Several weeks after getting hit with an RTF, Y-mAbs lands approval for its other neuroblastoma candidate
Nearly two months after handing Y-mAbs a refusal to file letter for one of its main neuroblastoma candidates, the FDA gave the biotech an accelerated OK for the other — but with a box warning.
Y-mAbs, which flew mostly under the radar until a few years ago, snagged approval for naxitamab as a second-line treatment in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Patients older than 1 year old can take the drug for relapsed or refractory high-risk neuroblastoma in the bone or bone marrow. The good news cushioned last month’s blow, sending the company’s stock $YMAB — which sank more than 18% upon news of the RTF — up 10.15% as of Monday morning.
Naxitamab, now marketed as Danyelza, was granted priority review in early June. Theex-Genmab execs running Y-mAbs snagged it from Memorial Sloan Kettering, along with the biotech’s other neuroblastoma candidate, omburtamab. The approval rolled in just before Thanksgiving, a few days before the candidate’s PDUFA date.
Unlike omburtamab, which targets B7-H3, Danyelza goes after GD2 — a common antigen on the cell surface of various tumors. It’s taken thrice weekly, repeated every four weeks. According to the company’s S-1, a mouse version was used on president and founder Thomas Gad’s daughter, who was diagnosed with high-risk neuroblastoma at age 2. She later relapsed and began taking omburtamab about 11 years ago, and has been disease-free since.
“It’s very exciting to see this treatment go from being an experimental therapy used at my daughter’s bedside to now being FDA approved,” Gad said in a statement.
The FDA based its decision on two pivotal studies, which showed the drug was well-tolerated with “clinically manageable” adverse effects, according to the company. Regulators briefly put the program on a partial clinical hold back in 2017, due to “proposed acceptance criterion for the ADCC‑CD16, ADCC‑CD32, and CDC assays” which were “too wide to provide sufficient control over these attributes,” according to an SEC filing. Y-mAbs submitted a complete response to the partial hold in May 2018, and it was removed the following month.
The approval comes with a box warning, which states that Danyelza has been linked to serious infusion reactions like anaphylaxis, cardiac arrest, bronchospasm, stridor and hypotension. One case of transverse myelitis and two cases of posterior reversible encephalopathy syndrome were reported, according to the label. Severe pain and severe hypertension were also listed as potential side effects.
But the most common side effects were mostly mild and moderate, according to the label. They ranged from infusion-related reaction to peripheral neuropathy to edema.
“This approval of Y-mAbs’ first BLA represents a key step in working towards our mission of becoming a world leader in developing better and safer antibody-based oncology products addressing unmet pediatric and adult medical needs,” CEO Claus Moller said in a statement.
Going forth, the FDA is requiring a confirmatory trial with a minimum of 80 patients. The study will measure overall response rate, with duration of response as the secondary endpoint. Progression-free survival and overall survival are both long-term secondary endpoints.
As for omburtamab, Y-mAbs expects to meet with the FDA and resubmit its application by the end of the year. The RTF cited the need for more information on manufacturing and clinical modules, the company said. While it didn’t specify exactly what regulators are looking for, Y-mAbs said it will provide supplementary data from a Phase II study on tumor response from the first 24 patients in the trial.
Naxitamab is in several other Phase II trials, including pediatric front-line high-risk neuroblastoma and relapsed second-line osteosarcoma.