153Sm-Lexidronam (Quadramet®)

Overview

¹⁵³Sm-Lexidronam pentasodium, also known as ¹⁵³Sm-Samarium Ethylene Diamine Tetramethylene Phosphoric Acid (EDTMP) or Quadramet^®, is a therapeutic radiopharmaceutical used primarily for palliating bone pain in patients with multiple osteoblastic skeletal metastases, which are detected using ^99mTc-bisphosphonate bone scans.

This agent was initially developed by Cytogen, leveraging technology licensed from Dow Chemical Company in 1993. Cytogen secured U.S. marketing authorization (MA) in March 1997, while European rights were transferred to CISbio, which obtained EU MA in February 1998. Between May 1999 and July 2003, production was managed by Bristol-Myers Squibb (BMS), and marketing was handled by Berlex Laboratories, a subsidiary of Schering Pharma. In 2001, Schering acquired CISbio and subsequently divested its radiopharmaceutical portfolio to IBA Molecular, which managed European sales. Meanwhile, U.S. rights reverted to Cytogen and later transitioned to Jazz Pharmaceuticals’ EUSA Pharma USA Inc.

In December 2013, Lantheus acquired the U.S. rights to Quadramet^® and currently serves as its direct manufacturer and supplier within the United States. The product’s patents expired between 2007 and 2011, allowing the emergence of generic alternatives.

Key Characteristics

• Active Ingredient: ¹⁵³Sm (Samarium)-EDTMP (Ethylene Diamine Tetramethylene Phosphoric Acid)
• Indication: Pain relief for osteoblastic metastatic bone lesions.
• Dosage: Approx. 1.0 mCi/kg.
• Formulation: Solution with ~50 mCi/mL concentration.
• Shelf-Life: 56 hours post-calibration.
• Mechanism: Bone-seeking properties of ¹⁵³Sm allow targeted radiation therapy.

Clinical Use and Combination Studies

• mCRPC (metastatic Castration-Resistant Prostate Cancer):
  • Demonstrated efficacy when combined with PSA-TRICOM (PROSTVAC), showing prolonged progression-free survival (PFS) and PSA decline.
• Advantages: High bone uptake (~2x compared to ¹⁸⁶Re-HEDP), enabling effective radiotherapy with a shorter half-life compared to alternatives like ⁸⁹Sr.

Market and Availability

• Ownership and Manufacturing:
  • US: Rights owned by Lantheus; product distributed in the US.
  • EU: Quadramet available via Curium.
• Generic Availability: Options from BRIT (SAM-2), Pars Isotope, ROTOP, and others.
• Cost: Approx. $18,500 per dose in the US (as of 2020).

Competition and Challenges

1. Historical Competitors:
   • ³²P-Sodium Phosphate.
   • ⁸⁹Sr-Strontium Chloride (Metastron).
2. Modern Competitor:
   • ²²³Ra-Radium Chloride (Xofigo): Introduced in 2013, offering therapeutic benefits alongside palliation, albeit with modest survival extension (~3 months).
3. Future Challenges:
   • Market segmentation between expensive therapeutics (e.g., Xofigo) and cost-effective options like ¹⁵³Sm generics.
   • Issues with contamination by ¹⁵⁴Eu (half-life ~8.6 years) complicating production purity.

Comments and Considerations

• Efficacy Debate: Most pain palliation agents have not shown significant overall survival (OS) benefits, except for Xofigo.
• Regulatory and Clinical Landscape: New trials and strategies might better define the positioning of ¹⁵³Sm-Lexidronam amidst the evolving oncology and radiopharmaceutical markets.
• Cost-Effectiveness: Remains pivotal, especially for countries with constrained healthcare budgets.