammatory diseases.

The high-concentration formulation (100 mg/mL), which is now available as a pre-filled syringe or pre-filled autoinjector, is priced at a 5% discount to Humira under the brand name Cyltezo and at an 81% discount to Humira as the unbranded product Adalimumab-adbm. The low-concentration (50 mg/mL), citrate-free formulation of Cyltezo has been commercially available since July 2023.

Cyltezo’s approval for the high-concentration fomulation is based, in part, on data from clinical trial VOLTAIRE-HCLF, a phase 1 clinical trial comparing the bioavailability of high-concentration and low-concentration formulations of adalimumab-adbm.

FDA Converts Tivdak’s Accelerated Approval to Full Approval for Cervical Cancer

The FDA has approved Pfizer’s supplemental biologics license application (sBLA) granting full approval for Tivdak (tisotumab vedotin-tftv) to treat patients with recurrent or metastatic cervical cancer. Cervical cancer remains a disease with high unmet need. It was estimated that, in 2023, more than 13,960 new cases of invasive cervical cancer were diagnosed in the United States.

The FDA had granted Tivdak accelerated approval in September 2021 based on tumor response and durability of response from the innovaTV 204 pivotal phase 2 single-arm trial.

The full approval is based on efficacy and safety data from the phase 3 innovaTV 301 trial in which Tivdak demonstrated overall survival, progression-free survival and confirmed objective response rate in patients with previously treated recurrent or metastatic cervical cancer compared to chemotherapy.

In the phase 3 trial, Tivdak demonstrated a 30% reduction in the risk of death compared with chemotherapy and a 3 3% reduction in the risk of disease worsening or death compared with chemotherapy. Median overall survival for patients treated with Tivdak was 11.5 months compared with 9.5 months. for chemotherapy.

Results from the innovaTV 301 study were presented at the European Society of Medical Oncology (ESMO) Congress in October 2023. The study was conducted by Seagen.

FDA Approves Xolremdi for Ultra Rare Immune Disorder

The FDA has approved Xolremdi (mavorixafor) capsules to treat patients aged 12 and older with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome.

WHIM is an extremely rare immunodeficiency disease caused by reduced mobilization of white blood cells from the bone marrow due to oversignaling of the CXCR4/CXCL12 pathway. People with WHIM syndrome have very low blood levels of neutrophils and lymphocytes. There are about 1,000 people living with WHIM.

Symptoms can vary but patients often experience recurrent infections with a high risk of lung disease, refractory warts from underlying human papillomavirus (HPV) infection, and an increased risk of developing certain types of cancer. Current treatment involves intravenous immunoglobulin or granulocyte colony-stimulating factor (G-CSF), an immune-cell-growth molecule. These treatments, however, do not specifically target the CXCR4 genetic defect.

Developed by X4 Pharmaceuticals, Xolremdi is a selective CXC chemokine receptor 4 (CXCR4) antagonist and is the first frug approved for patients with WHIM syndrome. For patients taking the 400 mg daily dose, the wholesale acquisition priceis $496,400 annually. For patients taking the 300 mg dose, the price is $372,300 annually. PantherRx Rare has been selected as the specialty pharmacy.

X4 is offering a patient solutions through X4Connect to help patient navigate insurance coverage and financial assistance. Programs include quick start, copay assistance, bridge program, and a patient-assistance program for eligible patients.

The FDA approval was based on results of the phase 3 4WHIM phase 3 study, a 52-week study that enrolled 31 people aged 12 years and older diagnosed with WHIM syndrome. The efficacy was determined by improvement in absolute neutrophil counts, improvement in absolute lymphocyte counts, and a reduction in infections.

FDA Approves Libervant Film for Epilepsy in Young Children

The FDA has approved Aquestive Therapeutics’ Libervant (diazepam) buccal (inside of the cheek) film for children between 2 and 5 years of age who have refractory epilepsy. It is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity — including seizure clusters and acute repetitive seizures — that are distinct from a patient’s usual seizure pattern.

About 3.4 million people with epilepsy nationwide, including 470,000 children, according to the CDC. More than 90% of filled prescriptions in 2023 for this patient population were for diazepam rectal gel, Aquestive officials said.

Libervant is a benzodiazepine and is the first FDA approved orally-administered rescue product for the treatment of seizure clusters. Dosage of Libervant is based on weight and is available in 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg doses. Company officials said in an earnings call the wholesale acquisition cost is in line with the diazepam rectal gel. Diastat (diazepan) rectal gel, for example, has a list price of $379 for one kit of the 10 mg dose, according to Drugs.com.

Company officials indicated they are currently able to accept and fill non-Medicaid prescriptions. They expect to expand distribution capabilities over the coming weeks and months.

Company executives in an investor call said the company is pursuing approval for children 6 years and up. In August 2022, the FDA issued a tentative approval of Libervant to treat intermittent, stereotypic episodes of frequent seizure activity in those 12 years of age or older.

But Libervant is not expected to be available for this population until January 2027 because of existing orphan drug market exclusivity held by Valtoco (diazepam) nasal spray. Valtoco was approved by the FDA in January 2020 and its marketing exclusivity ends Jan. 10, 2027.

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