Clinical studies

See the results

When put to the test, TARGRETIN delivered results for all stages of CTCL across 4 clinical studies.

Gel offers demonstrated efficacy across stages 1A and 1B

Phase III trial: 26% response rate with TARGRETIN Gel

TARGRETIN Gel produced an overall response rate of 26% (13/50) after 16 weeks of treatment by the Composite Assessment of Index Lesion Severity after 16 weeks of treatment.1

23% Relapse Rate
curly

The relapse rate in responding patients was 23% (3/13) over a median observation period of 149 days

2% (1/50) had a complete clinical response

For Stage IA and IB patients, the response rate was 28%

4 Weeks
Responses were seen as early as 4 weeks after starting treatment with TARGRETIN Gel1
85 Days
The median time to best response was 85 days after starting treatment1
Testing Equipment
The results of a Phase I-II program in 67 patients were supportive of these findings1
67 Patients

TARGRETIN Gel was also evaluated for the treatment of patients with CTCL in a Phase I-II program involving patients with early stage CTCL. This dose-seeking trial enrolled a total of 67 patients and featured different response criteria than the multicenter trial.

50 Patients

Targretin Gel was evaluated in a multicenter, open-label trial of 50 patients with early stage CTCL who had undergone and failed (i.e. were refractory to, intolerant to, or reached a plateau for) at least 2 prior therapies.

A Composite Assessment of Index Lesion Disease Severity was used to assess tumor response. This endpoint was based on summation of the grades for all the following index lesions:

  • Erythema
  • Scaling
  • Plaque elevation
  • Hypo- and hyperpigmentation
  • Area of involvement

New cutaneous lesions or tumors and extracutaneous disease manifestations were not considered in response or disease progression assessments.

Overall response included: Partial response was defined as an improvement of at least 50% in the index lesions without worsening or development of new cutaneous tumors or non-cutaneous manifestation. A complete clinical response required complete disappearance of the index lesions, but did not require confirmation by biopsy.

Capsules offer demonstrated efficacy across all stages of CTCL

Phase III trial: 32% response rate with TARGRETIN Capsules

TARGRETIN Capsules produced an overall response rate of 32% (20/62) by the Composite Assessment of Index Lesion Severity (CA) with 300 mg/m2/day.2

30% Relapse Rate
curly

The relapse rate in responding patients was 30% (6/20) over an observation period of 149 days

1.6% (1/62) had a complete clinical response

4 Weeks
Responses were seen as early as 4 weeks after starting treatment with TARGRETIN Capsules2
85 Days
The median time to best response was 85 days after starting treatment2

Phase IV trial: 35% response rate with TARGRETIN Capsules

In a post-approval clinical trial, response rate with 300 mg/m2/day was 35% vs 23.3% with 150 mg/m2/day with respect to CA.2

38% Relapse Rate
curly

The objective response rate with respect to Physician's Global Assessment was 37.9% with 300 mg/m2/day vs 20.0% with 150 mg/m2/day

The objective response rate with respect to BSA involvement was 34.5% with 300 mg/m2/day vs 23.3% with 150 mg/m2/day

4 Weeks
Responses were seen as early as 4 weeks after starting treatment with TARGRETIN Capsules2
85 Days
The median time to best response was 85 days after starting treatment2
152 Patients

TARGRETIN Capsules were evaluated in two multicenter, open-label, historically controlled clinical trials in 152 patients with advanced and early stage CTCL.

102 patients had disease refractory to at least 1 prior therapy. Of these:

  • 90 patients with advanced CTCL
  • 12 patients with early stage CTCL

A Composite Assessment of Index Lesion Disease Severity was used to assess tumor response. This endpoint was based on summation of the grades for all the following index lesions:

  • Erythema
  • Scaling
  • Plaque elevation
  • Hypo- and hyperpigmentation
  • Area of involvement

New cutaneous lesions or tumors and extracutaneous disease manifestations were not considered in response or disease progression assessments.

Overall response included: Partial response was defined as an improvement of at least 50% in the index lesions. A complete clinical response required complete disappearance of the index lesions, but did not require confirmation by biopsy.

2 Dose Levels

Targretin Capsules were evaluated in a multicenter, randomized, open-label, Phase IV study to determine the efficacy, tolerability, and safety of 2 initial dose levels in subjects with refractory CTCL.

The primary efficacy endpoints evaluated through 24 weeks of treatment were:

  • Cutaneous tumor responses determined by the Composite Assessment of Index Lesion Severity (CA) in 5 index lesions
  • Physician’s Global Assessment (PGA) of clinical condition
  • Percent BSA involvement with CTCL

For each primary endpoint, the response rate was defined as the sum of the percentage of subjects who achieved a complete response, clinical complete response, or partial response.

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IMPORTANT SAFETY INFORMATION AND INDICATIONS

Important Safety Information

WARNING: BIRTH DEFECTS

TARGRETIN capsules are a member of the retinoid class of drugs that is associated with birth defects in humans. Bexarotene also caused birth defects when administered orally to pregnant rats. TARGRETIN capsules must not be administered to a pregnant woman (8.1)

Contraindications

Both TARGRETIN capsules and TARGRETIN gel are contraindicated in women who are pregnant and in patients with a known hypersensitivity to bexarotene or other retinoids. If a woman becomes pregnant during treatment with TARGRETIN, treatment must be stopped immediately, and the woman provided appropriate counseling about the risks. See additional information below in Contraception, Pregnancy Testing and Nursing.

Contraception, Pregnancy Testing and Nursing

With both TARGRETIN capsules and TARGRETIN gel, to prevent pregnancy, effective contraception must be used for one month prior to the initiation of TARGRETIN therapy, during therapy and for at least one month following discontinuation of therapy; it is recommended that two reliable forms of contraception be used simultaneously unless abstinence is the chosen method. For TARGRETIN capsules, it is strongly recommended that one of the two reliable forms of contraception should be non-hormonal. Male patients with sexual partners who are pregnant, possibly pregnant or who could become pregnant must use condoms during treatment and for at least one month after the last dose of drug.

No more than a one-month supply of TARGRETIN should be given to the patient so that the results of pregnancy testing can be assessed and counseling regarding avoidance of pregnancy and birth defects can be reinforced.

For nursing women, a decision should be made whether to discontinue nursing or discontinue TARGRETIN gel, taking into account the importance of the drug to the mother. Because of the potential for serious adverse reactions in nursing infants from TARGRETIN capsules, discontinue breastfeeding during treatment with TARGRETIN capsules.

Warnings and Precautions
–   TARGRETIN capsules and TARGRETIN gel

Vitamin A Supplementation: Patients should be advised to limit Vitamin A intake to avoid potential additive toxicity.

Photosensitivity: Advise patients to minimize exposure to the sun and artificial sunlight during treatment.

Use on mucosal surfaces: Patients should be advised not to apply the gel on or near mucosal surfaces of the body such as eyes, nostrils, mouth, lips, vagina, tip of the penis, rectum, or anus.

Use of insect repellants: Advise patients using Targretin Gel to not concurrently use products that contain DEET.

–   TARGRETIN capsules

Hyperlipidemia is present in most patients treated with TARGRETIN capsules. Obtain baseline values, monitor during treatment, and manage elevations during therapy.

Acute pancreatitis, including a fatal case, has been reported in patients treated with TARGRETIN capsules. Interrupt treatment and evaluate if suspected.

Hepatotoxicity, cholestasis, and hepatic failure: TARGRETIN capsules had a dose-related effect on liver chemistry tests in clinical trials, including incidence of cholestasis and liver failure.

Hypothyroidism: TARGRETIN capsules induce hypothyroidism in about half of all patients; obtain baseline thyroid function tests. Monitor and replace thyroid hormone if needed during treatment.

Neutropenia: Leukopenia and neutropenia occurred in clinical trials with TARGRETIN capsules; obtain complete blood counts at baseline and periodically during treatment. Reduce TARGRETIN dose or interrupt as indicated.

Hypoglycemia in Patients with Diabetes: TARGRETIN capsules may cause hypoglycemia in patients using insulin, agents enhancing insulin secretions, or insulin-sensitizers.

Laboratory tests including CBC, fasting lipid profile, liver function tests, and thyroid profile should be obtained prior to and monitored during treatment.

CA125 assay values in ovarian cancer patients may be elevated by treatment with TARGRETIN capsules.

Cataracts: Although a causal relationship has not been established, cataracts have been observed in animal and clinical studies with TARGRETIN capsules. Refer patients who experience visual difficulties for ophthalmologic evaluation.

Adverse Reactions
–   TARGRETIN gel

The most common adverse reactions (≥10%) include rash, pruritus, pain, skin disorder (NOS), infection, contact dermatitis, headache, edema, hyperlipidemia.

–   TARGRETIN capsules

The most common adverse reactions (>10%) include hyperlipidemia, hypercholesteremia, headache, hypothyroidism, asthenia, leukopenia, rash, nausea, infection, peripheral edema, abdominal pain, and dry skin.

To report SUSPECTED ADVERSE REACTIONS contact customer service at 1-800-321-4576 or FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch

Please click here for full Prescribing Information, including Boxed Warning for TARGRETIN capsules

Please click here for full Prescribing information for TARGRETIN gel

Indications and Usage

TARGRETIN® (bexarotene) gel is indicated for the topical treatment of cutaneous lesions in patients with cutaneous T-cell lymphoma, CTCL (Stage 1A and 1B) who have refractory or persistent disease after other therapies or who have not tolerated other therapies. TARGRETIN® (bexarotene) capsules is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy.

References
  1. TARGRETIN gel 1% [prescribing information]. Bridgewater, NJ: Bausch Health US, LLC.
  2. TARGRETIN 75 mg capsules [prescribing information]. Bridgewater, NJ: Bausch Health US, LLC.

Important safety information

plus
Important Safety Information and Indications

WARNING: BIRTH DEFECTS

TARGRETIN capsules are a member of the retinoid class of drugs that is associated with birth defects in humans. Bexarotene also caused birth defects when administered orally to pregnant rats. TARGRETIN capsules must not be administered to a pregnant woman (8.1)

Indication and usage

TARGRETIN® (bexarotene) gel is indicated for the topical treatment of cutaneous lesions in patients with cutaneous T-cell lymphoma, CTCL (Stage 1A and 1B) who have refractory or persistent disease after other therapies or who have not tolerated other therapies. TARGRETIN® (bexarotene) capsules is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy.