AstraZeneca Wins First FDA Drug Nod for NF1, a Rare Genetic Disorder

Xconomy National — 

An AstraZeneca drug designed to block tumor growth is now approved as a treatment for neurofibromatosis type 1 (NF1), a rare inherited disorder that leads to tumors on nerves throughout the body.

The FDA’s Friday decision for the drug, selumetinib (Koselugo), makes it the first approved treatment for NF1. It’s also the latest twist in a winding path. The small molecule has been developed under the watch of several companies besides AstraZeneca (NYSE: AZN), and it has been tested in a number of cancers—unsuccessfully in some cases.

NF1 is a nervous system disorder that is typically diagnosed early in childhood. The tumor growths on nerves are caused by a genetic mutation. These tumors are typically benign but they can lead to discolored spots on the skin, seizures, speech difficulty, and skeletal problems that include progressive spinal curvature and bowing of the legs, according to the National Organization for Rare Disorders. The disease occurs an estimated once in every 2,500 to 3,000 births. Treatment includes surgery to remove the tumors.

Approval of selumetinib covers patients whose tumors can’t be removed or are too risky to remove. The drug is a kinase inhibitor—it blocks MEK, an enzyme that is key in signaling pathways for cancer cell growth. The FDA says its decision is based on a clinical trial conducted by the National Cancer Institute. Results from 50 patients given the AstraZeneca drug showed that 66 percent exhibited a 20 percent or greater reduction in tumors, as assessed by an MRI scan. All patients had a partial response to the drug, which means that no one experienced a complete disappearance of tumors. But 82 percent of the patients had a response to the drug that lasted a year or more.

The FDA says common side effects observed in clinical tests included vomiting, rash, abdominal pain, diarrhea, nausea, joint pain, and itching. The regulator also cautions that the drug may lead to more serious complications such as heart failure and vision problems. The FDA says patients should have heart and eye assessments before starting on selumetinib and during treatment. Other potential problems include muscle damage and bleeding.

Selumetinib was initially developed by Array Biopharma, a Boulder, CO, cancer drug developer that had tested it in a range of solid tumors, including lung cancer, melanoma, and thyroid cancer. The drug was one of three cancer compounds included in a development partnership with AstraZeneca that dates to 2003. AstraZeneca eventually took on later-stage development of selumetinib. In 2016, the company announced that the drug failed a Phase 3 test in non-small cell lung cancer. The pharmaceutical giant continued clinical development of the compound in thyroid cancer and NF1.

In 2017, AstraZeneca signed on Merck (NYSE: MRK) as a collaborator. That deal focused on olaparib (Lynparza), an AstraZeneca cancer drug that won its first FDA approval in 2014. The alliance also included selumetinib, which the partners would continue developing. Last November, the FDA accepted AstraZeneca’s application for review of the drug as a treatment for NF1.

Now that selumetinib is approved, milestone payments and royalties from its sales are expected to go to Pfizer (NYSE: PFE). Array was due those payments under its agreement with AstraZeneca. Last year, Pfizer acquired Array for $11.4 billion, a deal that puts the pharmaceutical giant in line for the payments owed to its new subsidiary.

Selumetinib’s approval grants AstraZeneca a rare pediatric disease priority review voucher, which is like a ticket granting its owner speedier review of another drug. The FDA created this program as a way of incentivizing development of more rare disease drugs. But these vouchers can be bought and sold, making them commodities in their own right. In some cases, companies pay hundreds of millions of dollars to acquire a voucher.

Image: iStock/Olivier Le Moal