FDA Approved for Multiple Myeloma treatment: Bortezomib (formerly PS-341)

On May 13, 2003, the U.S. Food and Drug Administration (FDA) granted accelerated approval for bortezomib (formerly PS-341), Velcade.

Bortezomib (formerly PS-341), a promising new drug for the treatment of multiple myeloma, recently received accelerated approval from the U.S. Food and Drug Administration (FDA) for the therapy of patients with progressive myeloma after previous treatment. Two phase II studies of bortezomib used the same schedule of twice-weekly i.v. dosing for the first 2 weeks of each 3-week cycle. In a randomized study of 54 patients, two doses were compared (1.0 and 1.3 mg/m2) and objective responses occurred at both dose levels (23% versus 35%), including one complete response in each arm.

On May 13, 2003, the U.S. Food and Drug Administration (FDA) granted accelerated approval for bortezomib (formerly PS-341), Velcade® for Injection (Millenium Pharmaceuticals, Inc.; Cambridge, MA), for use as a single agent for the treatment of patients with multiple myeloma after two prior therapies and progressing on their most recent therapy. In 1998, Millennium Pharmaceuticals, Inc., submitted an Investigational New Drug Application for bortezomib and in January, 2003, a New Drug Application (NDA) was filed. At the time of the NDA submission, melphalan, cyclophosphamide, and carmustine had been FDA approved for myeloma treatment

• 05/13/2003: FDA Approval https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2003/21602ltr.pdf
  

• Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy Oncologist;2003 https://pubmed.ncbi.nlm.nih.gov/14657528/

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• Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies Conclusion: PS-341 was well tolerated at 1.04 mg/m(2) on this dose-intensive schedule, although patients need to be monitored for electrolyte abnormalities and late toxicities. Additional studies are indicated to determine whether incorporation of dose/body surface area yields a superior PD model to dosing without normalization. PS-341 showed activity against refractory multiple myeloma and possibly non-Hodgkin's lymphoma in this study, and merits further investigation in these populations. https://pubmed.ncbi.nlm.nih.gov/12431963/ https://ascopubs.org/doi/10.1200/JCO.2002.01.133
  

• A phase I trial of the novel proteasome inhibitor PS341 in advanced solid tumor malignancies. Clin Cancer Res; 2002 Aug https://pubmed.ncbi.nlm.nih.gov/12171876/
  

• A phase 2 study of bortezomib in relapsed, refractory myeloma N Engl J Med;2003 Conclusions: Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy. https://pubmed.ncbi.nlm.nih.gov/12826635/
  

• Bortezomib (Velcade™) in the Treatment of Multiple Myeloma https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1936263/
  

• PS-341 (VELCADE™) Versus High-Dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma Phase 3 Official Title: An International, Multi-Center, Randomized, Open-Label Study of PS-341 (VELCADE™) Versus High-Dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma This study will compare the efficacy of PS-341 versus high dose dexamethasone. NCT00048230 2002 Millennium Pharmaceuticals, Inc. https://clinicaltrials.gov/ct2/show/NCT00048230