Following a priority review, partners Astrazeneca plc and Merck & Co. Inc. have gained a green light from the FDA for U.S. marketing of the oral MEK 1/2 inhibitor Koselugo (selumetinib) for the treatment of NF1, a rare, progressive condition caused by a genetic mutation that appears in an estimated one out of every 3,000 infants.

According to a Cortellis forecast, the medicine could generate revenues of $20 million this year and $65 million in 2021. Sales could reach $224 million by 2024, analysts predict. Like development costs of the medicine since the original co-development agreement in July 2017, Astrazeneca and Merck will equally split profits from sales.

Astrazeneca originally licensed selumetinib from Array Biopharma Inc. in a 2003 deal valued at $95 million at the time. Since then, Astrazeneca and Merck have continued to develop selumetinib, which has also been evaluated for its potential to treat acute lymphoblastic leukemia, neurofibromatosis type II and metastatic non-small-cell lung cancer. Earlier attempts to develop the drug for advanced thyroid cancer were discontinued.

Koselugo was approved specifically for patients, 2 and older, who have symptomatic, inoperable plexiform neurofibromas (PN), or tumors involving the nerve sheaths. Between 30% and 50% of patients born with NF1 develop one or more PNs. The drug, formerly known as MK-5618, functions by blocking the mitogen-activated protein kinase enzymes MEK1 and MEK2, thus helping to stop the tumor cells from growing.

"Everyone's daily lives have been disrupted during the COVID-19 pandemic, and in this critical time we want patients to know that the FDA remains committed to making patients with rare tumors and life threatening diseases, and their unique needs, a top priority," said Richard Pazdur, the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research.

The approval was based on positive results seen in 50 patients who participated in the National Cancer Institute Cancer Therapy Evaluation Program-sponsored SPRINT phase II Stratum I trial. The study measured the overall response rate (ORR) – defined as the percentage of patients with a complete response and those who experienced more than a 20% reduction in PN volume on MRI that was confirmed on a subsequent MRI within three to six months. The ORR was 66% and all patients had a partial response, meaning that no patients had complete disappearance of the tumor, the FDA said. Of those patients, 82% had a response lasting 12 months or longer.

Common side effects for patients taking Koselugo were vomiting, rash, abdominal pain, diarrhea, nausea, dry skin, fatigue, musculoskeletal pain, fever, acne, stomatitis, headache, paronychia and pruritus. It can also cause serious side effects, including heart failure, ocular toxicity and increased creatinine phosphokinase levels. It may cause harm to a newborn baby when administered to a pregnant woman, too, the FDA said.

Neither Astrazeneca nor Merck had released information about initial availability or pricing of the drug in the time shortly following the approval.

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