A new day for pediatric cancer patients: Day One's share price doubles on initial data for brain tumor drug

Day One Biopharmaceuticals appears to be living up to its namesake of altering pediatric cancer care from day one, unveiling positive initial data for its brain tumor drug that saw its share price double on Monday morning.

Though the positive news for the tovorafenib therapy comes from a small dataset—22 patients in the ongoing phase 2 Firefly-1 clinical trial—the overall response rate of 64% was enough to send the biotech’s shares skyrocketing 109% to $13.82. 

The trial studied tovorafenib as a monotherapy for relapsed/progressive pediatric low-grade glioma (pLGG), the most common brain tumor diagnosed in children. With no approved therapies for pLGG, current treatment approaches have been tied to significant acute and life-long adverse effects, the company said.

As well as the overall response rate, the initial data from the trial's first 22 patients found a clinical benefit rate—defined as a partial response or unconfirmed partial response plus stable disease—in 91% of participants. The median time-to-response was 2.8 months, the company said.

Fourteen patients had partial responses to treatment, while disease remained stable in six patients, with tumor shrinkage reported in all six of these individuals.

The data was taken from a heavily pretreated population, with a median of three prior lines of therapy recorded. No patients discontinued treatment due to treatment-related adverse events (AEs), and the most common grade 1 or 2 AEs were an increase in blood creatine phosphokinase, rash, and hair color changes. Treatment-related AEs of grade 3 or higher occurred in nine patients.

Day One plans to expand tovorafenib to be a front-line therapy for patients newly diagnosed with pLGG harboring a BRAF alteration, with the first patient expected to be dosed in a phase 3 trial for this indication in the third quarter of the year. The trial, dubbed Firefly2, will be a collaborative work with the Low-Grade Glioma in Children (LOGGIC) consortium and a network of pediatric oncology centers.     

The trial will evaluate once-weekly monotherapy tovorafenib, aiming to enroll approximately 400 patients aged 6 months to 25 years across 100 sites around the world.

Full topline results from the ongoing Firefly-1 trial are expected in the first quarter of next year, and if the data are positive, Day One hopes to submit an application for approval to the FDA in the first half of 2023.

Day One is also evaluating tovorafenib alone or as a combination therapy for adolescent and adult patients with recurrent or progressive solid tumors with MAPK pathway aberrations in its phase 2 Firelight-1 trial.

The biotech licensed tovorafenib—a highly-selective type 2 pan-RAF kinase inhibitor—from Sunesis Pharma. It has already been granted breakthrough therapy and rare pediatric disease designations by the FDA for patients with pLGG harboring an activating BRAF alteration, as well as orphan drug designation from the FDA for treating malignant glioma.

Founded to tackle the lack of treatment options in pediatric cancer, Day One’s name reflects its mission to redefine “the day one talk” clinicians have with patients and families about initial diagnosis and treatment plan. Despite scores of new cancer medicines approved in recent years—such as checkpoint inhibitors, new targeted treatments and CAR-T therapies—children often remain an afterthought in cancer drug development.