A Daiichi Sankyo and AstraZeneca drug is now available approved as first-line treatment for a type of breast cancer that is particularly difficult to treat, providing patients with a new targeted therapy that has an advantage over a Gilead Sciences product in the same class of drugs.
Friday’s regulatory decision by the FDA regarding the drug Datroway covers the treatment of triple negative breast cancer (TNBC). It gets its name from the absence of three receptors found in other types of breast cancer, meaning that therapies aimed at these targets will not work. Chemotherapy is the first line of treatment for TNBC. The immunotherapy Merck Keytruda is also approved for this setting, alongside chemotherapy. But not all TNBC patients are eligible for immunotherapy, highlighting the need for new treatment options.
Datroway is an antibody-drug conjugate (ADC) designed to target TROP2, a protein abundant on the surface of many cancer cells, including most triple-negative breast cancers. The FDA submission was based on phase 3 results showing that Datroway reduced the risk of disease progression or death by 43% compared to chemotherapy. For patients with metastatic TNBC who were not candidates for immunotherapy, Datroway led to a median progression-free survival of 10.8 months, compared to 5.6 months for the chemo arm; The median overall survival was 23.7 months for patients treated with Datroway compared to 18.7 months for those who received chemotherapy. The objective response rate was 64% for study drug versus 30% for chemotherapy. The results of the clinical trials were presented last fall at the meeting of the European Society of Medical Oncology.
The first ADC targeting TROP2 for TNBC was Gilead Sciences’ Trodelvy, approved in 2020 as a third-line or later treatment. Gilead aims to introduce this drug into earlier lines of treatment. In patients not eligible for immunotherapy, Phase 3 results presented at the same ESMO meeting, showed a 38% reduction in the risk of disease progression or death. The Gilead drug led to a median improvement of 9.7 months in progression-free survival, compared to 6.9 months for the chemo group; overall survival data were not yet mature.
For now, Datroway has the advantage over Trodelvy in TNBC. This ADC was discovered and developed by Daiichi Sankyo. In 2019, the company formed an alliance with AstraZeneca focused on Enhertu, an ADC targeting HER2. The following year, AstraZeneca paid $1 billion upfront for start a collaboration on the DS-1062which will become Datroway. Up to $5 billion more is tied to achieving regulatory and commercial milestones for Datroway, which has racked up three approvals in the past 18 months.
Datroway was first approved last year for HR-positive, HER2-negative breast cancer and then for EGFR-mutated non-small cell lung cancer. TNBC’s regulatory decision is an accelerated FDA approval based on objective response rate and duration of response. Continued approval in this indication may require additional data from a confirmatory study.
Here is a summary of other recent regulatory developments:
More cancer drug approvals
—BeOne Medicines Received FDA Approval for Beqalzi as a treatment for mantle cell lymphoma, a rare blood cancer. While Beqalzi targets the same target as AbbVie and Genentech’s blockbuster blood cancer drug Venclexta, BeOne’s drug is designed with properties intended to give it safety advantages.
—Veppanu, a drug developed by partners Arvinas and Pfizerreceived FDA approval for the treatment ER-positive, HER2-negative breast cancers with an ESR1 mutation. This is the first approval for a class of drugs that exploit a mechanism called targeted protein degradation. Veppanu will be marketed by Rigel Pharmaceuticals, which paid $85 million in advance for global rights to the small molecule.
—Daiichi Sankyo and AstraZeneca drug Enhertu expanded their FDA approval with two new indications. The first is neoadjuvant treatment (before surgery) for stage II or III HER2-positive breast cancer. The second is adjuvant treatment (after surgery) for patients with HER2-positive breast cancer who have residual invasive disease after neoadjuvant treatment.
—Bizengri, a drug from Partner Therapeutics, has expanded its label to include treatment of cholangiocarcinoma driven by NRG1 gene fusions. The partner secured U.S. rights to Bizengri from Merus, leading to the fusion protein gaining FDA approval in 2024 for the treatment of pancreatic adenocarcinoma and non-small cell lung cancer positive for NRG1 gene fusions.
—Taiho Pharmaceutical’s drug Inqovi has expanded its approval to include use alongside AbbVie and Genentech’s drug Venclexta as a treatment for adults with newly diagnosed acute myeloid leukemia. The oral small molecule Taiho was first approved by the FDA in 2020 as a treatment for myelodysplastic syndromes, including chronic myelomonocytic leukemia.
New drugs for inflammation and immunology
—AstraZeneca’s lupus drug Saphnelo is now approved in a once-weekly formulation developed for self-administration by auto-injector pen. Saphnelo was first approved for lupus in 2021. This version of the antibody drug is administered by intravenous infusion.
—Incyte received FDA Approval for Jakafi XRa sustained-release version of its oral JAK 1 and JAK 2 protein inhibitor. This drug can now be used to treat the same indications of myelofibrosis, polycythemia vera, and acute graft-versus-host disease as Jakafi, but with once-daily dosing versus twice-daily dosing of the original drug.
—Bristol Myers Squibb immunology drug Sotyktu received Approval from the European Commission as treatment for active psoriatic arthritis in adults. The drug reached patients for the first time in Europe in 2023, approved to treat moderate to severe plaque psoriasis.
—AstraZeneca Breztri Aerosphere expanded its FDA approval for maintenance treatment of asthma. Inhalable triple therapy was first approved in 2020 to treat chronic obstructive pulmonary disease.
Regulatory setbacks
-THE FDA Places Full Clinical Hold on Aardvark Therapeutics’ ARD-101which had reached phase 3 testing for the treatment of Prader-Willi syndrome, a rare metabolic disease that results in excessive overeating. Aardvark voluntarily paused the study in February after a cardiac safety signal emerged in a healthy volunteer study. The company said it will now unblind the trial data to find a path forward for the small molecule.
—After the death of a patient, the FDA suspended registrations new patients on the American sites testing evenamide, a Newron Pharmaceuticals drug under development for treatment-resistant schizophrenia. The death, which occurred at a site outside the United States, was considered by a trial investigator to be unrelated to the study drug, Newron said.
Decisions about drugs for rare diseases
—X4 Pharmaceuticals received by the European Commission approval for Xolremdi as a treatment for WHIM syndrome, an ultra-rare primary immunodeficiency. Norgine holds the European rights to the drug. FDA approved Xolremdi in 2024.
—The European Commission Palsonify approveda pill from Crinetics Pharmaceuticals developed to treat acromegaly, a rare endocrine disorder. The FDA approved Palsonify last September.
—Argenx Vyvgart medication and the injectable version Vyvgart Hytrulo expanded their approvals include the treatment of all adults with generalized myasthenia gravis (gMG), a rare neuromuscular disease. Vyvgart’s initial approval in 2021 only covered the treatment of gMG patients whose disease is caused by a particular antibody, the AChR antibody.
Other FDA approvals
—AstraZeneca obtained FDA approval for Baxfendythe first in a new class of blood pressure medications. The once-daily pill came from AstraZeneca to acquire CinCor Pharma in 2023 for $1.3 billion.
—Axsome Therapeutics’ drug Auvelity has expanded its label to include treatment of agitation associated with Alzheimer’s disease. The twice-daily pill was initially approved in 2022 for the treatment of major depressive disorder.
Public domain image by National Cancer Institute