Stelara Approved for PsO in Kids Ages 6-11
Stelara (ustekinumab, Janssen) is now approved for pediatric patients (6-11 years of age) with moderate to severe plaque psoriasis (PsO). Stelara targets both interleukin (IL)-12 and IL-23 and is administered as an injection given under the skin, dosed four times per year after two starter doses.
The FDA approval for pediatric use is based on results from the CADMUS Junior study. In the open-label, single-arm, multicenter Phase 3 clinical trial of 44 patients with moderate to severe plaque psoriasis, 77 percent of patients achieved clear or almost clear skin at week 12 after two doses. Secondary endpoints included the proportion of patients achieving 75 percent or 90 percent improvement in their Psoriasis Area and Severity Index (PASI) score at week 12 compared to baseline. Study results showed 84 percent and 64 percent of patients achieved a PASI 75 response and PASI 90 response, respectively.
The safety profile observed in CADMUS Junior was similar to the safety profile from studies in adults with plaque psoriasis.
Genentech’s Tecentriq plus Cotellic and Zelboraf Approved for Advanced Melanoma
Tecentriq (atezolizumab) is now approved in combination with Cotellic (cobimetinib) and Zelboraf (vemurafenib) for the treatment of BRAF V600 mutation-positive advanced melanoma patients. The safety profile observed in the Tecentriq combination was consistent with the known safety profiles of the individual medicines, according to manufacturer Genentech, a member of the Roche Group.
The approval is based on results from the Phase 3 IMspire150 study, in which the addition of Tecentriq to Cotellic and Zelboraf helped people live longer without their disease worsening or death (progression-free survival, PFS), compared to placebo plus Cotellic and Zelboraf (median PFS 15.1 months versus 10.6 months respectively.
FDA Fast Tracks Leo Pharma’s Delgocitinib Cream for Hand Eczema
Delgocitinib cream, Leo Pharma’s investigational topical pan-Janus kinase (JAK)-inhibitor, has been granted Fast Track designation by the FDA for the potential treatment of adults with moderate to severe chronic hand eczema (CHE).
Delgocitinib inhibits activation of the JAK-STAT pathway. The cream formulation of delgocitinib is not currently approved by any regulatory authorities.
Revance to Launch RHA Collection of Fillers
Revance Therapeutics, Inc. will introduce the RHA Collection of dermal fillers, Resilient Hyaluronic Acid, and the HintMD financial technology platform, in the US this month.
The RHA Collection of dermal fillers is designed with a crosslinking method that preserves the hyaluronic acid network to more closely mimic natural HA found in the skin.
Revance has recently concluded the RHA Collection PrevU early clinical experience education and training program for select practices ahead of the consumer launch of the RHA Collection and plans to share observations in the near future. The same commercial infrastructure is anticipated to roll out DaxibotulinumtoxinA for Injection for the treatment of glabellar lines upon FDA approval later this year.
Positive Phase 3 Results for Dermavant’s Tapinarof Cream for Psoriasis
Dermavant Sciences shared positive results from PSOARING 1 and PSOARING 2, two identical, multi-center, randomized, vehicle-controlled, double-blind, parallel studies to evaluate the efficacy and safety of tapinarof cream 1% in adult patients with plaque psoriasis.
In both PSOARING 1 (N=510) and PSOARING 2 (N=515), tapinarof cream demonstrated highly statistically significant improvement in Physician Global Assessment (PGA) score of clear (0) or almost clear (1) with a minimum 2-grade improvement compared to vehicle from baseline at Week 12 (both P<0.0001), thus meeting the primary endpoint of each trial. Additionally, in both trials, tapinarof cream demonstrated highly statistically significant improvement in PASI75 from baseline at Week 12 (both P<0.0001), a key secondary endpoint. In addition, up to 80 percent of patients achieved a ≥1-grade improvement in PGA across both studies.
New Data Supports the Safety and Efficacy of Dupixent in Adults and Children with AD
Two new studies reinforce the efficacy and safety of Dupixent for atopic dermatitis in children and adults.
In the Phase 3 LIBERTY AD pediatric trial data, nearly three times as many children achieved clear or almost clear skin when treated with Dupixent and topical steroids, and more than two-thirds experienced at least a 75 percent overall improvement of their disease compared to topical steroids alone at 16 weeks. More than three times as many children experienced a significant reduction in itch with Dupixent compared to topical steroids alone, and improvements in itch and disease severity were observed with Dupixent as early as two weeks after the first dose and continued throughout active treatment.
The results, which appear in the Journal of the American Academy of Dermatology, also show that Dupixent significantly improved outcomes and quality of life, with no new safety signals.
Results from the LIBERTY AD adult open-label extension three-year trial extend the available data on the safety and sustained efficacy of Dupixent in adults with moderate-to-severe AD for up to 3 years, supporting its long-term continuous use with no lab monitoring needed. These results appear in American Journal of Clinical Dermatology.
Acne Ally: Bringing Care to Patients
When COVID-19 restrictions went into place this spring, dermatologists Dennis Porto, MD and Farhaad Riyaz, MD realized patients may not have access to physicians or be comfortable visiting practices. Concerned that acne patients may turn to Internet sources for acne information or care—many non-specific or unreliable—they decided to bring care to patients on the Internet. They founded AcneAlly.com, an online service that provides patients access to a board certified dermatologist and a standardized approach to assessment and long-term monitoring of acne. The service uses a blend of store-and-forward and synchronous telemedicine for patient assessment.
“It really gets to the heart of the relationship between the physician and the patient and allows them the full spectrum of care, including isotretinoin,” Dr. Porto says. “None of these other online services have dermatologists, and they don’t offer isotretinoin, which is oftentimes what patients need if they have severe acne. This was a way that we could meet the needs of this very vulnerable population, while steering them towards dermatologists who are best equipped to treat their condition.”
“Historically a dermatologist ends up seeing a patient 10 years after they’ve had bad acne and now they just have horrific scarring that they’re coming to get help with,” Dr. Riyaz says. “We’re hoping to eradicate that. We never want to see acne patients who didn’t have access and now they have horrible scarring. We want to solve that problem.”
Drs. Riyaz and Porto say people from all socioeconomic statuses are signing up. “It really comes down to access,” Dr. Farhaad says. “Some people are not insured for example, but they just have this one medical problem, they have severe acne.” The service seems to be expanding access to patients who wouldn’t otherwise see a dermatologist, rather than taking patients from dermatology practices, they say.
If a prescription is appropriate, the patient will receive it. It can be filled through partnered pharmacies or a pharmacy of the patient’s choice.
Inspire(d) Insights with Practical Dermatology®
Your Patients Are Talking About… Diet and Psoriasis Symptoms
To help readers better understand the issues that patients with skin diseases face, Practical Dermatology® partnered with Inspire to provide Inspire(d) insights. With more than 100 national patient organization partnerships and over two million members, Inspire is a vital social network that enables safe sharing of health experiences and social support.
“Dealing with gut issues is working,” says one Inspire psoriasis community member. For many Inspire members, diet is important to their treatment. Testing diet strategies and cutting out foods that can potentially cause inflammation like gluten, dairy, and nightshades are part of discussions on Inspire’s psoriasis support forum. Specifically, 8.2 percent of psoriasis Inspire members are actively searching for fasting options as a part of their treatment process. However, some express skepticism about their diet’s relationship with psoriasis symptoms.
Practical Dermatology Clinical Focus-Psoriasis editor Jennifer Soung, MD, a dermatologist at Southern California Dermatology in Santa Ana, CA, the director of clinical research at Southern California Dermatology in Santa Ana, CA, and clinical professor at Harbor–UCLA, says that her psoriasis patients often ask about diet.
“Diet can lessen the severity of psoriasis, not cure it,” she cautions. “Dietary changes are meant to accompany medical treatments to lessen disease severity/symptoms and possible comorbidities.”
Dr. Soung urges her patients to keep a food journal to identify any dietary triggers and consider consulting with a dietician. Still, there are some one-size-fits-all tenets of a good diet. “Low-glycemic index foods cause slower and smaller rises in blood sugar,” she says. “Eat whole fruits, not fruit juices and whole grains, not processed grains.” She also encourages psoriasis patients to get regular exercise, eat fish for its anti-inflammatory properties, and use avocado, peanut, and olive oil for dressing and sautés. “Spice it up,” she adds. “Turmeric can fight inflammation in psoriasis and psoriatic arthritis.”
Galderma Launches New Rosacea Awareness Campaign
Galderma is partnering with rosacea patient and celebrity stylist Brad Goreski for the national awareness campaign, Face Up to Rosacea, to encourage people frustrated with this chronic skin condition to take action by consulting with a dermatologist.
Face Up to Rosacea offers rosacea patients information to help them navigate their treatment journey, including skincare tips, treatment information, lifestyle hacks, dermatologist advice and stories from other people living with rosacea.
CLOSE UP with Christopher Bunick, MD, PhD
Antibiotics are used extensively and often for long periods of time in the treatment of acne. They are highly effective, but concerns of antimicrobial resistance have tempered their usage. A better understanding of how specific antibiotics work can help guide acne treatment decisions. It is under this guise that Christopher Bunick, MD, PhD, an Assistant Professor of Dermatology at Yale School of Medicine in New Haven, CT, and colleagues took a closer look at the chemical structure of sarecycline (Seysara, Almirall). They found this novel tetracycline-derived oral antibiotic does have a different mechanism of action than others in its class and this may be why C. acnes strains display a low propensity for the development of resistance to this drug. Their study appears in the Proceedings of the National Academy of Science. Here, Dr. Bunick discusses the findings and their implications.
Why is this Topic Important to Study?
Dr. Bunick: Acne vulgaris is one of the most common skin conditions in the world, and oral antibiotics are one of the most prescribed therapies for inflammatory acne. It is essential to know how medications like sarecycline work and how the mechanisms of action differ among the acne therapies available to patients. Detailed knowledge of the molecular functions of sarecycline and other antibiotics help a physician choose the proper medicine for a patient and be good stewards of antibiotic use in an era where concerns about antibiotic resistance exist. It also helps inform the patient why they are being given a certain treatment.
Describe the Research and Your Findings.
Dr. Bunick: Our research team determined an atomic resolution structure using x-ray crystallography of sarecycline bound to the bacterial ribosome. Ribosomes are the cellular machinery that translate messenger RNA into proteins in the cell. Our work provided a three-dimensional picture of how sarecycline functions at its target site on the ribosome to inhibit bacterial protein synthesis, which we believe is the major way medications like sarecycline treat acne. We found sarecycline was a potent inhibitor of the initiation of protein synthesis and due to its unique molecular structure at the “C7 position,” sarecycline made contacts with the messenger RNA in the ribosome. Contacts with messenger RNA had not been previously observed among the tetracycline class of antibiotics. These findings suggest that sarecycline has unique aspects to its mechanism of action that could account for several of its defining properties such as narrow-spectrum activity and low propensity for development of antimicrobial resistance. In fact, our structure showed that the special C7 position on sarecycline interfered with bacterial drug resistance mechanisms. This has direct relevance to its use in the clinic for acne therapy.
What is the Next Step?
Dr.Bunick: It is important that we learn more about how the unique structural features of sarecycline and its interaction with the ribosome impact what is going on inside bacteria. Our research team will use a technique called ribosomal profiling to examine how the entire bacterial genome is affected by sarecycline. This will provide even clearer insight into how sarecycline works. We are very thankful to have support from Dr. Ayman Grada, MD and the entire Almirall team to be able to pursue this research.
