STYLE

Otezla Is the Only Oral Therapy With Scalp Data in Its label ²

CHAPTER 1

Thank you for joining us. Please see Important Safety Information during this video and the full Prescribing Information on OtezlaPro.com. Hi, my name is Jennifer Cather, and I’m a dermatologist at Mindful Dermatology in Dallas, Texas. Today I’ll be speaking on behalf of Amgen about Otezla, also known as apremilast. Otezla is a non-biologic, phosphodiesterase 4 inhibitor indicated for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. Otezla is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation. With an FDA-approved label expansion in April 2020, Otezla is the first and only oral therapy with data in the label for moderate to severe scalp psoriasis. Today we’ll review these data in detail. But first, let’s review the warnings and precautions associated with the use of Otezla. It’s important to note that cases of severe diarrhea, nausea, and vomiting have been reported with the use of Otezla. However, most events occurred within the first few weeks of treatment. In some cases patients were hospitalized. We should be mindful that patients 65 years of age or older and patients taking medications that can lead to volume depletion or hypotension may be at a higher risk of complications from severe diarrhea, nausea, or vomiting. Additionally, we should monitor patients who are more susceptible to complications of diarrhea or vomiting, and advise patients to contact their healthcare provider. Otezla dose reduction or suspension should be considered if patients develop severe diarrhea, nausea, or vomiting. Before we dive into the clinical trial for moderate to severe psoriasis of the scalp, let’s briefly review one of the two registrational trials for moderate to severe plaque psoriasis, ESTEEM® 1. ESTEEM® 1 was a Phase 3, randomized, placebo-controlled trial that enrolled 844 adult patients with moderate to severe plaque psoriasis. Patients were randomized 2:1 to receive Otezla 30 milligrams twice daily or placebo up to week 16. ^1-3 Selected inclusion criteria for the study include an sPGA of at least 3, indicative of moderate to severe disease, as well as BSA involvement of at least 10%, and a PASI score of at least 12. Patients were also candidates for phototherapy or systemic therapy. ^1,2 The primary endpoint of the study was the proportion of patients achieving a PASI-75, or 75% clearer skin, at week 16. ^1,2 Here, we can see the primary endpoint was achieved in the ESTEEM® 1 trial. ^1,2 Otezla treatment resulted in significantly more patients achieving a PASI-75 response at week 16, compared with placebo. ^1-3 Specifically, a total of 33% of patients on Otezla achieved a response versus 5% of patients on placebo. ^1,2 Another important safety matter related to the use of Otezla is depression. Treatment with Otezla is associated with an increase in depression, with 1.3% of patients reporting symptoms compared with 0.4% on placebo during clinical trials. Suicidal behavior was observed in 0.1% of patients on Otezla, compared to 0.2% on placebo. When prescribing Otezla, we need to carefully weigh the risks and benefits of treatment with Otezla for patients with a history of depression and/or suicidal thoughts or behaviors, or in patients who develop such symptoms while on Otezla. Patients, caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal thoughts, or other mood changes, and they should contact their healthcare provider if they notice such changes. Now let’s review the STYLE clinical trial, which evaluated the efficacy and safety of Otezla for adult patients with moderate to severe plaque psoriasis of the scalp. STYLE was a Phase 3, randomized, double blind, placebo-controlled trial that enrolled a total of 303 adult patients with moderate to severe scalp psoriasis. Patients were randomized 2:1 to receive either Otezla or placebo for 16 weeks. The open-label extension phase lasted from week 16 to week 32. During this phase, patients in the placebo arm were switched to Otezla, and patients randomized to Otezla at baseline continued with treatment. The primary endpoint of the STYLE trial was the proportion of patients at week 16 who achieved a Scalp Physician’s Global Assessment response, or scalp PGA, score of 0, indicating clear skin, or 1, indicating almost clear skin, with at least a 2-point reduction from baseline. To be included in the study, patients were adults aged 18 years or more, with both moderate to severe plaque psoriasis and moderate to severe scalp psoriasis. Specifically, moderate to severe psoriasis was defined as a BSA involvement of at least 10%, an sPGA of at least 3, and a PASI score of at least 12, while moderate to severe scalp psoriasis was defined as a scalp PGA of at least 3 and a scalp surface area of at least 20. Patients were also candidates for phototherapy or systemic therapy. At baseline, all patients in STYLE had moderate or severe scalp psoriasis. ^3,4 Specifically, 76.1% of patients had moderate scalp psoriasis as indicated by a scalp PGA score of 3, while 23.1% of patients had severe scalp psoriasis, as indicated by a scalp PGA of 4. ^3,4 The primary endpoint in STYLE was achieved with Otezla treatment, resulting in significantly more patients achieving a scalp PGA response at week 16 compared with placebo. Specifically, 43.3% of patients on Otezla achieved a response versus 13.7% of patients on placebo. If you’re interested in learning about the scalp PGA response at a longer time point, be sure to click on the appropriate link at the end of this presentation. Here we see an example of results in a scalp psoriasis patient from the STYLE trial. While individual results may vary, in this case we see a scalp PGA score of 0 with a 3-point improvement from baseline at 16 weeks with Otezla. Other warnings and precautions for the use of Otezla include weight decrease and drug interactions. A body weight loss of 5 to 10 percent occurred in 12% of patients treated with Otezla and in 5% of patients treated with placebo. Therefore, we should monitor body weight regularly, evaluate unexplained or clinically significant weight loss, and consider discontinuation of Otezla. In terms of drug interactions, apremilast exposure was decreased when Otezla was co-administered with rifampin, a strong CYP450 enzyme inducer, indicating loss of Otezla efficacy may occur. Additionally, concomitant use of Otezla with CYP450 enzyme inducers is not recommended. Now let’s review in more detail the safety data from the Otezla clinical trials. Adverse reactions reported in at least 5% of patients in 3 clinical trials, including ESTEEM®, were diarrhea, nausea, upper respiratory tract infection, tension headache, and headache. The most common adverse reactions observed in the STYLE trial that were reported in at least 5% of patients taking Otezla were diarrhea, nausea, headache, and vomiting. ^1,4 Discontinuation of treatment due to any adverse reaction during the placebo-controlled period was 6% for patients taking Otezla and 3% for placebo. ¹ Discontinuation rates due to diarrhea, nausea, or vomiting in patients who received Otezla versus placebo were 3% versus 0% for diarrhea, 1.5% versus 1% for nausea, and 1.5% versus 0% for vomiting, respectively. ¹ Here we can see selected marked abnormalities in laboratory parameters as assessed in the ESTEEM trials. ³

Please note, the Prescribing Information for Otezla has no requirement for baseline or routine lab monitoring. ¹ When prescribing Otezla, it’s important to note that Otezla has not been studied in pregnant women. Advise pregnant women of the potential risk of fetal loss, and consider pregnancy planning and prevention for females of reproductive potential. Note that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Otezla during pregnancy. Information about the registry can be obtained by calling the phone number listed on the slide, or visiting the MotherToBaby.org website. Additionally, there are no data on the presence of apremilast or its metabolites in human milk, the effects of apremilast on the breastfed infant, or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Otezla and any potential adverse effects on the breastfed child from Otezla or from the underlying maternal condition. The dosage of Otezla should be reduced to 30 milligrams once daily in patients with severe renal impairment, as defined by a creatinine clearance of less than 30 milliliters per minute. For details, please see additional Safety Information included in this video and the full Prescribing Information provided on OtezlaPro.com. So to summarize some key facts about Otezla, first, there is no requirement for routine laboratory monitoring from the Prescribing Information. ¹ Additionally, regarding safety, it’s important to remember that in the psoriasis trials, the majority of patients reporting nausea and diarrhea did so within the first 2 weeks, and the events tended to resolve over time with continued dosing. ³ Postmarketing reports of severe diarrhea, nausea, and vomiting have been associated with the use of Otezla, and in some cases patients were hospitalized, so patients who are more susceptible to complications of diarrhea or vomiting should be monitored. ¹ As the data from the STYLE trial that we reviewed today were included in the label expansion, Otezla is the only oral therapy with data in the label for moderate to severe scalp psoriasis. ¹ And lastly, with an FDA approval in March 2014, Otezla has been on the market for 6 full years. ¹ Thank you for listening. Click one of these options to learn more about the STYLE trial and Otezla.

References: 1. Otezla [package insert]. Thousand Oaks, CA: Amgen, Inc. 2. Papp K, Reich K, Leonardi CL, et al. J Am Acad Dermatol. 2015;73:37-49. 3. Data on file, Amgen Inc. 4. Van Voorhees A, Gold LS, Lebwohl M, et al. J Am Acad Dermatol. 2020;83(1):96-103.

CHAPTER 2

Hello again. To briefly review what we’ve learned so far, the STYLE clinical trial was a Phase 3, multicenter, randomized, double-blind, and placebo-controlled study that evaluated the efficacy and safety of Otezla in patients with moderate to severe plaque psoriasis of the scalp. In the placebo-controlled phase, patients were randomized 2:1 and were administered Otezla 30 milligrams twice daily or placebo for 16 weeks. The primary endpoint was the proportion of patients who achieved a scalp PGA response of 0, indicating clear skin, or 1, indicating almost clear skin, with at least a 2-point reduction from baseline after 16 weeks of treatment. As we’ve already reviewed, this primary endpoint was achieved as analyzed using a multiple imputation analysis. Week 16 to week 32 of the trial comprised the open-label extension phase, where at week 16 patients in the placebo arm were switched to Otezla, and patients initiated on Otezla continued treatment for another 16 weeks. All data in the open-label extension phase were analyzed using a non-responder imputation, or NRI, analysis. Here we can see the results from the open-label extension phase of the study. Keep in mind that this phase was not blinded and not controlled, and included inherent self-selection bias for remaining in the trial. In this exploratory NRI analysis, the percentage of patients achieving a scalp PGA response at week 16 was 38.8% for Otezla versus 10.8% for placebo. ^1-3 At week 32, a total of 44.8% of patients who started on Otezla and 60.7% of patients who switched to Otezla achieved a scalp PGA response. ^1-3 In the STYLE clinical trial, the most common adverse reactions reported in at least 5% of patients taking Otezla include diarrhea, nausea, headache, and vomiting. ^1,2 Discontinuation of treatment due to any adverse reaction during the placebo-controlled period was 6% for patients taking Otezla and 3% for placebo. ¹ Specifically, discontinuation rates due to diarrhea, nausea, or vomiting in patients who received Otezla vs placebo were 3% versus 0% for diarrhea, 1.5% versus 1% for nausea, and 1.5% versus 0% for vomiting, respectively. ¹ During the open-label extension phase, discontinuation due to an adverse reaction was 3.0% for patients remaining on Otezla and 1.2% for patients who switched to Otezla. This chart shows the adverse reactions reported in at least 2% of patients in any treatment group during the open-label extension phase from weeks 16 to 32. The most common adverse reactions in patients who remained on Otezla were nausea, nasopharyngitis, and urinary tract infection. For patients who switched to Otezla, the most common adverse reactions were diarrhea and nausea. Here, we can see an example from a patient treated with Otezla in the STYLE trial. While individual results may vary, in this case we see a scalp PGA score of 3 with a 1-point improvement from baseline at 16 weeks with Otezla. Here’s another example of results from a different patient treated with Otezla at both week 16 and at week 32.

While individual results may vary, in this case we see a scalp PGA score of 2 with a 1-point improvement from baseline at 16 weeks with Otezla, and a scalp PGA score of 1 with a 2-point improvement from baseline at 32 weeks with Otezla. So to summarize, the STYLE clinical trial provided scalp PGA responses for up to 32 weeks as part of the exploratory open-label extension phase. ^1,2 The most common adverse reactions in the STYLE trial were diarrhea, nausea, headache, and vomiting. ¹ Notably, Otezla is the only oral therapy with data in the label for moderate to severe scalp psoriasis. ¹ Thank you for listening. Click on one of these buttons to learn more about the STYLE trial and Otezla.

References: 1. Otezla [package insert]. Thousand Oaks, CA: Amgen, Inc. 2. Van Voorhees A, Gold LS, Lebwohl M, et al. J Am Acad Dermatol. 2020. 3. Data on file, Amgen Inc.

CHAPTER 3

Hello again. To recap what we’ve learned so far, the STYLE clinical trial was a Phase 3, randomized, double-blind, placebo-controlled study of adult patients that evaluated the efficacy and safety of Otezla in patients with moderate to severe plaque psoriasis of the scalp. Patients were randomized 2:1 and were administered Otezla 30 milligrams twice daily or placebo for 16 weeks. During the open-label extension phase, at week 16, patients in the placebo arm were switched to Otezla and patients initiated on Otezla continued treatment for another 16 weeks. As we’ve already reviewed, the primary endpoint of the proportion of patients who achieved a scalp PGA response of 0 or 1 at week 16 was achieved. Let’s now review selected secondary endpoints, namely the proportion of patients with at least a 4-point reduction from baseline in scalp itch and whole body itch as measured by the numeric rating scale, or NRS, at weeks 2, 4, 8, 12, and 16 and analyzed by a multiple imputation analysis. For scalp itch, Otezla treatment resulted in significantly more patients achieving at least a 4-point improvement from baseline in scalp itch NRS score at week 16 compared with placebo, with 47.1% of patients on Otezla achieving a response versus 21.1% of patients on placebo. ^1-3 Notably, a significant improvement in scalp itch was seen as early as 2 weeks with Otezla treatment. At the 2-week mark, 26.1% of patients on Otezla achieved a scalp itch response versus 11.5% of patients on placebo. ^1-3 Here we can see the scalp itch responses from the open-label extension phase of the study, which was analyzed using an NRI analysis. Keep in mind that this open-label extension phase was not blinded, not controlled, and included inherent self-selection bias for remaining in the trial. In this exploratory NRI analysis, the percentage of patients achieving a scalp itch response at week 16 was 40.0% with Otezla versus 15.6% for placebo. ^1-3 Then, at week 32, approximately 47% of patients who started on Otezla and of patients who switched to Otezla achieved a scalp itch response. ^1-3 We also see a significant improvement in whole body itch with Otezla treatment, as after 16 weeks of treatment, 45.5% of patients on Otezla achieved at least a 4-point improvement from baseline in whole body itch NRS score as compared with 22.5% of patients on placebo. ^1-3 Notably, a significant improvement in whole body itch was also seen as early as 2 weeks with Otezla treatment, with 20.5% of patients on Otezla achieving a whole body itch response versus 3.5% of patients on placebo. ^1-3 In the open-label extension phase, the percentage of patients achieving a whole body itch response at week 16 was 40.0% with Otezla versus 19.1% for placebo, as analyzed using an NRI analysis. ^1-3 Then, at week 32, approximately 45% of patients who started on Otezla and 57.1% of patients who switched to Otezla achieved a whole body itch response. ^1-3 As I mentioned previously, keep in mind that the open-label extension phase was not blinded and not controlled, and included inherent self-selection bias for remaining in the trial. In the STYLE clinical trial, the most common adverse reactions reported in at least 5% of patients taking Otezla include diarrhea, nausea, headache, and vomiting. ^1,2 Discontinuation of treatment due to any adverse reaction during the placebo-controlled period was 6% for patients taking Otezla and 3% for placebo. ¹ Specifically, discontinuation rates due to diarrhea, nausea, or vomiting in patients who received Otezla versus placebo were 3% versus 0% for diarrhea, 1.5% versus 1% for nausea, and 1.5% versus 0% for vomiting, respectively. ¹ During the open-label extension phase, discontinuation due to an adverse reaction was 3.0% for patients remaining on Otezla and 1.2% for patients who switched to Otezla. This chart shows the adverse reactions reported in at least 2% of patients in any treatment group during the open-label extension phase from weeks 16 to 32. The most common adverse reactions in patients who remained on Otezla were nausea, nasopharyngitis, and urinary tract infection. For patients who switched to Otezla, the most common adverse reactions were diarrhea and nausea. In summary, 16 weeks of Otezla treatment showed significant improvement in scalp and whole body itch, with a significant improvement seen as early as 2 weeks. ^1,2 The most common adverse reactions in the STYLE trial were diarrhea, nausea, headache, and vomiting. ² The week 16 data from the STYLE trial that we reviewed today were included in the label expansion for Otezla, making it the only oral therapy with data in the label for moderate to severe scalp psoriasis. ¹ Thank you for listening. Click on one of these buttons to learn more about the STYLE trial and Otezla.

References: 1. Otezla [package insert]. Thousand Oaks, CA: Amgen, Inc. 2. Van Voorhees A, Gold LS, Lebwohl M, et al. J Am Acad Dermatol. 2020. 3. Data on file, Amgen Inc.