Recent Developments

UCSF Apologizes for Dermatology Experiments on Prisoners in 1960s

The University of California, San Francisco apologized for conducting unethical dermatology experiments on at least 2,600 incarcerated men in the 1960s and 1970s.

Experiments included putting pesticides and herbicides on the men’s skin and injecting the substances into their veins. Incarcerated men who volunteered for the studies were paid $30 a month to participate. Other experiments included placing small cages with mosquitos close to the participants’ arms or directly on their skin to determine host attractiveness of humans to mosquitos.

The new report by The UCSF Program for Historical Reconciliation (PHR) raises ethical concerns over how the research was conducted at the California Medical Facility (CMF) in Vacaville. There was no record of informed consent in many cases. In addition, subjects did not have any of the medical conditions that any of the experiments could have potentially treated or ameliorated, the report states. This research continued until 1977 when the state of California halted all human research in state prisons, a year after the federal government did the same.

The research was performed by Howard Maibach, MD and William Epstein, MD, both faculty in UCSF’s Department of Dermatology. Dr. Epstein died in 2006, and Dr. Maibach remains an active member of the department.

The PHR report was conducted by Aimee Medeiros, PhD, associate professor of humanities and social sciences, and Polina Ilieva, associate university librarian and UCSF archivist, under the guidance of Brian Dolan, PhD, chair of the Department of Humanities and Social Sciences.

The report found that “Maibach practiced questionable research methods. Archival records and published articles have failed to show any protocols that were adopted regarding informed consent and communicating research risks to participants who were incarcerated.”

In a review of publications between 1960 and 1980, the committee found virtually all of Dr. Maibach’s studies lacked documentation of informed consent despite a requirement for formal consent instituted in 1966.

“Based on our archival research of internal human subject research review board(s) records and state of California hearings proceedings, PHR has concluded that Dr. Maibach and others engaged in questionable informed consent practices at the prison, especially before 1969,” the report states.

According to the report, researchers bypassed requirements to report their research to UCSF’s human subjects committee through a nonprofit organization, the Solano Institute for Medical and Psychiatric Research (SIMPR), which coordinated human subjects research at CMF.

Drs. Maibach and Epstein were trained by Albert Kligman, MD, a dermatologist at the University of Pennsylvania who conducted studies at Holmesberg Prison in Philadelphia. In 2019, Penn Medicine stated that, while Kligman’s research might have met the legal standards of its time, it was unethical and disrespectful of its subjects, many of whom were imprisoned Black men. The demographics at CMF at the time of Maibach’s research are not fully known, but there is no indication the research was directed specifically at Black men, the new report states.

Dr. Maibach showed remorse in a letter to colleagues.

“I regret having participated in research that did not comply with contemporary standards,” he wrote. “The work I did with colleagues at CMF was considered by many to be appropriate by the standards of the day, although in retrospect those standards were clearly evolving. I obviously would not work under those circumstances today—as the society in which we live in has unambiguously deemed this inappropriate. Accordingly, I have sincere remorse in relationship to these efforts some decades ago.”

In a letter to his department, Jack Resneck, MD, chair of the UCSF Department of Dermatology, wrote that “much of the research described clearly contradicts our community’s ethical values … . Even if this research may have been accepted by some in its time, it is essential that we now acknowledge the harms that were done and the inconsistency with our UCSF values.”

In conclusion, the committee recommended that UCSF disseminate these findings, educate its community about this history, begin an oral history project with those who were subjected to research at CMF between 1955 and 1977, offer an official statement of remorse, and continue researching UCSF’s past.

“UCSF apologizes for its explicit role in the harm caused to the subjects, their families, and our community by facilitating this research, and acknowledges the institution’s implicit role in perpetuating unethical treatment of vulnerable and underserved populations—regardless of the legal or perceptual standards of the time. Truth-telling and rebuilding trust are foundational to our commitment to reconciliation work and, in that spirit, we must acknowledge the failures in our history in order to identify a path forward that is informed by our PRIDE values and commitment to justice, equity, diversity, and inclusion,” said UCSF Executive Vice Chancellor and Provost Dan Lowenstein in an official statement of remorse for Drs. Maibach’s and Epstein’s research at CMF.

“There’s more work that we need to pursue to understand this and other parts of our history. Reconciling our past provides a way of bringing clarity to the present and the path forward,” added Lowenstein, who steps down from his position as EVCP at the end of this year. “To paraphrase the German poet Goethe: ‘They who cannot draw from 3,000 years are living from hand to mouth.’”

Positive Data for DFD-29 for Rosacea

Journey Medical Corporation shared positive PK comparability data of DFD-29 and key updates on the progress of its pivotal Phase 3 clinical study of DFD-29 for the treatment of papulopustular rosacea in collaboration with Dr. Reddy’s Laboratories Ltd.

The PK study was designed as a single-center, randomized, open-label, single-dose, 3-treatment, crossover, comparative bioavailability study of DFD-29 (Minocycline Modified Release Capsules 40mg) compared to Solodyn (Minocycline Modified Release Tablets 105mg). A total of 24 healthy adult volunteers were enrolled and examined for up to 30 days. The primary objectives of the study were to assess: 1) the comparative bioavailability of DFD-29 with Solodyn following a single oral dose administration under fasting conditions in healthy adult human subjects; and 2) the effect of food on the bioavailability of DFD-29. The secondary objective of the study was to evaluate and compare the safety and tolerability profiles of each study treatment. The study successfully demonstrated that the systemic exposure of DFD-29 (40mg) was significantly lower than that of Solodyn. Additionally, the study showed that food did not have a significant effect on the pharmacokinetics of DFD-29.

“We are pleased to continue advancing the DFD-29 clinical program as part of our collaboration with Dr. Reddy’s. The PK data indicate the safety of DFD-29 is on par with Solodyn. To date, the enrollment of our pivotal, Phase 3 program has reached 96 percent. We look forward to providing further updates on the DFD-29 program including potential topline data from the Phase 3 studies, anticipated in the first half of 2023. Journey Medical also plans to file a New Drug Application in the second half of 2023. We hope to show the potential of DFD-29 as an effective treatment option for the millions of patients worldwide who suffer with rosacea,” says Claude Maraoui, Co-Founder, President and Chief Executive Officer of Journey Medical, in a news release.

FDA Fast Tracks pDNA Vaccine for Skin Cancer

Immunomic Therapeutics received FDA fast track designation for the clinical study of their plasmid DNA vaccine ITI-3000 in patients with Merkel cell carcinoma (MCC), a rare but aggressive form of skin cancer.

Enrollment is in progress for the Phase 1 study that uses the PharmaJet Stratis Needle-free Injection System (NFIS) exclusively. The PharmaJet Stratis NFIS was chosen due to its ability to deliver the vaccine precisely to the intramuscular tissue layer.

“The FDA’s decision to grant FTD underscores the potential for the ITI-3000 program to address a serious unmet need and serve as a meaningful therapeutic option for patients with Merkel cell carcinoma,” says Dr. William Hearl, Chief Executive Officer of ITI. “We are committed to unlocking the full potential of ITI-3000 in patients with this aggressive form of skin cancer. We expect to report top-line data from our ongoing Phase 1 trial of ITI-3000 in MCC patients next year and look forward to working closely with the FDA on a potential next phase clinical study design, while simultaneously continuing dialogue with possible partners.”

Fast Track Designation is designed to facilitate the development and expedite the FDA review of drugs to treat serious conditions and fulfill unmet medical needs, enabling drugs to reach patients earlier.

Promising Topline Results in Phase 3 Trial of Roflumilast in AD

Arcutis Biotherapeutics, Inc.’s roflumilast met the key primary and secondary endpoints in the INTEGUMENT-2 pivotal Phase 3 trial of adults and children aged 6 years and older with mild to moderate atopic dermatitis (AD).

The new findings are consistent with positive topline results from the INTEGUMENT-1 trial released in November 2022, the Company reports.

Roflumilast cream 0.15% is a once-daily, non-steroidal topical phosphodiesterase-4 (PDE4) inhibitor.

The study met its primary endpoint, with 28.9% of individuals treated with roflumilast cream 0.15% achieving IGA Success, defined as a validated Investigator Global Assessment–Atopic Dermatitis (vIGA-AD) score of clear or almost clear plus a 2-grade improvement from baseline at Week 4, compared to 12% of individuals treated with vehicle, the study showed.

Roflumilast cream also demonstrated rapid and statistically significant improvements compared to vehicle on key secondary endpoints, including 42% of individuals treated with roflumilast cream 0.15% achieving a 75% improvement in Eczema Area and Severity Index (EASI-75) at Week 4 compared to 19.7% treated with vehicle.

In an additional secondary endpoint, the study evaluated reduction in itch in individuals 12 years of age and older, with 30.2% of individuals treated with roflumilast cream achieving a 4-point reduction in Worst Itch Numeric Scale (WI-NRS) at Week 4 versus 12.4% for vehicle-treated subjects.

Roflumilast cream 0.15% was well tolerated. The incidence of Treatment Emergent Adverse Events (TEAEs) was low in both active treatment and vehicle arms, with most TEAEs assessed as mild to moderate severity. Overall, the incidence of adverse events was low.

Rocatinlimab Shows Promise in AD

Rocatinlimab—a novel, patient-tailored monoclonal antibody therapy—showed promising results in atopic dermatitis patients both while taking the drug and for up to 20 weeks after the therapy was stopped, Mount Sinai researchers reported in The Lancet.

Rocatinlimab inhibits OX40—an immune molecule involved in activating inflammatory cells that play a key role in the development of atopic dermatitis and other inflammatory diseases.

The results indicate that rocatinlimab has the potential to change the genetic makeup of a person’s atopic dermatitis for the long term and possibly help sustain lasting results without continued use.

In this Phase 2b multicenter, double-blind, placebo-controlled study, 274 patients were recruited and (rocatinlimab: n=217; placebo: n=57) randomly assigned 1:1:1:1:1 to rocatinlimab every 4 weeks (150mg or 600mg) or every 2 weeks (300mg or 600mg) or subcutaneous placebo up to week 18, with an 18-week active-treatment extension and 20-week follow-up. This trial was conducted at 65 sites within the United States, Canada, Japan, and Germany.

Percent change from baseline in the Eczema Area and Severity Index (EASI) score was assessed as the primary endpoint at week 16, and significance versus placebo was achieved with all active rocatinlimab doses (-48% to -61%) compared to placebo (-15%). All active dose cohorts also continued improving after week 16, and most patients maintained the response for at least 20 weeks off treatment.

The results support rocatinlimab as a safe and effective treatment for moderate to severe atopic dermatitis, with potentially long-lasting efficacy and disease modification.

Adverse events reported were generally similar between rocatinlimab groups. Common adverse events during the double-blind period included fever, chills, headache, aphthous ulcers (canker sores), and nausea.

“At week 36, all participants had been on the treatment for at least 18 weeks,” says Emma Guttman, MD, PhD, Waldman Professor and System Chair, The Kimberly and Eric J. Waldman Department of Dermatology; Director, Center of Excellence in Eczema; and Director, Laboratory of Inflammatory Skin Diseases, at the Icahn School of Medicine at Mount Sinai, and senior author of the study. “By this time, we saw that while the drug achieved the primary endpoints in all doses versus the placebo, it’s also a drug that improves over time, which is really unusual and unique among currently available treatment options.”

Researchers plan to continue this investigation in a phase 3 program in 2023. Future studies will also include a larger study population, longer follow-up, and exploration of combination therapy (such as rocatinlimab plus topical corticosteroids).

UCB’s Bimekizumab Performs Well in Studies for HS and Psoriatic Arthritis

UCB’s bimekizumab may be a promising treatment approach in adults with moderate to severe hidradenitis suppurativa, according to topline results from two Phase 3 studies, BE HEARD I and BE HEARD II.

The positive results from these two studies will form the basis of global regulatory license applications for bimekizumab in hidradenitis suppurativa starting in Q3 2023.

Bimekizumab is an investigational product; its efficacy and safety have not been established for any indication in the US, and it is not approved by the FDA.

Across the two studies, bimekizumab met the primary endpoint, demonstrating statistically significant and consistent clinically meaningful improvements over placebo in the proportion of patients who achieved the Hidradenitis Suppurativa Clinical Response (HiSCR50) at week 16. Bimekizumab demonstrated depth of response with statistically significant improvements at week 16 over placebo in the percentage of patients achieving HiSCR75, a key secondary endpoint in both studies. HiSCR50 and HiSCR75 are defined as at least either a 50% or 75% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count. The safety profile of bimekizumab in both studies was consistent with previously reported studies with no new observed safety signals.

“Hidradenitis suppurativa is a chronic, painful and debilitating inflammatory skin disease that impacts patients’ physical, psychological, and social well-being. This reduced quality of life is compounded by the limited treatment options currently available,” says Professor Gregor Jemec, MD, PhD, Chairman, Department of Dermatology Zeeland University, Roskilde, Denmark. “The positive top-line clinical outcomes from BE HEARD I and BE HEARD II are promising and demonstrate the value that bimekizumab can potentially bring to the hidradenitis suppurativa community.”

Two new studies published in The Lancet highlight the efficacy and safety of bimekizumab in the treatment of adults with active psoriatic arthritis who were biologic-naïve and/or tumor necrosis factor inhibitor inadequate responders (TNFi-IR).

The 24-week results from the Phase 3 BE OPTIMAL study and 16-week results from the Phase 3 BE COMPLETE study evaluated the efficacy and safety of bimekizumab in the treatment of adults with active psoriatic arthritis who were biologic-naïve and TNFi-IR, respectively.

A significantly higher proportion of patients treated with bimekizumab achieved improvements in joint symptoms at week 16 compared with placebo—as measured by ACR50, the primary endpoint—with a consistent clinical response observed in both biologic-naïve and TNFi-IR populations. In addition, at week 16, a significantly higher proportion of bimekizumab-treated patients compared with placebo achieved high levels of skin clearance—as measured by PASI 90, a secondary endpoint—with a consistent clinical response in both populations. The safety profile of bimekizumab was consistent with safety data seen in previous studies with no new observed safety signals.

Bimekizumab is a humanized monoclonal IgG1 antibody that is designed to selectively inhibit both interleukin 17A (IL-17A) and interleukin 17F (IL-17F), two key cytokines driving inflammatory processes.

Melanoma Immunotherapy Drugs Working

New research published in JAMA Network Open suggests that the use of new pharmacological therapies is associated with a decrease in the melanoma mortality rate in the US population.

In the population-based cross-sectional study of patients with cutaneous melanoma from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2019, the melanoma mortality rate (MMR) decreased from 2013 to 2017 as a result of the availability of new and effective treatment options after 2011.

After the introduction of newer treatments in 2011 (most after 2013), a significant reduction in MMR was seen from 2013 to 2017 in the US for the first time in the past 40 years, the study showed. Rates increased from 1975 to 1988. No statistically significant change in MMR was seen from 1988 to 2013, but the MMR decreased significantly from 2013 to 2017.

Study: Isolated Nail PsO Not Linked to Metabolic Syndrome Risk

Isolated nail psoriasis does not increase risk for metabolic syndrome, according to a letter to the editor in the Journal of the European Academy of Dermatology & Venereology.

The analysis included 156 patients with a diagnosis code for isolated nail psoriasis and controls. There was no difference between nail psoriasis patients and controls for average body mass index and systolic blood pressure, for either closest to diagnosis or highest value recorded.

The groups had similar rates for metabolic syndrome components, including hypertension, hypertriglyceridemia, low high-density lipoprotein, elevated hemoglobin A1c, or related medical conditions such as hypercholesterolemia, obesity, and type 2 diabetes.

“Isolated NP patients can be counselled that they are not at significantly higher risk for metabolic syndrome, which may help decrease patient anxiety and health care costs associated with additional monitoring,” the study authors conclude.

Close Up with Michael Kaminer, MD

Microneedling is growing in popularity, but researchers aren’t sure exactly how it stimulates regeneration within skin. To answer this question, Michael S. Kaminer, MD, a founding partner at SkinCare Physicians in Chestnut Hill, MA, and colleagues created an ex-vivo tissue model that closely mimics the actual microneedling procedure to elucidate its mechanism of action. They found that microneedling stimulates proliferation and barrier renewal of the skin and increases the levels of inflammatory cytokines and angiogenic growth factors in a dynamic and time-dependent fashion. Here, Dr. Kaminer discusses the study results, which appear in Scientific Reports.

Why is this topic important to study?

Michael S. Kaminer, MD: Microneedling has become a popular treatment for skin rejuvenation with the promise of efficacy with limited recovery periods, however robust data on the true efficacy of microneedling are lacking. Furthermore, efficacy data on the combined use of microneedling with supplemental topical therapies are also lacking. To that end, this study achieves two important goals. First, it creates a truly novel model that enables us to accurately study microneedling with or without adjunctive topical therapies. Second, it begins to give measurable data on microneedling efficacy and mechanisms of action that start to put some science behind the hype that has typically been associated with microneedling.

Describe the research and your findings.

Dr. Kaminer: With Loreal’s research and innovation team, we were able to develop a reproducible ex-vivo tissue model to study the skin response to microneedling. Utilizing this model enabled us to demonstrate that microneedling stimulated cell proliferation, epidermal regeneration, and barrier renewal of the skin as well as increased levels of inflammatory cytokines and angiogenic growth factors. Importantly, this paper is one of the first to utilize microneedled ex-vivo skin to demonstrate its regenerative properties. This will enable the team to utilize this novel research tool to evaluate the efficacy of microneedling alone and in combination with a variety of future active ingredients and therapies and gives us the opportunity to broaden our understanding of tissue remodeling following microneedling. An interesting avenue of future research is to investigate how we might modulate tissue response by utilizing carefully selected active ingredients to combine with microneedling.

What is the next step?

Dr. Kaminer: The next step is to utilize this exciting research model to investigate the effects of microneedling alone and in combination with adjuvant topical therapies. This is a wonderful research tool that will finally enable us to get reliable data and dive deeper into the benefits of microneedling as well as opportunities to enhance microneedling efficacy through the addition of topical therapies.