Tim Smith joined the MJH Life Sciences team in 2022 and is currently an associate editor for 

. He is also the executive producer of two podcasts: 

. Previously, he was the producer of the Lungcast podcast. He graduated from UC Berkeley and worked in multimedia journalism as a staff writer prior to joining MJH. You can contact him at tsmith@mjhlifesciences.com.

Upadacitinib (15 mg and 30 mg) met the primary end point of SALT score ≤20 at week 24 in both UP-AA1 and UP-AA2 (P<.001 vs placebo)

The 30-mg dose achieved SALT score ≤20 in 55.0% (UP-AA1) and 54.3% (UP-AA2) of patients, versus 1.5% and 3.4% with placebo

Complete scalp hair regrowth (SALT score 0) was reached by up to 22.5% of upadacitinib-treated patients, a stringent secondary end point

Safety through week 24 was consistent with upadacitinib's other approved indications; no new safety signals were identified

The trials included 118 adolescents (age 12-17 years), broadening the evidence base beyond currently available adolescent options

Two phase 3 replicate randomized clinical trials, UP-AA1 and UP-AA2, found upadacitinib (Rinvoq) significantly outperformed placebo in achieving a Severity of Alopecia Tool (SALT) score of 20 or less at Week 24 in adults and adolescents with severe 

, meeting the primary efficacy end point at both the 15-mg and 30-mg doses.¹

Currently only baricitinib, ritlecitinib, and deuruxolitinib are approved oral JAK inhibitors for severe alopecia areata, and only ritlecitinib carries an adolescent indication, leaving a gap for additional systemic options.¹ Prior trials of these agents left many patients short of the SALT ≤20 threshold, with response rates topping out around 35% across treatment groups.² 

UP-AA1 and UP-AA2 enrolled 1399 patients across 25 and 28 countries, respectively, including 118 adolescents ages 12 to 17 years, making the program one of the largest phase 3 evaluations of a JAK inhibitor in this population.¹

Upadacitinib Efficacy in UP-AA1 and UP-AA2

UP-AA1 and UP-AA2 are global, randomized, double-blind, placebo-controlled phase 3 trials conducted at 112 centers in 25 countries and 125 centers in 28 countries, respectively, from October 2023 to July 2025.¹ Eligible patients were adolescents (age 12-17 years, weight ≥30 kg) or adults (age 18 to <64 years) with a SALT score of 50 or greater and no spontaneous scalp regrowth in the prior 6 months.¹ Patients were randomized 2:2:1 to once-daily 15-mg upadacitinib, 30-mg upadacitinib, or placebo for a 24-week double-blind period, followed by a 28-week blinded extension.¹

Baseline mean SALT score across both trials was 83.9 (SD, 18.9), reflecting a population with extensive scalp hair loss.¹ Both trials met the primary end point: SALT score ≤20 at Week 24 was attained by 45.2% (122/270) of patients on 15-mg upadacitinib and 55.0% (149/271) on 30-mg upadacitinib in UP-AA1, compared with 1.5% (2/135) on placebo (

<.001 for both doses).¹ In UP-AA2, response rates were 44.6% (129/289) with 15 mg and 54.3% (157/289) with 30 mg, versus 3.4% (5/145) with placebo (

Separation from placebo emerged as early as Week 8 for both doses in both trials.¹

Upadacitinib Secondary Endpoints and Safety Profile

Both doses also outperformed placebo on more stringent efficacy measures. Complete scalp hair regrowth, defined as SALT score of 0, was reached by 20.3% of patients on 30-mg upadacitinib in UP-AA1 and 22.5% in UP-AA2, compared with 0% and 0.7% on placebo, respectively (

<.001).¹ Clinician-reported outcomes for eyebrow and eyelash hair loss improved significantly with both doses versus placebo across both trials (

Patients on upadacitinib also reported significantly greater improvement in AA-specific quality-of-life measures, including the Alopecia Areata Symptom Impact Scale and Skindex-16 alopecia areata emotions and functioning domains, at Week 24.¹

Treatment-emergent adverse events (TEAEs) were numerically higher with 30-mg upadacitinib than with 15 mg or placebo, occurring in 67.1%, 62.7%, and 57.1% of patients, respectively, in the pooled safety analysis.¹ The most common TEAEs reported in more than 5% of patients in any group were upper respiratory tract infection, acne, elevated blood creatine phosphokinase, and nasopharyngitis.¹ Serious adverse events occurred in 2.3% of patients on 30-mg upadacitinib, 1.6% on 15 mg, and 0.4% on placebo, with no deaths reported in either trial.¹

Investigators characterized the safety profile as consistent with upadacitinib's other approved indications, with no new safety signals identified.¹

Upadacitinib is already approved for multiple inflammatory indications, including atopic dermatitis, a condition frequently comorbid with alopecia areata.¹ A third study is underway to evaluate long-term efficacy, safety, and dose adjustment strategies through Week 52 of UP-AA1 and UP-AA2, which will help define upadacitinib's place relative to baricitinib, ritlecitinib, and deuruxolitinib in severe alopecia areata.¹

Mostaghimi A, Gooderham MJ, Lynde C, et al. Upadacitinib for severe alopecia areata in adults and adolescents: two phase 3 UP-AA randomized clinical trials. JAMA Dermatol. Published online August 12, 2026. 

King B, Ohyama M, Kwon O, et al; BRAVE-AA Investigators. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(18):1687-1699. doi:10.1056/NEJMoa2110343.

Articles

Two large, global phase 3 trials evaluated upadacitinib in adolescents and adults with severe alopecia areata (baseline mean SALT ~84). Both 15 mg and 30 mg once daily achieved robust Week 24 scalp regrowth, with early separation from placebo by Week 8 and meaningful gains across complete regrowth, brows/lashes, and patient-reported quality of life. TEAEs were dose-related and aligned with the known upadacitinib profile; serious events were uncommon and no deaths occurred. Ongoing follow-up will inform durability and positioning versus other oral JAK inhibitors.

In the UP-AA trials, both upadacitinib doses outperformed placebo on SALT score ≤20 at week 24 in adults and adolescents with severe alopecia areata.

Alopecia

News

news page, resources on the topics of disease- and specialty-specific medical news and expert insight can be found. Content includes articles, interviews, videos, podcasts, and breaking news on health care research, treatment, and drug development.

Clinical

clinical page is a resource for content on every specialty, disease, and topic available on our medical news site.

UP-AA: Upadacitinib Attains Primary Endpoint in New Alopecia Areata Data

Diana Isaacs, PharmD, is an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic.

Switching patients from daily basal insulin to once-weekly insulin icodec (Awiqli) requires a distinct dosing calculation clinicians have not previously had to apply, given the agent's extended half-life and slower time to steady state. Getting the conversion right matters for glycemic stability during the transition period.

Converting Basal Insulin Patients to Insulin Icodec

, hosts Diana Isaacs, PharmD, and Natalie Bellini, DNP, walked through the practical mechanics of switching patients from existing basal insulin regimens to icodec, the first once-weekly basal insulin approved for type 2 diabetes.

Watch the full episode discussing the commercial availability of Awiqli

The conversion begins with the patient's current total daily basal dose. Rather than simply multiplying by 7 to approximate a weekly equivalent, the initial dose calls for roughly 50% more, reached by multiplying the daily dose by 10.5, because the longer half-life delays time to steady state and a higher starting dose helps patients reach it faster. A patient taking 10 units of daily basal insulin would calculate to approximately 105 units, rounded to the nearest available increment of 100 or 110 units, before returning to a maintenance dose of 7 times the original daily amount, or 70 units weekly, for subsequent doses.

Titration will also depart from familiar basal insulin algorithms. Rather than adjusting every 3-4 days, once-weekly dosing limits adjustment frequency to ≤once per week, with clinicians reviewing 2-4 weeks of fasting and premeal glucose data before making changes, typically in 10% to 20% increments.

Hospital admission poses a separate practical question the hosts addressed directly. Because the average inpatient stay runs <3 days, well short of the weekly dosing interval, clinicians may often leave the icodec regimen untouched during a hospitalization and manage glucose with correction-dose insulin as needed, checking the timing of the patient's last dose. Isaacs and Bellini suggested inpatient glycemic control could ultimately prove more stable under a properly dosed weekly basal regimen, since it is not intended to cover meals or drive overnight drops the way rapid-acting or poorly matched basal doses can.

Patient education needs will differ by starting point. Insulin-naive patients are unlikely to be affected by the larger unit numbers involved, while patients transitioning from daily doses of 10 to 20 units to weekly doses of 70 units or more will need more deliberate counseling to avoid confusion or dosing errors.

Collectively, the hosts framed once-weekly dosing as a meaningful reduction in treatment burden, particularly for patients with caregiver support needs or a history of suboptimal adherence to daily injections, with anticipated gains in patient satisfaction expected to outweigh the learning curve required of both patients and prescribers.

Editors’ Note: Isaacs reports disclosures with Dexcom, Abbott, Lilly, Novo Nordisk, Medtronic, Insulet, and others. Bellini reports disclosures with Abbott Diabetes Care, MannKind, Povention Bio, and others.

Novo Nordisk. Novo Nordisk's Awiqli, the first once-weekly basal insulin for adults with type 2 diabetes, now available in the US. 

. August 11, 2026. Accessed August 12, 2026. 

https://www.prnewswire.com/news-releases/novo-nordisks-awiqli-the-first-once-weekly-basal-insulin-for-adults-with-type-2-diabetes-now-available-in-the-us-302847645.html

Videos

In this segment from the latest episode of Diabetes Dialogue, Diana Isaacs, PharmD, and Natalie Bellini, DNP, discuss switching patients from basal insulin to Awiqli.

Endocrinology

The HCPLive endocrinology page is a comprehensive resource for clinical news and insights on endocrine system conditions. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for diabetes, hormonal disease, and more.

This page also hosts content previously published by EndocrinologyNetwork. 


Type 1 Diabetes

Saakshi Khattri, MD, is a board certified Dermatologist, Rheumatologist and Internist and one of only a handful of triple board-certified physicians across the US.

Saakshi Khattri, MD, outlines her key practice-changing takeaways for dermatologists and rheumatologists.

Practice-Changing Perspectives on IL-23 Inhibition and Early Intervention in Psoriatic Disease

In the final segment, Saakshi Khattri, MD, synthesizes practice-changing messages from the risankizumab data across psoriasis and PsA for both dermatologists and rheumatologists.

For dermatologists, she underscores that while no prospective prevention trials have definitively established that any biologic class prevents PsA, retrospective claims and database analyses indicate a class-level signal that IL-23 inhibition may be associated with reduced PsA incidence in patients with psoriasis. On this basis, she considers IL-23 inhibitors, including risankizumab, to be strong systemic options for psoriasis patients, particularly those at elevated risk for joint disease.

From the rheumatology perspective, Khattri points to the 5-year data demonstrating radiographic non-progression and sustained clinical efficacy with risankizumab in PsA as especially important. She notes that the combination of structural protection, durable clinical response, and the agent’s relatively infrequent dosing schedule aligns with key concerns voiced by patients, who often ask about both how long a drug will work and how many injections per year are required. The absence of newly emerging long-term safety concerns further supports its role as a long-term treatment option in appropriate candidates.

Khattri also introduces the concept of a “window of opportunity” in psoriatic disease, drawing an analogy to established paradigms in rheumatoid arthritis. She suggests that earlier initiation of systemic therapy—potentially with IL-23 inhibition, given current data—may offer a chance to influence the trajectory of disease and possibly reduce the likelihood of progression from psoriasis to PsA, even though this remains a hypothesis rather than a proven principle. She concludes by reiterating that, taken together, the data on potential PsA risk reduction, durable radiographic outcomes, and stable long-term safety make IL-23 inhibition, and risankizumab specifically, a valuable component of the therapeutic armamentarium for psoriatic disease.

Video Series

 suggest germline genetic variants may help explain why CAR T cell therapy outcomes vary so widely between patients.

Investigators performed whole genome sequencing on patients with aggressive lymphoma treated with axicabtagene ciloleucel in the ZUMA-1 and ZUMA-7 clinical trials, in partnership with Kite Pharma.

Analysis focused initially on genes associated with hemophagocytic lymphohistiocytosis (HLH), a rare hyperinflammatory syndrome with biochemical similarities to cytokine release syndrome (CRS), the most common toxicity of CAR T cell therapy.

Investigators found that variants in STXBP2 were enriched among patients with high-grade toxicity in the ZUMA-1 cohort, a finding supported by in vitro experiments showing that STXBP2-deficient CAR T cells had impaired degranulation and increased inflammatory cytokine production.

Extending the analysis genome-wide, variants in ADAMTSL3 were linked to protection from toxicity, while variants in PTPN22 were strongly associated with greater CAR T cell expansion, across both ZUMA-1 and ZUMA-7.

HCPLive spoke with Mark B. Leick, MD, a medical oncologist and physician scientist at Massachusetts General Hospital who led the study, about its design and what the findings could mean for CAR T cell manufacturing and patient management going forward.

Q&A: Germline Variants May Predict CAR T Cell Toxicity, With Mark Leick, MD

HCPLive: What motivated you and your colleagues to investigate whether inherited germline genetics could influence outcomes after CAR T cell therapy?

Leick: CAR T cells are different from every other form of therapy that came before. It's not like a Bayer aspirin, where every dose is chemically identical. CAR T cells are manufactured from a patient's own T cells, so they carry all of that patient's ancestral genetic polymorphisms and mutations. Because of this, how CAR T cells behave varies from patient to patient in ways we can't totally understand.

Going into this study, we had some idea of which patients were at high risk of toxicity. Patients with a large tumor burden, or higher baseline levels of inflammation, tend to be more likely to have serious side effects. But beyond that, we didn't have a good understanding of why some patients go through catastrophic toxicities and others don't. It's a little like COVID-19, where some patients end up on a ventilator with severe immune inflammation and others sail through with minimal side effects.

Our hypothesis was founded on a rare disease called hemophagocytic lymphohistiocytosis (HLH), which classically affects pediatric patients, usually kids under age 5. In that disease, patients are born with defects in how their lymphocytes, T cells, and NK cells kill virally infected cells. When those lymphocytes can't kill effectively, they become continually activated and trigger an inflammatory cascade that can become life-threatening.

In the CAR T cell field, we've long recognized that the biochemical features of HLH and CRS after CAR T cell therapy are very similar, and the toxicity mechanism is thought to be similar as well: in HLH it's an inactivated T cell trying to kill a virally infected target, and in CAR T cells it's a CAR T cell trying to kill a tumor target, but the end result is the same, cytokines are produced that activate the myeloid system and drive high fevers, low blood pressure, and other symptoms.

Since HLH has a genetic basis, and we now know less severe forms of these mutations can present later in life, we hypothesized that some of those less severe variants might be present in patients who develop severe toxicity after CAR T cell therapy.

HCPLive: Can you walk our audience through what you eventually found?

Leick: We partnered with Kite Pharma, the largest producer of CAR T cell products, which gave us access to DNA samples, CAR T cell level measurements, clinical data, and serum biochemical data from patients across the ZUMA-1 and ZUMA-7 clinical trials of axicabtagene ciloleucel in patients with aggressive lymphoma.

We performed whole genome sequencing, but because these early CAR T cell trials only included around 100 patients, we needed a narrow hypothesis rather than an unrestricted genome-wide search. So we focused on fewer than 20 genes associated with HLH.

We defined a combined toxicity endpoint that captured patients with high-grade CRS, high-grade neurologic toxicity, or those who received tocilizumab, the antidote for CRS, since those patients likely would have had higher-grade toxicity without it. Among that pool, we found 6 patients with variants in the gene STXBP2, which is involved in lymphocyte degranulation, compared with none in the control cohort without high-grade toxicity.

We followed up with wet lab studies, comparing CAR T cells from patients with the variant to CAR T cells from controls, and found that cells with STXBP2 variants became more inflamed when they encountered target cells. We also introduced the CAR T cell gene and the specific variants into healthy donor T cells and saw the same result in vitro.

We then sought to replicate this finding in the ZUMA-7 cohort, an independent group of patients treated with the same CAR T cell product, but earlier in their line of therapy and with less inflammation overall. We didn't see the same STXBP2 finding there, which we think reflects that these patients had less severe disease and fewer prior treatments.

With both cohorts available, we could also look beyond toxicity. We found that variants in PTPN22 were strongly correlated with CAR T cell proliferation across both ZUMA-1 and ZUMA-7. PTPN22 helps regulate normal T cell biology and serves as a brake on T cell receptor activation, so there's a plausible mechanism: lose the brake, and T cells become more activated and proliferate more.

In fact, 2 patients had the exact same mutation, and that led them to have the highest CAR T cell expansion of all the 100 patients in ZUMA-1, suggesting that there is some sort of gain of function advantage to having that mutation in the context of CAR T.

HCPLive: Is there anything else you'd like to highlight, including any limitations?

Leick: I'd add a couple of limitations. Germline genetics analysis requires comparing genetic variation within populations of comparable ancestry, and because clinical trial accrual in the United States skews toward patients of European ancestry, our study was limited mostly to that population. We only had a couple of non-European patients, not enough to support any meaningful analysis. We'd love to study this in more diverse populations.

Our study was also focused on one product, axicabtagene ciloleucel, so these findings may not apply to other CAR T cell products or disease types beyond lymphoma. We're working in the lab now to understand whether this applies more broadly.

As for clinical implications, this doesn't mean patients with these variants got severely ill. No one died in either trial, and even knowing a patient had these variants, we likely wouldn't manage them differently since we're already fairly good at treating these toxicities. Where I think this becomes more relevant is in choosing donor T cells for allogeneic CAR T cell products, since a single donor's cells can be used to manufacture products for dozens or hundreds of patients, and in using natural human genetic variation as an alternative to CRISPR-based screens to identify genes, like PTPN22, that could be engineered into future CAR T cell products to improve efficacy.

Editor’s Note: Leick reports relevant disclosures with BioNTech, Cabaletta Bio, and Adaptimmune.

Leick MB, Sun B, Birocchi F, et al. Genomic correlates of clinical CAR T cell activity. 

. 2026;11(121). doi:10.1126/sciimmunol.aef4134

Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544.

Whole-genome sequencing in aggressive lymphoma treated with axicabtagene ciloleucel implicates germline variation as a contributor to interpatient heterogeneity in CAR T efficacy and toxicity. An HLH-informed candidate approach associated STXBP2 variants with severe CRS/neurologic toxicity in ZUMA-1, supported by in vitro evidence of impaired degranulation and heightened cytokine release. Genome-wide analyses identified ADAMTSL3 variants linked to reduced toxicity and PTPN22 variants correlated with greater CAR T expansion across ZUMA-1 and ZUMA-7. Generalizability is constrained by ancestry and product specificity.

New research links germline genetic variants to CAR T cell toxicity risk and expansion in lymphoma patients treated with axi-cel.

Hematology

Germline Variants May Predict CAR T Cell Toxicity, With Mark Leick, MD

Robert Sarkany, MD, FRCP, is a consultant dermatologist at St John's Institute of Dermatology at Guy's and St Thomas' Hospital in London and at the Lister Hospital.

Erythropoietic protoporphyria (EPP) has no approved disease-modifying treatment. The only 

-approved therapy for the condition, afamelanotide, increases pain-free light exposure by boosting skin pigmentation, but it does not address the underlying protoporphyrin IX buildup driving the disease.²

More than 25,000 patients in the US and EU live with EPP or the related X-linked protoporphyria (XLP), and up to 5% progress to acute liver failure requiring transplantation.¹ Investigational agent PORT-77, an oral ABCG2 transporter inhibitor, blocks the efflux of protoporphyrin IX from red blood cells into plasma.

In the phase 2a GATEWAY trial, a placebo-controlled crossover study in 19 adults with EPP, the drug produced mean plasma PPIX reductions of 79% at the higher dose and 63% at the lower dose.¹ These effects appeared within hours of dosing and showed no rebound after treatment stopped.¹ No serious adverse events or treatment discontinuations occurred, and the data were presented at the European Hematology Association 2026 Congress in Stockholm.¹

If confirmed in the planned phase 2b/3 PATHWAY trial, these reductions could translate into fewer phototoxic episodes and meaningful gains in quality of life. Robert Sarkany, MD, FRCP, is a consultant dermatologist and senior photodermatology consultant at St John's Institute of Dermatology, Guy's and St Thomas' Hospital, London. He has treated and researched EPP for more than 3 decades. In the following Q&A interview with 

, Sarkany discusses the significance of the phase 2a data:

: What was your initial reaction to the phase 2a PORT-77 data showing rapid reductions in plasma PPIX in patients with EPP?

: They're exciting findings, there's no question about it, and this is an exciting time in EPP. I've been involved with patients and research into EPP for over half of my life, since the early 1990s. I'd say this is a very exciting period of drug development in EPP, and PORT-77 is a very exciting part of that.

: Why is reducing plasma PPIX considered such an important therapeutic target, and how could this translate into clinical benefit?

Patients with EPP have one of two different genes that cause it, but it's the same underlying problem: a defect in the production of heme. The biosynthetic pathway of heme is disrupted either at the beginning or at the end, and the result is an accumulation of one of the intermediates, called protoporphyrin. This accumulates in patients who have a deficiency of ferrochelatase, or a dominantly inherited increased-activity mutation in ALAS2, another enzyme in the pathway. The end result is high levels of protoporphyrin in erythroblasts, reticulocytes, and red blood cells in the red cell series, because that's where 80% of heme is made, since most heme is used for hemoglobin.

Protoporphyrin has two types of toxicity in the body. One is that it's chemically toxic when there's light, essentially blue or violet light, producing various free radical activated oxygen species. That matters in the skin because protoporphyrin is in blood vessels not far below the surface, a millimeter or two down, and those blood vessels, carrying red cells full of protoporphyrin, may be vulnerable to endothelial damage. That causes bouts of severe pain when there's endothelial necrosis from the phototoxicity. The other toxicity is in the liver: protoporphyrin is excreted into the bile because it's hydrophobic, so the concentrations in the liver are quite high, and despite there being no light there, through a different mechanism, the high concentrations are toxic to liver cells, particularly bile canalicular cells.

What this means is that 100% of patients with EPP suffer from severe bouts of 3- to 4-day-long burning pain, severe enough to prevent sleep and unresponsive to conventional analgesia, mainly on the hands and face, and that's lifelong for everybody. About 3% of patients also develop progressive cirrhotic liver disease, fibrosis, and bile canalicular damage, eventually presenting with liver failure and cholestasis that usually requires liver transplantation.

What PORT-77 does is prevent the protoporphyrin that has accumulated within the red cell series from leaving the red cell and leaking into plasma. Until this work, I thought it was just passive diffusion out of red cells into the plasma, but it turns out there's a specific transporter involved, called ABCG2. Its old name is the breast cancer resistance protein; it's an ATP-binding cassette transporter that pumps xenobiotics and various biochemicals and vitamins out of cells in the body. It was found to be involved in breast cancer cells pumping out cytotoxics, but it also functions in red blood cells and erythroblasts or reticulocytes, pumping protoporphyrin out from the red cell into the plasma.

If you can keep the plasma protoporphyrin concentration lower, that matters because it's the plasma that's in contact with vascular endothelium in epidermal blood vessels in the skin, where the damage causing severe photosensitivity occurs, and it's also the plasma in contact with bile canalicular cells and hepatocytes. So the theory is, if you can keep the concentration in the plasma down, whatever it's doing in the red blood cell, you may be able to protect against the skin and liver toxicity. It looks as though that's the case.

: Given the favorable safety profile and rapid PPIX reductions, what are your biggest reasons for optimism, and what questions remain unanswered?

The biggest reasons for optimism are that with the higher dose used in this trial, about 19 or 20 patients with EPP were dosed with placebo and then with drug at different doses, a higher dose and a lower dose, without knowing the order. There was single blinding in terms of whether they were on placebo during that period, a couple of weeks, maybe 10 days or so, and during that period they didn't know whether they were on placebo or active drug. The endpoint was a fairly objective one: plasma protoporphyrin concentration.

In the people on the higher dose, the minimum fell within about 6 hours, and within 4 days there was a full decrease: the lowest fall was 57%, the average was 79%, and the highest was virtually no plasma protoporphyrin at all, something like 98% or 99%. These are quite big falls, there were no patients without a significant fall, and the effect appeared dose dependent, which is a positive thing.

That's the data we've got from patients, along with a much bigger group of phase 1 healthy volunteers showing minimal, if any, side effects. What reassures me is that blocking the ABCG2 transporter isn't something one would predict to be very toxic. One could argue there might be completely unrelated side effects, but about 1 in 2,000 people in Japan have a homozygous knockout mutation in ABCG2, and they're well, aside from a slightly increased uric acid concentration in their plasma; I don't think there are any other known ill effects. ABCG2-null mice also seem fine, and ABCG2-null mice that also have EPP seem fine as well. In fact, they're much better off than mice with the transporter protein still working, and their survival is longer, because their liver seems to do better.

So from the phase 1 and phase 2a data, it's looking pretty safe, and it's looking promising in terms of plasma levels; the mouse work suggests it will have clinical implications, and theory would support that. What we now need is the full trials, to see not only whether we can decrease plasma protoporphyrin in these patients, but whether we indeed end up with significantly less photosensitivity, as we would expect.

As PORT-77 moves into the phase 2b/3 trial, what outcomes and endpoints will you be watching most closely?

 Ideally, you look at liver as well as skin. Skin photosensitivity is the big endpoint, since it's part of the disease in almost everybody who has it. You would hope not only to replicate these very significant and fast reductions in plasma levels of protoporphyrin in patients in the phase 2b/phase 3 trial, but you'd also want to measure how many phototoxic episodes, how many painful episodes of photosensitivity lasting 3 or 4 days, happen during [UNCLEAR — please review] compared to normal. Are there changes in well-being data and quality of life data, that sort of thing, and as many clinical correlates as we can use for reductions in photosensitivity?

You can also get a general idea as to whether anything is happening with the liver, but the problem is one can't really trial for that specifically, which would be interesting and nice, because it's a rare complication that happens in a small number of people, at one point in their lives, developing over a few years. So that's not going to be trialable, because most patients aren't having that complication. So the clinical outcomes that matter most are about pain on sun exposure.

Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.

GondolaBio. GondolaBio announces positive phase 2a results demonstrating 79% plasma protoporphyrin IX reduction and disease-modifying potential of PORT-77 for erythropoietic protoporphyria. Published June 22, 2026. Accessed August 12, 2026. 

https://gondolabio.com/gondolabio-announces-positive-phase-2a-results-demonstrating-79-plasma-protoporphyrin-ix-reduction-and-disease-modifying-potential-of-port-77-for-erythropoietic-protoporphyria/

HCPLive. FDA approves afamelanotide to treat erythropoietic protoporphyria. Published October 2019. Accessed August 12, 2026. 

https://www.hcplive.com/view/fda-afamelanotide-erythropoietic-protoporphyria

Erythropoietic protoporphyria and X-linked protoporphyria lack disease-modifying therapy, with afamelanotide limited to photoprotection via pigmentation. PORT-77, an oral ABCG2 inhibitor, aims to reduce toxicity by preventing protoporphyrin IX efflux from erythroid cells into plasma. In a 19-patient phase 2a placebo-controlled crossover study, plasma PPIX fell rapidly and dose-dependently (mean 79% high dose; 63% low dose), without rebound, serious adverse events, or discontinuations. Translational rationale links lower plasma PPIX to reduced endothelial phototoxicity and potentially hepatobiliary injury.

Recent phase 2a findings on PORT-77 show rapid, dose-dependent plasma PPIX reductions in erythropoietic protoporphyria and X-linked protoporphyria.

Dermatology

The HCPLive dermatology page is a resource for medical news and expert insights on skin disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for dermatologic conditions, and more.

Q&A: PORT-77 Phase 2a Results in Adults with EPP and XLP

Mark Metersky, MD, and Ashwin Basavaraj, MD, discuss novel therapy brensocatib on the 1-year anniversary of its FDA approval.

Pulmonology

Infectious Disease condition center page is a comprehensive resource for clinical news and insights on respiratory health. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for asthma, COPD, interstitial lung disease, COVID-19, and more.

One Year Later: How Brensocatib Has Changed Bronchiectasis Care

Rima Rachid, MD, from Boston Children’s Hospital.

Rima Rachid, MD, explains how bile acid metabolism and Bacteroides colonization drive durable Treg cell induction after FMT for peanut allergy.

Allergy

Allergy condition center page is a comprehensive resource for clinical news and insights on allergic and inflammatory diseases. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for food and seasonal allergies, as well as allergic asthma and related conditions.

Food Allergy

Fecal Transplant Sustains Peanut Allergy Protection to 12 Months

Abigail Brooks is a strategic content lead overseeing 

She joined MJH Life Sciences in August 2023 shortly after graduating from Monmouth University where she earned her BA in Communication with a concentration in Public Relations/Journalism and later an MA in Interactive Digital Media. She enjoys traveling, running, and reading books. She can be reached at abrooks@mjhlifesciences.com.

Experts discussed FCS diagnostic scoring tools, diagnostic delays, and new data on olezarsen and plozasiran for lowering triglycerides in a recent clinical forum.

Cardiology

Cardiology condition center page is a comprehensive resource for clinical news and insights on cardiovascular and cardiometabolic diseases. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for heart disease and cardiovascular events, as well as associated diabetes, renal failure, and more...

Dyslipidemia

FCS Diagnosis and Management Explained: Clinical Forum Insights

In this segment from the latest episode of Diabetes Dialogue, Diana Isaacs, PharmD, and Natalie Bellini, DNP, discuss the commercial release of insulin icodec.

Type 2 Diabetes

Insulin Icodec Dosing Strategies for Type 2 Diabetes

In this segment from the latest episode of Diabetes Dialogue, Diana Isaacs, PharmD, and Natalie Bellini, DNP, discuss the promise of continuous ketone monitoring in T1D.

Continuous Ketone Monitoring May Guide SGLT2i Use in T1D

Arvid Harder, PhD candidate of Karolinska Institutet, Stockholm, Sweden.

New genome-wide data show AERS+ and AERS− subtypes of major depressive disorder diverge in heritability and metabolic genetic correlations.

Psychiatry

Psychiatry condition center page is a comprehensive resource for clinical news and insights on mental illnesses. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for depression, schizophrenia, bipolar disorder, anxiety, and more.

Major Depressive Disorder

Major Depressive Disorder condition center page, resources on the topics of medical news and expert insight into depression can be found. Content includes articles, interviews, videos, podcasts, and breaking news on MDD research, treatment, and drug development.

Metabolic Traits Differentiate AERS+, AERS− MDD Subtypes, With Arvid Harder

In this discussion, Eichenfield discusses which advances in eczema he sees as most impactful and where unmet needs remain for pediatric patients.

Atopic Dermatitis

Atopic Dermatitis condition center page, audiences can find a variety of coverage mediums for medical news and updates, including articles, video interviews, podcasts, and breaking news on dermatitis research, treatment, and drug development.

Q&A: Where the Pediatric Atopic Dermatitis Systemic Pipeline Stands

Victoria Johnson joined MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and is now an assistant managing editor for HCPLive and RheumatologyLive. She doesn’t have enough time for her numerous hobbies. You can reach her at vjohnson@mjhlifesciences.com.

The bispecific TSLP/IL-13 inhibitor BEL512 met its primary endpoint and all secondary endpoints in adults with chronic rhinosinusitis with nasal polyps.

BEL512 Improves CRSwNP and Symptoms in Phase 2 trial

Chelsie Derman is an associate editor for 

who covers allergy and  psychiatry. She joined MJH Life Sciences in September 2023 after graduating from The College of New Jersey with a bachelor’s degree in journalism and professional writing. In her free time, she enjoys creative writing and reading.

DT120 ODT produced a 5.4-point placebo-adjusted HAM-A reduction at week 12 in the phase 3 Voyage trial for generalized anxiety disorder.

Voyage: DT120 ODT Reduces Anxiety in Phase 3 GAD Trial

Brad Rovin, MD, discusses persistent gaps in IgA nephropathy diagnosis and treatment, from RAS inhibition limits to the promise of B-cell-targeted therapies.

IgA Nephropathy

The HCPLive Berger disease page is a resource for medical news and expert insights on IgA nephropathy. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments in Berger disease, and more.

Nephrology

The HCPLive nephrology page is a resource for medical news and expert insights on kidney disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments in nephrology, and more.

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