Bexarotene ligand pharmaceuticals

Curr Opin Investig Drugs. 2000 Dec;1(4):514-23.


Bexarotene (LGD-1069), from Ligand, was the first retinoid X receptor (RXR)-selective, antitumor retinoid to enter clinical trials. The company launched the drug for the treatment of cutaneous T-cell lymphoma (CTCL), as Targretin capsules, in the US in January 2000 [359023]. The company filed an NDA for Targretin capsules in June 1999, and for topical gel in December 1999 [329011], [349982] specifically for once-daily oral administration for the treatment of patients with early-stage CTCL who have not tolerated other therapies, patients with refractory or persistent early stage CTCL and patients with refractory advanced stage CTCL. The FDA approved Targretin capsules at the end of December 1999 for once-daily oral treatment of all stages of CTCL in patients refractory to at least one prior systemic therapy, at an initial dose of 300 mg/m2/day. After an NDA was submitted in December 1999 for Targretin gel, the drug received Priority Review status for use as a treatment of cutaneous lesions in patients with stage IA, IB or IIA CTCL [354836]. The FDA issued an approvable letter in June 2000, and granted marketing clearance for CTCL in the same month [370687], [372768], [372769], [373279]. Ligand had received Orphan Drug designation for this indication [329011]. At the request of the FDA, Ligand agreed to carry out certain post-approval phase IV and pharmacokinetic studies [351604]. The company filed an MAA with the EMEA for Targretin Capsules to treat lymphoma in November 1999 [348944]. The NDA for Targretin gel is based on a multicenter phase III trial that was conducted in the US, Canada, Europe and Australia involving 50 patients and a multicenter phase I/II clinical program involving 67 patients. Targretin gel was evaluated for the treatment of patients with early stage CTCL (IA-IIA) who were refractory to, intolerant to, or reached a response plateau for at least 6 months on at least two prior therapies. Efficacy results exceeded the protocol-defined response target rates; side effects were primarily limited to local skin reactions [349982]. Ligand has worldwide rights to market bexarotene capsules, and will market the drug in the US, Canada and selected European markets. In Spain, Portugal, Greece and Central and South America, Ferrer Internacional will market and distribute the drug. As of December 1999, Ligand was seeking additional distribution partners for select European and Asian markets [351604]. In January 2000, Alfa Wassermann signed an agreement with Ligand to exclusively market and distribute Targretin gel and capsules in Italy. Alfa paid US $0.75 million on signing with additional amounts up to an aggregate total of US $1.0 million on achievement of certain registration milestones, which are expected to be met in 2000 [351882].

Publication types

  • Review

MeSH terms

  • Animals
  • Anticarcinogenic Agents / adverse effects
  • Anticarcinogenic Agents / metabolism
  • Anticarcinogenic Agents / pharmacology*
  • Anticarcinogenic Agents / toxicity
  • Bexarotene
  • Clinical Trials as Topic
  • Contraindications
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / metabolism
  • Drugs, Investigational / pharmacology*
  • Drugs, Investigational / toxicity
  • Humans
  • Neoplasms / drug therapy*
  • Receptors, Retinoic Acid / antagonists & inhibitors*
  • Retinoid X Receptors
  • Structure-Activity Relationship
  • Tetrahydronaphthalenes / adverse effects
  • Tetrahydronaphthalenes / metabolism
  • Tetrahydronaphthalenes / pharmacology*
  • Tetrahydronaphthalenes / toxicity
  • Transcription Factors / antagonists & inhibitors*


  • Anticarcinogenic Agents
  • Drugs, Investigational
  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Tetrahydronaphthalenes
  • Transcription Factors
  • Bexarotene