Tim Smith joined the MJH Life Sciences team as an assistant editor for HCPLive in August 2022. He graduated from UC Berkeley with a degree in political science, working in multimedia journalism as a staff writer prior to joining MJH. In his spare time, he enjoys reading, watching TV, listening to podcasts, and rock climbing. You can contact him at 

Tim Smith

This installment of the Month in Review series features a set of highlights of the 

 editorial team’s dermatology news coverage. A wide variety of developments in the field of dermatology are covered in this review, including 

Some of the most significant events taking place in November in dermatology included a new approval of bimekizumab, several accepted resubmissions to the FDA, and several stories related to 

Here, the editorial team present this series of major developments from November in the field of dermatology:

FDA Approves Bimekizumab for Adults with Hidradenitis Suppurativa

UCB made an announcement that FDA officials had given their approval to bimekizumab-bkzx (Bimzelx), a humanized IgG1 monoclonal antibody, for the treatment of adults with moderate-to-severe HS. The therapy option is the first and only treatment specifically design with the goal of targeting and inhibiting both interleukin (IL)-17A and IL-17F cytokines.

“The approval of (bimekizumab) in moderate-to-severe hidradenitis suppurativa is welcome given the substantial unmet clinical needs and limited number of treatment options available today,” Alexa B. Kimball, MD, MPH, investigator and professor of dermatology at Harvard Medical School, said in a statement. “In the Phase 3 clinical studies, patients treated with bimekizumab-bkzx achieved deep and sustained clinical responses up to 48 weeks.”

FDA Accepts Resubmitted sBLA for Dupilumab Treatment of Chronic Spontaneous Urticaria

In another FDA-related announcement, Regeneron Pharmaceuticals, Inc. and Sanofi expressed that their resubmitted supplemental Biologics License Application (sBLA) for dupilumab (Dupixent) had been accepted by FDA officials for chronic spontaneous urticaria (CSU) treatment among adults and adolescents aged 12 and older with CSU that has been inadequately managed using H1 antihistamines.

The sBLA’s resubmission was supported by findings resulting from the LIBERTY-CUPID phase 3 clinical program. This program included 3 studies that evaluated the use of dupilumab in individuals with CSU.

FDA Accepts Resubmission of Pz-cel Gene Therapy BLA for Epidermolysis Bullosa

Abeona Therapeutics Inc. also announced in November that that their Biologics License Application (BLA) was resubmitted for the investigational gene therapy known as prademagene zamikeracel (pz-cel), a therapy designed for patients with recessive dystrophic epidermolysis bullosa (RDEB).

The FDA, as part of the process of reviewing this treatment, assigned pz-cel a target action date under the Prescription Drug User Fee Act (PDUFA) for April 29, 2025. Abeona’s resubmission of the treatment’s BLA resulted from recent clinical findings that highlighted the safety and efficacy of pz-cel following a single administration for both the pivotal phase 3 VIITAL study as well as a phase 1/2a study.

Link Identified Between Obesity, Inflammatory Skin Diseases Such as Psoriasis

In another story covered in November, a new study suggested that 1 of the highest associations between obesity and inflammatory skin conditions was the diagnosis of rosacea. However, these data also indicated that morbid obesity had the strongest link with plaque psoriasis and lichen simplex chronicus.

“Obesity as a risk factor has been predominantly associated with psoriasis and hidradenitis suppurativa in cutaneous pathology, but limited studies have explored the connection to other diseases within the inflammatory skin domain,” the investigators wrote.

Positive Phase 3 Results Announced for JNJ-2113 Treatment of Psoriasis

Another story covered in November was the announcement by Protagonist Therapeutics, Inc. that, positive findings from their collaboration with Johnson & Johnson on the ICONIC-LEAD and ICONIC-TOTAL studies in phase 3 research were identified for individuals with psoriasis treated with the oral peptide JNJ-2113 (icotrokinra).

“These positive Phase 3 results confirm the compelling efficacy and safety trends that were observed with the previous Phase 2b FRONTIER-1 and -2 studies, highlighting (JNJ-2113’s) potential as a best-in-class oral agent providing an ideal combination of significant skin clearance with demonstrated tolerability in a once-daily pill for treating plaque psoriasis,” Dinesh V. Patel, PhD, president and CEO of Protagonist, said in a statement.

Study Finds Chronic Psychological Stress Triggers Skin Aging

In another study covered in November, investigators found that chronic psychological stress significantly affects skin homeostasis and can lead to the aging of one’s skin. The research team noted that while data exists regarding biological markers of psychological stress and their effect on immune function and inflammatory markers, their had been very little data on precise causes of visible skin aging’s connection to stress.

“The present investigations confirm that chronic (psychological stress) impacts skin appearance through stress hormones such as cortisol and epinephrine, and these studies have provided the first supporting elements,” the investigators wrote. "Further research and clinical studies need to be conducted to confirm these findings.”

Study Highlights Factors Associated with Diagnostic Wandering Among Patients with HS

Another study highlighted from November showed that diagnostic wandering among individuals with HS is associated with several factors such as being female, being over the age of 40, having an income below minimum wage, and having a lower level of educational attainment. ‘Diagnostic wandering’ refers to the process in which multiple tests, consultations, or referrals are provided to patients without a definitive diagnosis.

“This term often describes situations where healthcare providers are unable to pinpoint the exact cause of a patient's symptoms, leading to a prolonged search for a diagnosis,” the investigators wrote. “This study aimed to assess diagnostic wandering in HS patients and identify associated factors in France.”

Articles

November's dermatology news highlights significant FDA advancements, including the approval of bimekizumab for hidradenitis suppurativa and resubmissions for dupilumab and pz-cel gene therapy. Notable psoriasis developments include the link between obesity and inflammatory skin diseases and positive phase 3 results for JNJ-2113. Additionally, studies reveal chronic psychological stress's impact on skin aging and factors contributing to diagnostic wandering in hidradenitis suppurativa patients. These findings underscore the ongoing progress and challenges in dermatology, emphasizing the need for continued research and innovation.

The November Month in Review features a set of dermatology news coverage highlights, including FDA news and developments in psoriasis.

Dermatology Month in Review | November 2024

Johnson & Johnson announced their submission of 2 supplemental Biologics License Applications (sBLAs) to the 

 for the approval of guselkumab (Tremfya) treatment of children aged 6 and older with moderate-to-severe 

 and those aged 5 and older with active juvenile psoriatic arthritis (jPsA).

Plaque psoriasis is an inflammatory disorder characterized by inflamed, scaly, and often painful or itchy patches on the skin. Juvenile psoriatic arthritis is a subtype of juvenile idiopathic arthritis which is characterized by swelling, chronic inflammation of patients’ joints, and psoriasis. It also is known to frequently manifest first with skin symptoms prior to joint issues.

“This milestone underscores our commitment to transform the standard of care for patients of all ages and builds on our expertise and legacy in IL-23 and immune-mediated diseases,” Liza O’Dowd, MD, vice president and immunodermatology disease area leader at Johnson & Johnson Innovative Medicine, said in a statement. “There is a critical gap in the treatment of children and adolescents with these skin and joint conditions, where debilitating symptoms can present challenges related to physical appearance and ability to function.”

Guselkumab is a monoclonal antibody which is the first therapy option approved specifically for the purposes of targeting the p19 subunit of interleukin (IL)-23. IL-23 is known to be a key contributor to immune-mediated diseases such as iPsA and psoriasis, and guselkumab was formulated to impact the interaction between IL-23 and its receptor.

 in 2017 for the treatment of adult patients with moderate-to-severe plaque psoriasis who are also candidates for either systemic therapy or phototherapy.

 This prior approval had been based on results from the phase 3 VOYAGE 1, VOYAGE 2, and NAVIGATE trials.

The latest FDA submission for pediatric psoriasis results from findings from the phase 3 PROTOSTAR study findings on children with moderate-to-severe disease as well as pharmacokinetic (PK) findings from the phase 3 VOYAGE 1 and 2 studies on adults. The jPsA-related submission draws on PK extrapolation analyses from the DISCOVER 1 and 2 studies on PsA and findings from PROTOSTAR.

PROTOSTAR was a randomized, multicenter, placebo- and active comparator-controlled analysis designed to assess the effectiveness, safety, and pharmacokinetics of guselkumab administered subcutaneously for those aged 6 years and older with psoriasis.

The trials’ co-primary endpoints were Investigator’s Global Assessment (IGA) 0/1 and PASI 75 by Week 16. The VOYAGE 1 and 2 trials were randomized, double-blind, placebo- and active comparator-controlled analyses which assessed both the effectiveness and safety of guselkumab versus placebo and versus adalimumab in adults with psoriasis.

The investigators’ co-primary endpoints were the proportions of individuals given guselkumab versus placebo achieving IGA 0/1 and PASI 90 at the 16-week mark.

The DISCOVER-1 and 2 analyses were multicenter, randomized, double-blinded studies assessing subcutaneous guselkumab injection in patients with active PsA, with DISCOVER-1 including individuals given previous treatment with 1 to 2 tumor necrosis factor inhibitors (TNFi).

In terms of primary endpoints, DISCOVER-1 investigators looked at responses of ACR20 at Week 24. DISCOVER-2 looked at guselkumab’s treatment of biologic-naïve individuals with active PsA, and their primary endpoint was determined to be a response of ACR20 at Week 24.

Johnson & Johnson seeks U.S. FDA approval for first pediatric indications for TREMFYA® (guselkumab). Johnson & Johnson. December 2, 2024. https://www.jnj.com/media-center/press-releases/johnson-johnson-seeks-u-s-fda-approval-for-first-pediatric-indications-for-tremfya-guselkumab. Date accessed: December 2, 2024.

Inman S. FDA Approves Guselkumab for Plaque Psoriasis. HCPLive. July 17, 2024. https://www.hcplive.com/view/fda-approves-guselkumab-for-plaque-psoriasis. Date accessed: December 2, 2024.

Johnson & Johnson has submitted two supplemental Biologics License Applications to the FDA for guselkumab, targeting children with moderate-to-severe psoriasis and juvenile psoriatic arthritis. Guselkumab, a monoclonal antibody, specifically targets the p19 subunit of interleukin-23, a key player in immune-mediated diseases. The applications are supported by data from several phase 3 trials, including PROTOSTAR, VOYAGE 1, VOYAGE 2, and DISCOVER 1 and 2. These trials demonstrated guselkumab's efficacy and safety in both pediatric and adult populations, addressing a critical treatment gap for young patients with these conditions.

Two supplemental Biologics License Applications for guselkumab were submitted to the FDA for treatment of children with plaque psoriasis and active juvenile psoriatic arthritis.

FDA Receives sBLA for Guselkumab Treatment of Psoriasis, Juvenile PsA in Adolescents

Biopharmaceutical company Minghui Pharmaceutical announced that topline results from its new phase 3 study on tofacitinib etocomil (MH004) ointment 1.0% suggest that the drug may be effective for patients aged 12 years and older with 

Prior research has suggested that 2.6% of the global population is impacted by atopic dermatitis, with a total of 204 million people. Among these patients, it has been suggested that 101 million are adults and 103 million are children.

“Atopic dermatitis is a chronic inflammatory condition, particularly prevalent in children, underscoring the urgent need for effective, fast-acting topical therapies beyond corticosteroids.” Jianzhong Zhang, MD, lead investigator and professor of Peking University People’s Hospital, said in a statement. “While corticosteroids are reasonably effective, their long-term use is often limited due to local side effects and safety concerns.”

Tofacitinib etocomil ointment is a topical therapy for those with the inflammatory condition containing a Janus Kinase (JAK) inhibitor designed and formulated with Minghui’s proprietary technologies. The ointment is expected to have improved skin permeability to achieve extensive target inhibition in local skin tissues without systemic toxicities that have been reported for oral JAK inhibitors.

The twice-per-day pan-JAK inhibitor was assessed by Zhang and colleagues during the aforementioned randomized, double-blind, vehicle-controlled phase 3 trial. Multiple centers were used to evaluate the safety profile and efficacy of tofacitinib etocomil 1.0%, with 377 participants being enrolled and randomized in a 2:1 ratio to either the active ointment or a vehicle placebo.

The administration of the drug occurred twice each day for a total of 8 weeks. After the conclusion of this initial treatment period, the study’s subjects began a 44-week open-label extension phase for the purposes of assessing the medication’s long-term safety results.

In terms of primary objectives, the research team’s aims included identifying the proportion of subjects achieving an Investigator Global Assessment (IGA) score of “clear” or “almost clear,” a 75% improvement in the Eczema Area and Severity Index (EASI-75) and at least a two-grade IGA improvement by the 4-week mark (IGA-TS) by this same time point.

The investigators reported that at the 4-week mark, 58.2% of the participants treated with the ointment successfully reached EASI-75, as opposed to the 19.8% who were in the vehicle arm (

 < .0001). In terms of the team’s secondary endpoints, which included as IGA-TS and EASI-75 at the 8-week mark and a ≥ 4-point improvement in Itch Numerical Rating Scale (NRS4), statistically significant results were also reported favoring tofacitinib over placebo.

The investigators highlighted that the ointment was well-tolerated and that its safety profile aligned with the data resulting from earlier phase 2 research. In terms of treatment-related adverse events, such events were noted by the research team as mild to moderate.

They concluded that there were no severe drug-related adverse events during the analysis that were reported. These findings were noted by the Mingui announcement as underscoring the potential of tofacitinib etocomil 1.0% as a safe and efficacious option for individuals who have mild-to-moderate atopic dermatitis.

“[Tofacitinib etocomil] demonstrated superior clinical efficacy in this pivotal phase Ⅲ study, achieving the co-primary endpoints of IGA-TS and EASI-75,” Zhang said in his statement. “The treatment also exhibited a favorable safety profile, and as the leading PI of this study, I am highly encouraged by these results and optimistic about [tofacitinib etocomil’s] potential to advance [atopic dermatitis] care.”

Minghui Pharmaceutical Announces Positive Topline Results from Phase Ⅲ Trial of MH004 (Tofacitinib Etocomil) Ointment in Mild to Moderate Atopic Dermatitis. December 2, 2024. https://www.biospace.com/press-releases/minghui-pharmaceutical-announces-positive-topline-results-from-phase-%E2%85%B2-trial-of-mh004-tofacitinib-etocomil-ointment-in-mild-to-moderate-atopic-dermatitis. Date accessed: December 2, 2024.

A study about how many people around the world have atopic dermatitis, British Journal of Dermatology, Volume 190, Issue 1, January 2024, Page e6, https://doi.org/10.1093/bjd/ljad462.

Minghui Pharmaceutical's phase 3 study on tofacitinib etocomil ointment 1.0% shows promise for treating mild-to-moderate atopic dermatitis in patients aged 12 and older. The study involved 377 participants and demonstrated significant efficacy, with 58.2% achieving EASI-75 at 4 weeks compared to 19.8% in the placebo group. The ointment, a topical JAK inhibitor, was well-tolerated with mild to moderate adverse events. These findings suggest tofacitinib etocomil as a safe and effective alternative to corticosteroids for atopic dermatitis management.

These topline findings regarding MH004, or tofacitinib etocomil ointment 1.0%, demonstrated efficacy for this twice-daily pan-Jak inhibitor in adolescents and adults with eczema.

New Phase 3 Data Suggest Twice-Daily Tofacitinib Etocomil Effective for Atopic Dermatitis

This portion of the latest Lungcast episode includes a discussion of therapies, triggers, and management of AERD.

How to Manage Aspirin-Exacerbated Respiratory Disease

, the topic of Aspirin-Exacerbated Respiratory Disease (AERD) was covered in an interview between host Albert Rizzo, MD, chief medical officer of the American Lung Association (ALA), Mitchell Grayson, MD, an allergist and immunologist from Nationwide Children’s Hospital, and patient advocates Rhonda and Wayne Nelson.

The episode featured a discussion of AERD, its characterization, treatment, and impacts on patients. In this segment of the episode, the 3 guests spoke with Rizzo about the management of the condition and therapies which may be useful.

“When we're talking about what is driving the disease, it tends to be more of the leukotrienes, which are associated with the [type 2 inflammation] model,” Grayson explained. “When we talk about therapy, actually treating for t2 diseases will work, so it fits within that context. But the actual mechanism of why you have the sensitivity to the [cyclooxygenase-1] inhibitors and stuff like that does not fit with a true t1 or t2-high, t2-low kind of model. I think that's kind of the difference [with asthma].”

AERD, also referred to as Samter’s triad, is a collection of chronic inflammatory conditions. The disorder, which affects the lungs and sinuses, is usually initiated with nasal symptoms or rhinitis and then frequently develops into more severe asthma and may require surgery. Grayson was asked by Rizzo about ways of addressing this condition as well as resources for patients with AERD.

“Asthma in general can be exacerbated by many environmental exposures, pollution, strong scents, and things like that,” Grayson noted. “So to try and understand what all those triggers are is an important piece of discussing care with your provider, in terms of what's available out there for people…The American Lung Association has a wonderful website with all kinds of information about clean air as well as the impact on asthma. Other sites that you can go to as well. There's [also] several federal government sites. The EPA has good information on it. The National Heart Lung Blood Institute has a website as well that has good information about these environmental exposures.”

Over the course of this segment of the episode, information on the experiences patients have had in managing AERD were highlighted. Rhonda Nelson spoke on what her experiences had been in managing the condition as well as her own journey with treatment.

Lungcast is a monthly respiratory news podcast series hosted by Albert Rizzo, MD, chief medical officer of the ALA, and produced by 

Videos

Aspirin-Exacerbated Respiratory Disease (AERD), also known as Samter’s triad, is a chronic inflammatory condition affecting the lungs and sinuses, often starting with nasal symptoms and progressing to severe asthma. The latest Lungcast episode featured a discussion on AERD's characterization, management, and treatment options, emphasizing the role of leukotrienes and type 2 inflammation. The episode also highlighted the importance of identifying environmental triggers and provided resources for patients, including information from the American Lung Association and federal agencies like the EPA and National Heart Lung Blood Institute.