AstraZeneca's selumetinib moves past cancer failures to nab FDA priority review in neurofibromatosis

FDA Building 2
After years of disappointments from its MEK inhibitor selumetinib, AstraZeneca got a welcome reprieve from the FDA. (FDA)

Ever since AstraZeneca licensed the experimental MEK 1/2 inhibitor selumetinib from Array BioPharma in 2003, the drug has been nothing but trouble, failing multiple cancer trials and landing at the center of a royalty dispute.

Now the British drugmaker finally has some good news about it.

On Thursday, the FDA granted priority review to selumetinib to treat children with the rare neurological disorder neurofibromatosis type 1. The FDA should make a ruling on the drug in the second quarter of 2020, according to an announcement from AZ, which is co-developing the product with Merck & Co.

The approval would cover NF1 patients who've developed plexiform neurofibromas, a type of tumor associated with the disease, that cannot be treated with surgery. The condition is inherited and it is rare, affecting about one in every 3,000 or 4,000 people.

AZ and Merck submitted selumetinib for FDA approval based on a phase 2 trial in which 66% of patients had a complete or partial response to the therapy, which is a twice-daily pill. The FDA has also given the drug its coveted “breakthrough therapy” and orphan designations, solidifying a speedy review and the potential for seven years of market exclusivity in NF1.

That would be a welcome reprieve from all the hassles AZ has faced with selumetinib. The drug proved ineffective in a phase 3 trial in KRAS mutation-positive non-small cell lung cancer (NSCLC), and also in metastatic uveal melanoma when combined with the chemotherapy medicine dacarbazine.

AstraZeneca had obtained orphan designation for selumetinib in thyroid cancer, but that pursuit fell short, too. Last July, AZ announced that the trial of the drug in thyroid cancer did not meet its primary endpoint and that the phase 3 in that indication would be axed.

RELATED: AstraZeneca’s selumetinib flops in thyroid cancer, adding to list of failures

AZ hasn’t completely given up on selumetinib in cancer, however. Its pipeline lists two ongoing oncology trials involving the drug: a phase 1 study of selumetinib combined with Imfinzi, AZ’s PD-L1 inhibitor, in solid tumors, and a phase 2 combining either it or a MET inhibitor with the company’s Tagrisso in EGFR-mutated NSCLC.

It isn’t clear exactly why selumetinib has been a disappointment in cancer, but one academic team recently teamed up with AstraZeneca to try to figure that out. In May, researchers at the U.K.-based Babraham Institute released a study showing how cancer cells are able to avoid destruction with selumetinib. Interestingly, they also discovered that the same strategy causes cancer cells to die—but not until the drug therapy is stopped.

RELATED: AstraZeneca owes $192M in royalties from massive Merck deal, selumetinib licensor Array argues

Amid all the work to try to make selumetinib a success, a legal battle broke out between Array, AZ and Merck. Last year, Array sued AZ for breach of contract, alleging that the British drug giant owes $192 million in royalties on selumetinib stemming from the Merck partnership, which could be worth up to $8.5 billion.

Rare diseases can be lucrative for drug companies, so it’s no surprise AZ and Merck have some competition brewing in NF1-PN. In September, SpringWorks Therapeutics pulled off a $162 million initial public offering with plans to advance its MEK inhibitor mirdametinib through late-stage clinical trials in NF1-PN. The company, a Pfizer spinoff, had previously raised $228 million in venture capital.

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