First-in-class drug for ovarian cancer shows promise at ASCO

An experimental drug that mimics folic acid is showing early promise in treating advanced ovarian cancer.

Considering that the treatment options for patients with advanced ovarian cancer are severely limited, it’s no surprise that British researchers kicked up some buzz at the American Society of Clinical Oncology (ASCO) annual meeting on June 3, when they announced positive results from a phase 1 trial of a brand-new compound. The drug, originally owned by Amgen subsidiary Onyx Pharmaceuticals, is part of a new class of treatments that capitalize on the ability of folic acid to enter cancer cells.

Researchers from the Institute of Cancer Research (ICR) in London and the Royal Marsden NHS Foundation Trust presented data at ASCO from 15 women with advanced ovarian cancer who received the drug, called ONX-0801, as part of a larger trial. Seven of the women saw their tumors shrink significantly, according to a press release from ICR.

But the results were even better in women whose tumors expressed high levels of alpha folate receptors, which are often found in “abnormally large numbers” on ovarian cancer cells, according to ICR. The receptors latch onto folic acid and shuttle it into the tumor cells. ONX-0801 capitalizes on this mechanism by mimicking folic acid, entering the cancer cells and then inhibiting a molecule called thymidylate synthase. That causes permanent DNA damage, killing the cancer cells, according to the release.

During the trial, 7 out of 10 women whose tumors had high levels of alpha folate receptors responded well to the drug.

The researchers reported that the women in the trial did not suffer traditional side effects of chemotherapy such as hair loss and stomach upset. That’s because the treatment specifically targets cancer cells, they believe. Lead author Udai Banerji, deputy director of the drug development unit at the ICR and the Royal Marsden, suggested ONX-0801 could prove to be a “kinder treatment for ovarian cancer patients,” he said in the release.

“We have also developed tests to pick out the women who are likely to respond to the drug, making the treatment potentially more cost-effective, and ensuring other patients can receive alternative treatment,” Banerji added.

Amgen collaborated on the trial, which was funded by a specialty healthcare company called BTG, according to the release. But the future of the compound, which will be renamed BTG945, is clearly in question: The U.K.’s department of international trade chose ASCO as a venue for spotlighting the drug and making it available for licensing or partnering, according to ICR.

When Amgen laid out $10 billion for Onyx Pharmaceuticals in 2013, all eyes were on Kyprolis, the takeover target’s FDA-approved drug to treat multiple myeloma. Kyprolis is still struggling to meet the high expectations set during the buyout, however, and with competition in multiple myeloma on the rise, the company has been doubling down on its marketing efforts.

As for the continuing efforts to find new approaches to battling ovarian cancer, research presented at ASCO paints a picture of mixed success. One closely watched trial is pairing Merck’s blockbuster immuno-oncology drug Keytruda with Incyte’s IDO1 inhibitor epacadostat. The combo produced an overall response rate in ovarian cancer of just 8%, and all of those responses were partial. Another combo of Bristol-Myers Squibb’s PD-1 inhibitor Opdivo with epacadostat showed no efficacy in ovarian cancer.

Researchers at the ICR hope to move their targeted folic acid-inspired treatment into larger trials soon. “It looks a highly promising treatment with the potential to have huge benefits for women with ovarian cancer,” said ICR CEO Paul Workman in the release, “and I’m very keen to see it progress to later-stage trials.”