Clinical Data

Ameluz® (aminolevulinic acid hydrochloride) gel, 10% a safe and effective AK treatment for your patients1

The efficacy and safety of Ameluz® using a narrow spectrum red light lamp were evaluated in randomized, double- and observer-blind and placebo-controlled trials (trials 1, 2, and 3), enrolling a total of 299 patients. Patients were adults, 49 years of age and older, with the majority skin type being Fitzpatrick I, II, or III, all Caucasian. No patient had Fitzpatrick skin type V or VI. Approximately 86% of patients were male. Trials 2 and 3 were vehicle-controlled and double-blind. Trial 1 was double-blind with respect to vehicle and observer-blind regarding an active comparator arm.

Results of three randomized, multi-centered clinical trials including 212 patients with 4 to 8 mild to moderate AK lesions on the face and/or scalp, treated with Ameluz® and a narrow band spectrum lamp; BF-RhodoLED® was used in trial 3. Patients were examined 12 weeks and 12 months after the last treatment, respectively (max. 2 PDTs).1

For all trials, the enrolled patients had mild to moderate AKs (Olsen grade 1 and 2) with 4 to 8 lesions on the face and scalp. Overall, 87 placebo-treated patients (n=16, n=32, n=39) and 212 Ameluz® -treated patients (n=32, n=55, and n=125) were illuminated with the BF-RhodoLED® or similar narrow spectrum lamps. All clinical trials included a follow-up assessment after 6 and 12 months.

Lesions that were not completely cleared 12 weeks after the initial treatment were treated a second time with an identical regimen. Overall, 58% (124/212) of patients did not need a second treatment. The primary endpoint for all trials was complete patient clearance 12 weeks after the last PDT (max. 2 PDTs). Patients who were completely cleared at 12 weeks after the last PDT entered the 12-month follow-up period.

In all three trials, patients who received Ameluz® with the narrow-band PDT and achieved complete clearance 12 weeks after the last PDT, had recurrence rates of 14%, 11%, and 25%, respectively (at 6 months) and 40%, 22%, and 37%, respectively (at 12 months). Recurrence was defined as the percentage of patients with at least one recurrent lesion during the 6-month or 12-month follow up period in patients with completely cleared lesions 12 weeks after the last PDT.

Trial 3: the first pivotal trial assessing safety and efficacy of field-directed PDT1

Trial 3 evaluated the combination of Ameluz® and BF-RhodoLED® in field-directed PDT. In this trial, 87 patients with 4-8 mild to moderate actinic keratoses on the face and scalp were treated with an entire tube of Ameluz and an application thickness of 1 mm. Illumination was performed with the BF-RhodoLED® lamp. The results were assessed 12 weeks after the last PDT (max. 2 PDTs). All patients treated within the scope of the trial were further monitored by the trial physicians for 12 months after the last treatment.

Trial 3 results demonstrated, that about six out of ten patients treated with Ameluz® and the BF-RhodoLED® did not require a second PDT. Together with the patients who received a second PDT, about 9 out of 10 patients were completely cleared of their AKs. Due to these results Ameluz® with the BF-RhodoLED® is the only PDT drug/device combination that has been approved for lesion-directed and field directed PDT.

  => 91% of patients were completely cleared of mild to moderate actinic keratosis (Olsen grade 1+2) on the face and scalp.

Total patient clearance rates during trial 3 including 87 patients with 4 to 8 mild to moderate AK lesions on the face and/or scalp, treated with Ameluz® and the BF-RhodoLED® lamp. Patients were examined 12 weeks and 12 months after the last treatment, respectively (max. 2 PDTs).1

62% of patients were completely cleared from all actinic keratoses already after the first treatment cycle with Ameluz® and BF-RhodoLED®.

63% of the completely cleared patients remain free of symptoms 12 months after the last treatment, with a recurrence rate of 37% (at 12 months).

Actinic keratoses on the scalp and moderate lesions (Olsen grade 2), which are more difficult to treat lesions, were also cleared effectively.

=> 89% of patients with moderate lesions (Olsen grade 2) and 82% with lesions on the scalp have been completely cleared.1

Difficult to treat: moderate lesions and lesions on the scalp are cleared with high efficacy rates using Ameluz® and BF-RhodoLED® (trial 3).1

Most frequent adverse reactions during and after PDT1

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Local skin reactions at the application site were observed in about 99.5% of patients treated with Ameluz® and narrow spectrum lamps. Most frequent adverse reactions included application site erythema, pain, burning, irritation, edema, pruritus, exfoliation, scab, induration, and vesicles.

Most adverse reactions occurred during illumination or shortly afterwards, were generally of mild to moderate intensity, and lasted for 1 to 4 days in most cases. In some cases, however, they persisted for 1 to 2 weeks or even longer. Severe pain/burning occurred in up to 30% of patients.

 

1 Ameluz® Prescribing Information. For Ameluz® full prescribing information and BF-RhodoLED® user manual please refer to: www.dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=650daa9f-aeec-49ce-95b9-5fa20b988afd

Important Safety Information

AMELUZ® (aminolevulinic acid hydrochloride) gel, 10% with BF-RhodoLED® lamp

AMELUZ®, containing 10% aminolevulinic acid hydrochloride, is a non-sterile gel formulation for topical use only. Not for ophthalmic, oral, or intravaginal use.

AMELUZ®, in conjunction with lesion preparation, is only to be administered by a health care provider. Photodynamic therapy with AMELUZ® involves preparation of lesions, application of the product, occlusion and illumination with BF-RhodoLED®. The application area should not exceed 20 cm2 and no more than 2 grams of AMELUZ® (one tube) should be used at one time. Lesions that have not completely resolved shall be retreated 3 months after the initial treatment. Refer to BF-RhodoLED® user manual for detailed lamp safety and operating instructions. Both patient and medical personnel conducting the PDT should adhere to all safety instructions.

Ameluz® shall not be used by persons who have known hypersensitivity to porphyrins or any of the components of AMELUZ®, which includes soybean phosphatidylcholine. Ameluz® should also not be used for patients who have porphyria or photodermatoses.

Transient Amnestic Episodes have been reported during postmarketing use of AMELUZ® in combination with photodynamic therapy (PDT). If patients experience amnesia or confusion, discontinue treatment. Advise them to contact the healthcare provider if the patient develops amnesia after treatment.

Eye exposure to the red light of the BF-RhodoLED® lamp during PDT must be prevented by protective eyewear. Direct staring into the light source must be avoided. AMELUZ® increases photosensitivity. Patients should avoid sunlight, prolonged or intense light (e.g., tanning beds, sun lamps) on lesions and surrounding skin treated with AMELUZ® for approximately 48 hours following treatment whether exposed to illumination or not.

AMELUZ® has not been tested on patients with inherited or acquired coagulation disorders. Special care should be taken to avoid bleeding during lesion preparation in such patients. Any bleeding must be stopped before application of the gel. AMELUZ® should not be used on mucous membranes or in the eyes.

Local skin reactions at the application site were observed in about 99.5% of subjects treated with AMELUZ® and narrow spectrum lamps. The very common adverse reactions (≥10%) during and after PDT were application site erythema, pain/burning, irritation, edema, pruritus, exfoliation, scab, induration, and vesicles. Most adverse reactions occurred during illumination or shortly afterwards, were generally of mild or moderate intensity, and lasted for 1 to 4 days in most cases; in some cases, however, they persisted for 1 to 2 weeks or even longer. Severe pain/burning occurred in up to 30% of treatments.

There have been no formal studies of the interaction of AMELUZ® with other drugs. Concomitant use of the following photosensitizing medications may increase the phototoxic reactions after PDT: St. John’s wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides, quinolones, and tetracyclines.

There are no available data on AMELUZ® use in pregnant women to inform a drug associated risk. No data are available regarding the presence of aminolevulinic acid in human milk, the effects of aminolevulinic acid on the breastfed infant or on milk production. Safety and effectiveness in pediatric patients below the age of 18 have not been established as AK is not a condition generally seen in the pediatric population. No overall differences in safety or effectiveness were observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Please read the US Full Prescribing Information for Ameluz® and/or US User Manual of BF-RhodoLED® lamp available together at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=650daa9f-aeec-49ce-95b9-5fa20b988afd.

You are encouraged to report side effects of Ameluz®. Please contact Biofrontera Inc. at 1-844-829-7434 or FDA at 1-800-332-1088 or www.fda.gov/medwatch.