Almirall’s Klisyri Gets FDA Approval for AKs
The FDA has approved Almirall’s Klisyri (tirbanibulin) for the topical treatment of actinic keratosis (AK) of the face or scalp. Klisyri, a novel, topical first-in-class microtubule inhibitor with a short treatment protocol (once daily application for five days), and proven efficacy and safety profile, is expected to be available in the first quarter of 2021.
With a reported prevalence of between 11 and 25 percent, actinic keratosis is the second most common diagnosis made by dermatologists in the US.
FDA approval of Klisyri is based on data from one of the largest Phase 3 clinical study programs ever conducted for a topical AK treatment. The program consisted of two pivotal, randomized, double-blind, vehicle-controlled Phase 3 studies (KX01-AK-003 and KX01-AK-004) that evaluated the efficacy and safety of tirbanibulin ointment 1% in adults with actinic keratosis on the face or scalp.
“These studies enrolled a total of 702 patients across 62 sites in the United States, providing robust data. Tirbanibulin achieved a significantly higher number of patients with complete (100 percent) clearance of AK lesions in the treated area compared to vehicle (44 vs. 5 percent in study 1 and 54 vs. 13 percent in study 2), as well as reaching the secondary endpoint of partial (≥75 percent) clearance of lesions,” says Andrew Blauvelt, MD, MBA, President of Oregon Medical Research Center, and one of the lead investigators of the studies.
AbbVie’s Rinvoq Performs Well in Head-to-Head Phase 3b AD Study
Topline results from the Phase 3b “Heads Up” study show that a greater proportion of subjects treated with AbbVie’s Rinvoq (upadacitinib 30mg, once daily) achieved at least a 75 percent improvement in the Eczema Area Severity Index (EASI 75) at week 16, compared to dupilumab (300mg, every other week). EASI 75 was the primary endpoint in the study in adults with moderate to severe atopic dermatitis.
Seventy one percent of upadacitinib-treated subjects achieved EASI 75 at week 16, compared to 61 percent of dupilumab-treated patients. AbbVie says upadacitinib showed superiority to dupilumab for all ranked secondary endpoints, including additional measures of skin clearance and itch reduction. Patients were randomized to receive upadacitinib or dupilumab, both as monotherapy treatments, for 24 weeks.
Rinvoq is not FDA approved for AD. Dupixent is the only approved systemic treatment for AD that has been studied for up to three years in a Phase 3 trial of adults.
Results of ranked secondary endpoints showed higher efficacy in early improvements of itch and skin clearance.
Patients treated with upadacitinib had a 31 percent reduction in itch (as measured by Worst Pruritus Numerical Rating Scale [NRS]), compared to nine percent in the dupilumab group. Itch improvements were maintained through week 16. Additionally, 44 percent of upadacitinib-treated patients achieved EASI 75 response at week two, versus 18 percent of dupilumab-treated patients.
The safety profile of upadacitinib was consistent with that observed in the Phase 3 pivotal studies, Measure Up 1, Measure Up 2, and AD Up. Through week 16, the most common adverse events were acne for the upadacitinib group and conjunctivitis for the dupilumab group. Serious adverse events occurred in 2.9 percent of patients receiving upadacitinib and 1.2 percent of patients receiving dupilumab. Serious infections were reported infrequently in both treatment groups (1.1 percent in patients who received upadacitinib and 0.6 percent in patients who received dupilumab). One treatment-emergent death due to bronchopneumonia associated with influenza A occurred in a patient who received upadacitinib. No malignancies were reported in the upadacitinib group; one non-melanoma skin cancer was reported in the dupilumab group. No major adverse cardiac events or venous thromboembolic events were reported in either treatment group.
Take 5 with Camille Lee, Head of Immunology, UCB, U.S.
2020 was a challenging year for many, including those in the dermatology industry. Camille Lee, Head of Immunology at UCB, US recently spoke to Practical Dermatology® about any challenges the company faced due to the COVID-19 pandemic and how the company continues to maintain support of the field and practitioners and patients.
1. Pivoting in the Pandemic
Ms. Lee: Throughout the pandemic, UCB has continued delivering investigational treatment for patients by transitioning our clinical trials to a virtual format and implementing remote site monitoring.
In March of 2020, during a time of extraordinary medical emergency, the evolving COVID-19 pandemic led UCB to halt recruitment into ongoing clinical studies and delay all new study starts. This decision was taken in the interest of public health safety and to help reduce the strain on healthcare systems across the world.
2. Adapting and Moving Forward
Ms. Lee: In mid-May, we began to restart clinical study recruitment, including new study starts, at clinical trials sites that met our restart criteria. We continue to proactively monitor the COVID-19 situation and will take any necessary precautionary steps in the interest of public health.
3. Keeping Priorities Straight
Ms. Lee: During this challenging time the health and safety of patients, HCPs and employees are our top priorities. As communities and practices across the US navigate the ongoing pandemic, we have evolved our day-to-day operations, engagement with physicians and support resources to meet the needs of patients and HCPs at this time.
4. Remaining Reliable
Ms. Lee: Amidst this transition, UCB remains a reliable partner for healthcare professionals—a resource that the dermatology community can rely on.
5. Committed to Collaboration
Ms. Lee: UCB is aware of the strain COVID-19 has placed on healthcare providers and we’re committed to playing our part in supporting those impacted in these uncertain times. At UCB, this includes making ongoing adjustments to our patient assistance and educational programs to support continued access for patients who are prescribed UCB medications. We also remain committed to collaborating with the medical community to share clinical knowledge and provide educational resources to support optimal patient outcomes.
Hydrafacial To Go Public After $1.1 Billion Deal
The HydraFacial Company and Vesper Healthcare, a special purpose acquisition company (SPAC) co-founded by Brent Saunders, former CEO of Allergan, have entered into a definitive merger agreement.
Under the terms, HydraFacial and Vesper Healthcare will combine, and HydraFacial will become a public company. Upon completion of the transaction, the combined company expects to be listed on the NASDAQ exchange. The transaction is valued at a pro forma enterprise value of $1.1 billion. The purchase price consists of $975 million payable at closing and up to $75 million payable upon the completion of certain identified acquisitions by the combined company
HydraFacial’s senior management will continue to serve in their current roles upon the closing of the proposed transaction. HydraFacial will continue to be led by CEO Clint Carnell. Liyuan Woo will continue as CFO. Brent Saunders, CEO of Vesper Healthcare will serve as Executive Chairman. Manisha Narasimhan, PhD, CFO of Vesper Healthcare, will join HydraFacial as Chief Strategy Officer.
“We have a proven track record of growth in a large and growing market, we have developed a critical mass globally with over 15,000 delivery systems in operation and our business model provides us with a recurring revenue stream in consumables,” says Clint Carnell, HydraFacial CEO. “This, along with favorable demographic trends, supported by our experienced team which has been made even stronger by combining with Vesper Healthcare, has created a business model that we believe is well positioned to deliver sustained long-term growth. We plan to leverage our infrastructure to bring to market additional innovative products backed by powerful technology. I am honored to partner with Brent and Manisha and look forward to benefiting from their insights as we embark on this new chapter.”
Brent Saunders, CEO and co-founder of Vesper Healthcare, adds, “This is a significant day for Vesper Healthcare and HydraFacial as we team up with a category-creating company in the emerging area of beauty health. Our goal is to build a premier company in beauty health, focused on providers such as estheticians and nurse practitioners, consumers, and partners and we believe that HydraFacial is the perfect platform to achieve this goal. HydraFacial possesses industry-leading consumer satisfaction scores and has presence in two high-growth categories within personal care – skincare and, more recently, hair care. We look forward to working with the HydraFacial team to create a valuable, industry-leading, global company in beauty health.”
Gene Sequencing May Quantify Risk of Skin Cancer Long Before Damage is Visible
In a study published in Science Advances, researchers detail a method to measure the abundance of cancer-related early changes to skin tissue long before the damage becomes visible to the eye.
Led by a multidisciplinary team from Roswell Park’s Dermatology, Biostatistics and Bioinformatics and Pharmacology and Therapeutics departments—Lei Wei, PhD, Barbara Foster, PhD, Wendy Huss, PhD, and Gyorgy Paragh, MD, PhD—this study used a precision-medicine approach, focused ultra-deep DNA sequencing, to systematically compare clonal mutations between sun-exposed and non-sun-exposed skin areas.
“We show that targeted ultra-deep sequencing of skin DNA samples is a tool that can effectively identify potentially cancer-causing cumulative skin damage before the appearance of visible skin changes,” says Dr. Paragh, a dermatologist, Interim Co-Chair of the Department of Dermatology and Assistant Professor of Oncology at Roswell Park and co-senior author on the new study. “Our work shows that sun exposure in the skin leads to specific patterns of UV-induced mutations. We also showed that the burden of mutations could be determined from clinically relevant small skin samples and that this information can be combined in a clinically meaningful way to compare individual skin mutation levels.”
The researchers outline a bioinformatics pipeline for accurately characterizing these low-frequency mutations.
“Our work not only confirms the existence of microscopic groups of cells in the normal skin with DNA alterations, but also allowed us to discover the systematic differences between the mutations caused by UV from the ones caused by aging or other environmental factors,” reports the paper’s co-first and co-corresponding author, Dr. Wei, who is an Associate Professor of Oncology from the Department of Biostatistics and Bioinformatics, and the Co-Director of Bioinformatics Core Resource at Roswell Park. “The UV-induced mutations often occur in specific sites or ‘hotspots’ of human genes, and, interestingly, some of these sites are rarely mutated in non-sun-exposed skin even with aging or other factors.”
The team uncovered several other patterns regarding UV-induced mutations. They report that these mutations tend to result in changes of genes that modify protein function and are associated with specific contexts of DNA sequence, and that the clones harboring the mutations are generally larger in sun-exposed skin areas than the ones in non-sun-exposed areas.
The investigators note that many of their findings were unexpected. They report, for example, a high quantity of low-frequency background mutations in both sun-exposed and non-sun-exposed areas. And while the existence of mutational hotspots has already been established, this study revealed that over one-third of the differences between the mutations in sun-exposed and non-sun exposed areas were due to mutations in just six codons.
Another novel finding was the existence of mutation-exempt” genomic regions in non-sun-exposed skin. These genomic areas, which are never mutated in detectable clones during skin aging, can lose their mutation-exempt status when exposed to sun. Further exploration is required to fully understand the mechanisms behind this observation.
“Based on this work, we are pursuing further studies that will use mutation detection to enumerate skin cancer risk decades before cancers emerge,” says Dr. Paragh. “We intend to use these preliminary results to comprehensively improve skin cancer prevention by better identifying at-risk individuals, improve early treatment strategies and develop better tools for evaluating the efficacy of sun-protection techniques.”
For Upper Facial Lines, DaxibotulinumtoxinA Succeeds in Phase 2
Topline efficacy and safety results from the phase 2 multicenter, open-label study of Revance’s investigational drug candidate daxibotulinumtoxinA for Injection for the combined treatment of upper facial lines, show high levels of patient satisfaction.
The 36-week study enrolled 48 subjects to receive a single treatment of daxibotulinumtoxinA for Injection. Subjects received 40, 32, and 48 units of daxibotulinumtoxinA for Injection respectively in the glabellar complex, forehead and lateral canthal areas.
The key endpoints for efficacy, reported by Revance, were the proportion of subjects achieving a score of none or mild wrinkle severity at maximum contraction (maximum frown, eyebrow elevation, and smile effort) at week 4, as assessed on the Investigator Global Assessment Frown Wrinkle Severity (IGA-FWS), Investigator Global Assessment Forehead Wrinkle Severity (IGA-FHWS), and Investigator Global Assessment Lateral Canthal Wrinkle Severity (IGA-LCWS), respectively.
The study measured duration of effect in responders (those who achieved a score of none or mild at Week 4) as the median time to return to baseline wrinkle severity and time to loss of none or mild wrinkle severity. Both measures were based on investigator and subject assessments. Median time to return to baseline was 33 weeks for glabellar lines and 35 weeks for forehead and lateral canthal lines. Median time to loss of none or mild wrinkle severity was 25 weeks for glabellar lines, 24 weeks for forehead lines, and 28 weeks for lateral canthal lines.
DaxibotulinumtoxinA for Injection was generally safe and well tolerated when all three facial areas were injected simultaneously. There were no treatment-related serious adverse events (SAEs). The most common adverse events (AEs) were injection site erythema (6.3 percent), facial discomfort (4.2 percent) and headache (2.1 percent). No eyelid or brow ptosis was reported.
Using a 7-point Subject Global Satisfaction with Treatment Questionnaire, at week 4, 100 percent of participants reported being at least “Somewhat Satisfied” with the treatment in all three areas, and 83.0 percent, 78.7 percent, and 80.9 percent reported being “Very Satisfied” with the treatment of their glabellar lines, forehead lines, and crow’s feet, respectively.
Revance is currently awaiting a decision on the approval of DaxibotulinumtoxinA for Injection for the treatment of glabellar lines by the FDA, pending a manufacturing site inspection, which was delayed due to COVID-19 travel restrictions.
CLOSE UP with Nehal N. Mehta, MD, MSCE
Is the presence of metabolic syndrome the smoking gun that places psoriasis patients at higher risk for heart attack and stroke?
Maybe, according to new research published in the Journal of the American Academy of Dermatology. “Metabolic syndrome (MetSyn) may identify those patients at highest risk for heart attack and stroke. These data demonstrate that the presence of the MetSyn increased early rupture prone plaque compared to patients with psoriasis without MetSyn,” says study author Nehal N. Mehta, MD, MSCE, a preventive cardiologist and head of the National Heart, Lung and Blood Institute’s Lab of Inflammation and Cardiometabolic Diseases in Bethesda, MD.
Dr. Mehta discussed the implications of this study with Practical Dermatology® magazine.
Why is this topic important to study?
Nehal N. Mehta, MD: MetSyn accelerates heart disease and death. Those with psoriasis were previously shown to have higher rates of MetSyn, and here, we show that when MetSyn is present, there is higher subclinical rupture prone heart disease present.
Describe the research and your findings.
Dr. Mehta: This was a study of 260 participants, and 80 had MetSyn (31 percent). The MetSyn group had a higher burden of cardiometabolic disease, systemic inflammation, non-calcified coronary burden (NCB), and high-risk plaque. After adjusting for all other MetSyn factors, blood pressure and waist circumference remained significantly associated with NCB.
For more details on the new study, see page 25 for additional coverage.
What is the next step?
Dr. Mehta: Efforts to increase MetSyn awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk. Providers, patients and payors need to be aware of this association. We need to increase our efforts to screen for these factors that make up the MetSyn (Dr. Mehta’s 3 B’s: BMI, blood pressure, and blood measures for glucose and cholesterol).
Aerolase Introduces Skin of Color Forum
Aerolase Corp. is launching a Skin of Color Forum (SOCF).
“This Forum is much needed and transformative. It’s been rewarding to work alongside Aerolase to shape its leadership in advancing skin of color dermatology,” says Nashville dermatologist Michael Gold, MD, Chairman of Aerolase’s Medical Advisory Board and member of the SOCF Council, in a news release. “The Forum will spread understanding of how Aerolase achieves optimal outcomes in a wide range of skin of color conditions including hyperpigmentation, melasma, PFB, acne, psoriasis, onychomycosis, rosacea, and other skin concerns.”
“With skin of color patients, medical and aesthetic skin conditions clearly have been treated with limited success and with traditional light-based therapy there are significant risks,” adds Wendy Roberts, MD, a dermatologist in Rancho Mirage, CAand SOCF Council member. “In Aerolase technology we have finally found a go-to device to safely and effectively treat skin of color patients with repeatable results,” says Dr. Roberts.
“Aerolase looks forward to improving patients’ quality of life and practitioners’ efficiency through the SOC Forum initiative. Aerolase stands 100% behind the SOCF mission, and our continuing excellence in skin of color is mission-critical for Aerolase,” says Pavel Efremkin PhD, Chairman and CEO of Aerolase.
More Headlines from DermWire
Revlon Names Martine Williamson As Chief Marketing Officer
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Colleen Goggins Joins ZO Skin Health’s Board Of Directors
This follows the recent acquisition of a majority stake in the business in October by funds managed by Blackstone Tactical Opportunities. As a partner and counsellor to a large variety of businesses and leaders around the world particularly within the consumer goods and healthcare realms, Ms. Goggins brings to the board an abundance of experience with strategically and profitably growing businesses and improving operating results.
SkinCeuticals Taps Stephanie Kramer as GM
Ms. Kramer was Global Senior Vice President of Marketing, Product Innovation and Retail at SkinCeuticals. Prior to joining SkinCeuticals in 2019, Ms. Kramer served as VP of Global Marketing for Kiehl’s Since 1851 also at L’Oréal, where she created its global sustainability program, Made Better. She succeeds Christina Fair, who was promoted last month to President, Active Cosmetics Division, North America.
LEO Pharma Names Jörg Möller as EVP, Global Research and Development
A medical doctor and PhD by training, Mr. Möller’s experience spans multiple therapeutic areas including dermatology and immunology and a variety of technology platforms like biologics and cell & gene therapies. He has a solid track record of working with external partners.
Soliton Appoints Sean J. Shapiro as VP of Sales
“We are very excited to have Sean join our team during this pivotal time for the company as we anticipate clearance of our 510(k) application for cellulite reduction during the first quarter of 2021,” says Brad Hauser, Soliton’s President and CEO. “Sean is a seasoned sales executive who has successfully launched several aesthetic devices in the industry, and we look forward to leveraging his extensive experience as we prepare for the commercial launch of our RAP technology during the first half of next year.”
Katie Cheng Is Cynosure’s New CMO
“Katie’s proven track record of consumer and professional marketing strategy and execution is one of the many reasons we are eager to have Katie join our team,” says Cynosure CEO Todd Tillemans. “Her global experience in transforming businesses, accelerating category growth, and pioneering new platform innovations will help Cynosure and our customers expand our market, gain market share, and delight consumers.”
