Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic AhR modulating agent (TAMA)

Tapinarof, a novel, first-in-class small-molecule topical therapeutic aryl hydrocarbon receptor (AhR) modulating agent (TAMA), is in clinical development for the treatment of psoriasis and atopic dermatitis. The efficacy of tapinarof in psoriasis is attributed to its specific binding and activation of AhR, a ligand-dependent transcription factor, leading to the downregulation of pro-inflammatory cytokines, including interleukin-17, and regulation of skin barrier protein expression to promote skin barrier normalization. AhR signaling regulates gene expression in immune cells and skin cells, and has critical roles in the regulation of skin homeostasis. Tapinarof-mediated AhR signaling underlies the mechanistic basis for the significant efficacy and acceptable tolerability observed in early phase clinical trials of tapinarof cream in the treatment of psoriasis

Black-Box Immigration Federalism

In Immigration Outside the Law, Hiroshi Motomura confronts the three hardest questions in immigration today: what to do about our undocumented population, who should decide, and by what legal process. Motomura’s treatment is characteristically visionary, analytically rich, and eminently fair to competing views. The book’s intellectual arc begins with its title: “Immigration Outside the Law.” As the narrative unfolds, however, Motomura explains that undocumented immigrants are “Americans in waiting,” with moral and legal claims to societal integration

Black-Box Immigration Federalism

In Immigration Outside the Law, Hiroshi Motomura confronts the three hardest questions in immigration today: what to do about our undocumented population, who should decide, and by what legal process. Motomura’s treatment is characteristically visionary, analytically rich, and eminently fair to competing views. The book’s intellectual arc begins with its title: “Immigration Outside the Law.” As the narrative unfolds, however, Motomura explains that undocumented immigrants are “Americans in waiting,” with moral and legal claims to societal integration

Tapinarof Cream 1% Once Daily for the Treatment of Plaque Psoriasis: Case Photography of Clinical Outcomes from Three Phase 3 Trials

Tapinarof cream 1% (VTAMA(®); Dermavant Sciences, Inc.) is a non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration (FDA) to treat plaque psoriasis in adults and under investigation for the treatment of psoriasis in children down to 2 years of age, and for atopic dermatitis in adults and children down to 2 years of age. The PSOARING phase 3 clinical trial program evaluated tapinarof cream 1% once daily (QD) in adults with mild to severe plaque psoriasis for up to 52 weeks (NCT03956355, NCT03983980, NCT04053387). Here we present case photography documenting outcomes in the PSOARING trials. Cases illustrate various outcomes across different body areas, including responses meeting the formal FDA-mandated regulatory endpoint of a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear) and a decrease of at least 2 points from baseline at week 12, meaningful clinical improvement not meeting this formal endpoint, patient-reported outcomes, and pre-specified adverse events of special interest (AESIs). Tapinarof cream 1% QD demonstrated rapid and highly statistically significant efficacy, with improvements in disease activity and quality of life. In addition, a high rate (40.9%; n = 312/763) of complete disease clearance (PGA = 0) was achieved, and improvements exceeding National Psoriasis Foundation treatment goals were demonstrated. After first achieving complete disease clearance (PGA = 0), patients treated with tapinarof experienced an approximately 4-month remittive effect off therapy. Incidence and severity of folliculitis and contact dermatitis AESIs were generally mild or moderate, localized to the site of application, and associated with low discontinuation rates. Medical images are of importance in trials of dermatologic therapies to inform clinical decision-making and enhance patient assessment. Tapinarof cream 1% QD is efficacious and well tolerated in patients with mild to severe plaque psoriasis, with clinically relevant improvements seen early in the course of treatment. Clinicaltrials.gov numbers: NCT03956355, NCT03983980, NCT04053387

Shrinking the Post-Plenary Power Problem

In this essay, Professor Michael Kagan responds to Professor Matthew J. Lindsay\u27s article, Disaggregating “Immigration Law.” Professor Kagan posits a majority of Supreme Court justices appear to be at least occasionally uneasy with the plenary power doctrine that has shaped immigration law since the Chinese Exclusion Case, but they are not all sure how to live without it either. He argues so long as this remains the case, the Court’s immigration jurisprudence is likely to be incrementally favorable to immigrants on the whole, but tentative, inconsistent, and incoherent in some important ways. He concludes the importance of Professor Lindsay’s intervention is that it helps point a way to find clarity in this transitional period

State Regulation of Federal Contractors: Three Puzzles of Procurement Preemption

This Article unpacks three doctrinal puzzles at the intersection of federalism and federal contracting, using student loan law as its anchoring case study. Currently, more than $1 trillion of federal student loan debt is serviced by private financial institutions under contract with the Department of Education. These loan servicers have allegedly engaged in systemic consumer abuses but are seldom held accountable by the federal government. To bridge the accountability gap, several states have recently passed “Student Borrower Bills of Rights.” These state laws include provisions to regulate the student loan servicing industry, including the Department’s federal contractors. States undoubtedly have legitimate interests to protect their residents, communities, and local economies against industry malfeasance. The overarching question, however, is whether federal law prohibits states from performing this remedial function. This Article offers a fresh look at three doctrinal puzzles at the heart of that debate. The first puzzle is whether the federal government’s constitutional immunity extends to shield federal contractors from generally applicable state laws. The second puzzle is whether federal procurement laws preempt state licensing of federal contractors. The third puzzle is whether federal contracts that expressly incorporate state law can save state law from preemption. Individually and collectively, how these puzzles are resolved may have far-reaching implications—not only for the future of student loan law, but also for federalism and federal contracting more generally