Swiss drugmaker Novartis made a big investment in radiopharmaceuticals with the Thursday announcement that it will acquire a US firm with an oncology drug in late-stage development.
The company said it would acquire Endocyte, headquartered in West Lafayette, Indiana, for $2.1 billion, or $24 per share. The company has a radioligand therapy, Lu-PSMA-617, in Phase III development for metastatic castration-resistant prostate cancer. Endocyte’s stock opened 50 percent above Wednesday’s closing price on the news.
The radioligand therapy, or RLT, uses a ligand, or small molecule that is designed to bind to a protein expressed on the surfaces of most prostate cancer cells – but not normal cells – called prostate-specific membrane antigen, according to Endocyte’s website. The ligand in the drug is chemically attached to a radioactive atom, lutetium-177, which then releases a particle to deliver radiation directly to the cell and kill it. The Phase III study, VISION, enrolled its first patient in June. It is set to enroll 750 patients and has an estimated primary completion date of August 2020, according to its entry on the ClinicalTrials.gov database.
Data from a Phase II study of the drug presented in a poster in June at the American Society of Clinical Oncology’s annual meeting indicated that of the 50 patients receiving Lu-PSMA-617, 62 percent had a greater than 50 percent reduction in their prostate-specific antigen levels, while 44 percent of patients had a PSA reduction of 80 percent or more. Median overall survival in the first 30 patients enrolled in the Phase II study was 13.5 months, and median PSA progression-free survival – a measure of how long patients live without their disease worsening – was 7.6 months.
PSA reduction is a surrogate marker, meaning it is potentially indicative of improvement in overall survival, a harder endpoint that indicates how long patients live and the primary endpoint that VISION is designed to investigate. In oncology, a Phase II study showing an improvement based on a surrogate marker is usually considered sufficient cause to test a drug in a Phase III study.
Endocyte is also developing a preclinical adaptor-controlled CAR-T therapy, which is designed to overcome traditional CAR-Ts’ reliance on the activity and specificity of T cells engineered to recognize specific, naturally expressed targets. Novartis markets the first Food and Drug Administration-approved CAR-T, Kymriah (tisagenlecleucel), which is engineered to target CD19, an antigen expressed on the cells of acute lymphoblastic leukemia and diffuse large B-cell lymphoma, for which it is approved.
Another company developing drugs that deliver targeted radiotherapies is New York-based Actinium Pharmaceuticals. Actinium is developing a suite of radioimmunotherapies, which consist of radioisotopes conjugated via biochemical linkers to monoclonal antibodies, mainly for blood cancers. Its therapies are similar to antibody-drug conjugates, which consist of a cytotoxic drug conjugated using linkers to monoclonal antibodies, such as Pfizer’s Mylotarg (gemtuzumab ozogamicin) for acute myeloid leukemia and Seattle Genetics’ Adcetris (brentuximab vedotin) for Hodgkin’s lymphoma and T-cell non-Hodgkin’s lymphoma.
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