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  5. Drug Trials Snapshot: KLISYRI
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Drug Trials Snapshot: KLISYRI

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the KLISYRI Package Insert for complete information.

KLISYRI (tirbanibulin)
(klye si' ree )
Almirall, LLC
Approval date: December 14, 2020

DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

KLISYRI is used on the skin to treat patients with actinic keratosis on the face or scalp.

Actinic keratosis is a common skin disease caused by long-term exposure to the sun and/or indoor tanning. If left untreated, AK may progress to skin cancer.

How is this drug used?

KLISYRI is an ointment. One package of ointment is applied on the affected area of face or scalp 1 time a day for 5 days in a row.

What are the benefits of this drug?

More patients achieved complete clearance of AK after 5 days of treatment with KLISYRI in comparison to those who were treated with control ointment (vehicle).

What are the benefits of this drug (results of trials used to assess efficacy)?

The table below summarizes efficacy results for the evaluated patients in Trials 1 and 2. The primary efficacy endpoint was complete (100%) clearance of AK lesions in the treatment area, defined as the proportion of subjects at Day 57 with no clinically visible AK lesions in the treatment area.

Table 1. Complete (100%) AK Clearance Rates on Day 57 for the Two Phase 3 Studies (Intent to Treat [ITT] Population

 

Trial 1

Trial 2

 

KLISYRI
N = 175
n/N (%)

Vehicle
N = 176
n/N (%)

Treatment difference
(KLISYRI-Vehicle)

95% Confidence Interval
for the Treatment difference

KLISYRI
N = 178
n/N (%)

Vehicle
N = 173
n/N (%)

Treatment difference
(KLISYRI-Vehicle)

95% Confidence Interval
for the Treatment difference

All patients

77/175

(44%)

8/176

(5%)

40%a

(31.6%, 47.5%)a

97/178

(54%)

22/173 (13%)

42%a

(33.1%, 50.7%)a

Face

60/119

(50%)

7/121

(6%)

45%

--

73/119

(61%)

16/118 (14%)

48%

--

Scalp

17/56

(30%)

1/55

(2%)

29%

--

24/59

(41%)

6/55

(11%)

30%

--

a Based on Mantel-Haenszel method

KLISYRI Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

  • Sex: Almost all patients in the trials were men, therefore differences in how KLISYRI worked between men and women could not be determined.
  • Race: Almost all patients in the trials were White therefore, differences in how KLISYRI worked among races could not be determined.
  • Age: KLISYRI worked similarly between patients younger than and older than 65 years of age.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The tables below summarize efficacy results by sex, and age in individual trials

Table 2. Complete (100%) Clearance Rates at Day 57 in for Subgroups Based on Sex and Age for Trial 1

 

Trial 1

KLISYRI
(N=175)

Vehicle
(N=176)

Difference and 95% CI
for Difference1

Sex

  Women, n/N (%)

17/28 (60.7%)

3/22 (13.6%)

47.1%

(20.1%,68.9%)

  Men, n/N (%)

60/147 (40.8%)

5/154 (3.3%)

37.6%

(26.7%,47.8%)

Age

  <65 years, n/N (%)

23/51 (45.1%)

1/42 (2.4%)

42.7%

(23.0%, 59.9%)

  ≥ 65 years, n/N (%)

54/124 (43.6%)

7/134 (5.2%)

38.3%

(26.6%,49.2%)

Table 3. Complete (100%) Clearance Rates at Day 57 in for Subgroups Based on Sex and Age for Trial 2

 

Trial 2

KLISYRI
(N=178)

Vehicle
(N=173)

Difference and 95% CI
for Difference1

Sex

  Women, n/N (%)

17/20 (85.0%)

3/23 (13.0%)

72.0%

(45.2%,88.9%)

  Men, n/N (%)

80/158 (50.6%)

19/150 (12.7%)

38.0%

(27.2%,48.0%)

Age

  <65 years, n/N (%)

35/56 (62.5%)

4/39 (10.3%)

52.2%

(33.4%,68.1%)

  ≥ 65 years, n/N (%)

62/122 (50.8%)

18/134 (13.4%)

37.4%

(25.6%,48.3%)

Note: Complete (100%) clearance rate was defined as the proportion of subjects with no clinically visible AK lesions in the treatment area at Day 57.
1 Based on Clopper-Pearson Exact 95% CI. Note that for subgroup face and scalp, the reported 95% CI is for exploratory rather than confirmatory purpose
Adapted from FDA Review

What are the possible side effects?

KLISYRI may cause eye irritation.

The most common side effect of KLISYRI are local skin reactions, application site pruritus, and application site pain.

What are the possible side effects (results of trials used to assess safety)?

Presented below are common adverse reactions in the pooled trials.

Table 4. Adverse Reactions Occurring in ≥2% of Subjects in 2 Controlled Clinical Trials– Pooled Safety Population

Adverse Reaction
   System Organ Class

KLISYRI
N = 353

Vehicle
N = 349

Number of Patients (%) with any adverse reaction

(possibly related to treatment)

56 (16%)

35 (10%)

   Application site pruritus

32 (9%)

21 (6%)

   Application site paina

35 (10%)

11 (3%)

a Application site pain includes pain, tenderness, stinging, and burning sensation at the application site.
KLISYRI Prescribing Information

Were there any differences in side effects among sex, race and age?

  • Sex: Almost all patients in the trials were men, therefore differences in the occurrence of side effects between men and women could not be determined.
  • Race: Almost all patients in the trials were White, therefore differences in the occurrence of side effects among races could not be determined.
  • Age: The occurrence of side effects was similar between patients younger than and older than 65 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The tables below summarize the occurrence of the most common adverse reactions, by sex and age subgroups.

Table 5. Subgroup Analysis of Common Adverse Reactions by Sex

 

KLISYRI (N=175)

Vehicle (N=176)

Women
n/N (%)

Men
n/N (%)

Women
n/N (%)

Men
n/N (%)

Application Site Pruritis

6/48 (13)

26/305 (9)

1/45 (2)

20/304 (7)

Application Site Pain

5/48 (10)

30/305 (10)

0/45 (0)

11/304 (4)

Table 6. Subgroup Analysis of Common Adverse Reactions by Age

 

KLISYRI (N=175)

Vehicle (N=176)

<65 years
n/N (%)

≥ 65 years
n/N (%)

<65 years
n/N (%)

≥ 65 years
n/N (%)

Application Site Pruritis

10/107 (9)

22/246 (9)

4/81 (5)

17/268 (6)

Application Site Pain

12/107 (11)

23/246 (9)

3/81 (4)

8/268 (3)

Clinical Trial Data

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved KLISYRI based on evidence from two clinical trials (Trial 1/ NCT0328547 and Trial 2/03285490) of 702 adult patients with actinic keratosis on the face or scalp. The trials were conducted at 62 sites in the United States.

Figure 1 summarizes how many men and women were in the clinical trials.

Figure 1. Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trials. In total, 609 men (87%) and 93 women (13%) participated in the clinical trial.

FDA Review

Figure 2 summarizes the percentage of patients by race in the clinical trials.

Figure 2. Demographics by Race

Pie chart summarizing how many patients of different races were in the clinical trial reported. In total, 700 patients were White (99%) and 2 patients were American Indian or Alaska Native (1%).

FDA Review

Figure 3 summarizes the percentage of patients by age in the clinical trials.

Figure 3. Demographics by Age

Pie chart summarizing how many individuals of certain age groups were in the clinical trial. In total, 188 patients were less than 65 years old (27%) and 514 patients were 65 years and older (73%).

FDA Review

Figure 4 summarizes the percentage of patients by ethnicity in the clinical trials.

Figure 4. Demographics by Ethnicity

Pie chart summarizing how many individuals of certain ethnicity groups were in the clinical trial. In total, 26 patients were Hispanic or Latino (4%) and 676 patients were not Hispanic or Latino (96%).

FDA Review

Who participated in the trials?

The table below summarizes demographics of the population in the trials.

Table 7. Baseline Demographics

 

Trial 1
N=351

Trial 2
N=351

Total
N=702

Sex, n (%)

    Men

301 (86)

308 (88)

609 (87)

    Women

50 (14)

43 (12)

93 (13)

Race, n (%)

    White

350 (>99)

350 (>99)

700 (>99)

    American Indian or Alaska Native

1 (<1)

1 (<1)

2 (<1)

Age (years)

    Median

70.0

70.0

70.0

    Min, max

45, 97

47, 93

45, 97

Age group (years), n (%)

    <65

93 (26)

95 (27)

188 (27)

    ≥65

258 (74)

256 (73)

514 (73)

Ethnicity, n (%)

    Hispanic or Latino

7 (2)

19 (5)

26 (4)

    Not Hispanic or Latino

344 (98%)

332 (95)

676 (96)

Region

    USA

351 (100)

351 (100)

702 (100)

FDA Review

How were the trials designed?

The benefit and side effects of KLISYRI were evaluated in two clinical trials which enrolled adult patients with actinic keratosis on the face or scalp.

Patients received once daily treatment with either KLISYRI or inactive control ointment for 5 consecutive days to the single predetermined area where they had actinic keratosis. Neither the patients nor the health care providers knew which treatment was being given until after the trial was completed.

The benefit of KLISYRI in comparison to control was assessed after 57 days by comparing the percentage of patients who did not have any AK on the treatment area (100% clearance).

How were the trials designed?

The safety and efficacy of KLISYRI were established in two double-blind, vehicle-controlled clinical trials that enrolled adult patients with actinic keratosis on the face or scalp. Patients had 4 to 8 clinically typical, visible, and discrete AK lesions in a contiguous area of 25 cm2 on the face or scalp.

Patients received 5 consecutive days of once daily treatment with either KLISYRI or vehicle control to the treatment field.

The primary efficacy endpoint was complete (100%) clearance of AK lesions in the treatment area, defined as the proportion of patients at Day 57 with no clinically visible AK lesions in the treatment area.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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