Victoria Johnson joined the MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and now HCPLive. You can reach her at vjohnson@mjhlifesciences.com

Victoria Johnson

SUMMIT: Bezuclastinib Delivers Durable, Deepening Symptom Relief in NonAdvSM, With Cem Akin, MD

Bezuclastinib, an oral, highly selective type 1 KIT inhibitor, has demonstrated that clinically meaningful symptom improvement not only holds but continues to deepen out to 48 weeks of treatment in patients with nonadvanced systemic mastocytosis (NonAdvSM), with every assessed symptom domain showing progressive gains over the treatment course.

These data were from the pivotal, multicenter, randomized, double-blind, placebo-controlled phase 2 SUMMIT trial and were presented at the 

American Academy of Allergy, Asthma & Immunology (AAAAI)

 2026 Annual Meeting held in Philadelphia, Pennsylvania.

The trial is evaluating bezuclastinib 100 mg once daily versus placebo in patients with NonAdvSM (n = 179; bezuclastinib, n = 119; placebo, n = 60). To discuss the findings and what they mean for a patient population with limited established options, 

 spoke with Cem Akin, MD, Professor of Medicine at the University of Michigan Division of Allergy and Immunology, a leading authority in mast cell disorders and a principal investigator on the trial, during the meeting. Akin also discussed the importance of prioritizing the symptom burden in patients with NonAdvSM, as visualized with SUMMIT trial entry interviews, which were highlighted in the poster he presented at the meeting.

Across the MS2D2 Total Symptom Score, bezuclastinib produced broad, sustained reductions from a mean baseline score of 8.1. At 48 weeks, mean changes from baseline were observed across all symptom domains: itching (–5.2), flushing (–5.1), skin papules (–5.2), fatigue (–6.0), cognitive concentration (–7.3), memory (–5.7), nausea (–5.5), abdominal pain (–3.3), headache (–4.3), bone pain (–4.0), diarrhea (–5.6), brain fog (–3.0), and dizziness (–3.4) — with all symptoms showing deepening improvement from the 24-week timepoint. In total, 86% of bezuclastinib-treated patients achieved a ≥30% reduction in MS2D2 TSS (81/94), and 56.4% achieved ≥50% reduction (53/94) at 48 weeks.

“These interviews were conducted before they were enrolled in the trial, and they focused on different domains, like skin, gastrointestinal, neurocognitive domains and there are some sentences taken directly from the patient interview that kind of tells you the impact of these patients are experiencing. And some of them are really very severe. And I think for somebody who is new to the field, it is absolutely eye opening to recognize what the patient's going through,” Akin said.

On biomarker endpoints, 98.9% of patients (88/89) in the bezuclastinib arm achieved ≥50% reduction in serum tryptase at week 48, compared to 96.1% (49/51) among placebo crossover patients — with median serum tryptase of 4.7 ng/mL (range 1.0–128.0) versus 5.8 ng/mL (range 1.1–143.0), respectively. Patients achieving tryptase below 20 ng/mL reached 91.7% (66/72), and 83.3% (70/84) fell below 11.4 ng/mL. KIT p.D816V variant allele fraction in peripheral blood was reduced to a median of 0.04% (range, 0–10.5) in the bezuclastinib arm versus 0.07% (range 0–12.1) in placebo crossovers, with 98.4% (61/62) of the ITT population achieving ≥50% VAF reduction. The tolerability profile remained favorable through 48 weeks, with serious TEAEs occurring in just 1.7% of bezuclastinib-treated patients and discontinuations due to TEAEs in 9.2% (11/119 in the double-blind period).

Cogent Biosciences submitted a new drug application (NDA) for a broad NonAdvSM indication in December 2025.

Akin’s disclosures include Blueprint Medicines, Cogent, Telios, GSK, and Novartis.

Boggs NA, Rein L, Bose P, et al. Expanded Results From the Phase 2 Summit Trial: Bezuclastinib in Adults With Nonadvanced Systemic Mastocytosis. Presented at: AAAAI 2026 Annual Meeting, February 27-March 2, Philadelphia, Pennsylvania. Abstract #519

Akin C, Boggs NA, Rein L, et al. Results From the Phase 2 Summit Trial of Bezuclastinib in Adults With Nonadvanced Systemic Mastocytosis (NonAdvSM): Patient Experience of Living With NonAdvSM. Presented at: AAAAI 2026 Annual Meeting, February 27-March 2, Philadelphia, Pennsylvania. Abstract #510

Cogent Biosciences announces submission of new drug application for bezuclastinib in nonadvanced systemic mastocytosis. News release. Cogent Biosciences, Inc. December 30, 2025. Accessed January 2, 2025. https://investors.cogentbio.com/news-releases/news-release-details/cogent-biosciences-announces-submission-new-drug-application

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Cogent Biosciences previously submitted an NDA for bezuclastinib at the end of 2025.

Long-Term PIONEER Data Reinforce Avapritinib’s Benefit–Risk Profile in ISM, with Cem Akin, MD

Avapritinib continues to deliver durable symptom control and quality-of-life improvements nearly 4 years into treatment for patients with indolent systemic mastocytosis (ISM), reinforcing its role as a long-term targeted therapy for this chronic disease.

Avapritinib was approved for treating ISM by the United States (US) Food and Drug Administration (FDA) in May 2023.

 Updated data from the Phase 2/3 PIONEER trial (NCT03731260) were presented at the 

 2026 Annual Meeting held in Philadelphia, Pennsylvania, by Cem Akin, MD, Professor of Medicine at the University of Michigan Division of Allergy and Immunology. 

In the updated PIONEER analysis, 226 patients with indolent systemic mastocytosis initiated avapritinib 25 mg once daily across Parts 1, 2, and 3. The median duration of treatment was 46.5 months (range, 0.7–67.2 months).

Long-term efficacy was sustained through approximately 4 years. Among all patients treated with avapritinib, the mean change from baseline in ISM-SAF TSS was −17.66 (SD, 19.32) at Week 48 (n=141) and −17.66 (SD, 19.07) at Week 204 (approximately 4 years; n=85). For the most severe symptom domain (Figure 3), improvement was maintained at 1 year (n=193) and 4 years (n=85).

 at AAAAI, AKin emphasized the importance of the long-term consistency of benefit for ISM, where more than 80% of patients fall into the non-advanced category and historically have relied only on symptomatic therapies such as antihistamines. Prior to avapritinib, available treatments did not meaningfully reduce mast cell burden or target the underlying KIT D816V mutation, which drives over 90% of ISM cases.

Quality-of-life gains were similarly durable: the mean percentage change from baseline in MC-QoL was −30.96% (SD, 37.48) at 1 year and −35.41% (SD, 35.71) at 4 years. In patients who dose-escalated to 50 mg once daily in Part 3 (n=74), median time on 50 mg was 16.5 months (range, 0.2–33.6). These patients had higher baseline KIT D816V VAF and symptom burden; after 24 weeks on 50 mg, 42 of 48 evaluable patients (88%) achieved stable-to-improved ISM-SAF TSS, including 38 with improved TSS, and 42 of 46 (91%) had stable-to-improved MC-QoL, including 38 with improvement.

Safety remained consistent with prior reports. In Part 2, any adverse events occurred in 128 patients (91%) receiving avapritinib 25 mg plus best supportive care versus 66 (93%) with placebo plus best supportive care; grade ≥3 adverse events occurred in 30 (21%) and 15 (21%), respectively. Serious adverse events were reported in 7 (5%) and 8 (11%), and treatment-related adverse events (TRAEs) in 77 (55%) and 32 (45%). In the combined 25 mg cohort across Parts 1–3 (N=226), any adverse events occurred in 224 patients (99%), grade ≥3 events in 108 (48%), serious adverse events in 53 (23%), and serious TRAEs in 3 (1%). TRAEs leading to discontinuation occurred in 6 patients (3%). Among those escalating to 50 mg (n=74), any adverse events occurred in 64 (86%), grade ≥3 events in 13 (18%), serious adverse events in 10 (14%), and grade ≥3 TRAEs in 1 (1%), with no serious TRAEs reported and no treatment discontinuations due to adverse events at the 50 mg dose.

“In the 4 year trial now we are extending those observations, there are some patients who are on the drug for more than 5 years, but on average, 4 year follow up, and the efficacy was sustained at the same level, maybe slightly even improved at 4 years than at 6-month and 1-year time frames,” Akin said.

Akin’s disclosures include Blueprint Medicines, Cogent, Telios, GSK,  and Novartis.

Akin C, Tashi T, Elberink HO, et al. Avapritinib continues to demonstrate durable symptom control with a well-tolerated safety profile: Long-term outcomes from PIONEER. Presented at: AAAAI 2026 Annual Meeting, February 27-March 2, Philadelphia, Pennsylvania. Abstract #509

FDA Approves Avapritinib for the Treatment of Adult Patients with Indolent Systemic Mastocytosis. News release. ACCC. May 24, 2023. 

https://www.accc-cancer.org/view/fda-approves-ayvakit-(avapritinib)-for-the-treatment-of-adult-patients-with-indolent-systemic-mastocytosis-(ism)

Akin discussed how avapritinib continues to demonstrate its benefit in indolent systematic mastocytosis.

AbbVie has announced positive topline results from the phase 3, randomized, placebo-controlled, double-blind AFFIRM study evaluating the efficacy and safety of risankizumab (Skyrizi) subcutaneous (SC) induction treatment versus placebo in adult patients with moderately to severely active Crohn's disease (CD).

As described in the March 2, 2026, press release from the Company, AFFIRM study results showed significantly greater proportions of patients treated with risankizumab SC induction achieved the co-primary endpoints of Crohn's Disease Activity Index (CDAI) clinical remission and endoscopic response at week 12 compared to placebo. Of note, among patients with clinical response after 12 weeks of risankizumab SC induction treatment followed by 12 weeks of maintenance, 67% achieved CDAI clinical remission at week 24 and 57% achieved endoscopic response at week 24.

"Crohn's disease is a complex, often debilitating condition that affects far more than a patient's digestive health, disrupting work, relationships and daily life," Millie Long, MD, MPH, chief of the division of Gastroenterology and Hepatology at University of North Carolina, Chapel Hill, and lead investigator of the AFFIRM study, said in a statement. "These high endoscopic response rates across populations, in particular among those who have not failed an advanced therapy, demonstrate the potential of subcutaneous induction risankizumab as an effective therapy for Crohn's disease."

Risankizumab is an interleukin (IL)-23 inhibitor that selectively blocks IL-23 by binding to its p19 subunit. IL-23, a cytokine involved in inflammatory processes, is thought to be linked to a number of chronic immune-mediated diseases. It is approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of plaque psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis.

The efficacy and safety of risankizumab SC as an induction treatment in adult patients with moderately to severely active Crohn's disease was assessed in the global, phase 3, randomized, placebo-controlled, double-blind AFFIRM study. Co-primary endpoints were percentage of participants with CDAI Clinical Remission (CDAI < 150) and percentage of participants with endoscopic response at week 12.

A total of 289 patients were randomly assigned in a 2:1 ratio to risankizumab SC or placebo. Investigators noted key demographics and baseline characteristics were generally balanced between the risankizumab SC and placebo groups, with 65% having failed advanced therapies for the treatment of CD before. Of those patients, 50% failed ≥ 2 advanced therapies, 23% failed ustekinumab, and 12% failed a Janus kinase inhibitor.

AFFIRM consists of 3 treatment periods, including a placebo-controlled Period A (baseline to week 12) to evaluate the efficacy and safety of risankizumab SC induction treatment, an extended Period B (week 12 to 24) where patients receive blinded or open-label treatments based on their clinical response at week 12, and a 52-week open-label extension Period C where all patients receive the approved risankizumab maintenance treatment.

Results showed significantly greater proportions of patients treated with risankizumab SC induction achieved the co-primary endpoints of CDAI clinical remission (55% vs 30%; 

 <.0001) and endoscopic response (44% vs 14%; 

 <.0001) at week 12 compared to placebo. Among patients with clinical response after 12 weeks of risankizumab SC induction treatment followed by 12 weeks of maintenance, 67% achieved CDAI clinical remission at week 24 and 57% achieved endoscopic response at week 24.

During the 12-week, double-blind, placebo-controlled period, the safety profile of risankizumab SC was consistent with the safety profile observed in Crohn's disease with no new safety risks observed. The most common adverse events observed among patients receiving risankizumab were upper respiratory tract infection, abdominal pain and arthralgia. Serious adverse events occurred in 0.5% of patients in the risankizumab SC group compared to 3.1% in the placebo group.

AbbVie described plans to publish full results in an upcoming medical journal and additionally share them at future medical congresses.

"This study evaluated a difficult-to-treat Crohn's disease patient population, including a majority with a prior failure to advanced therapy, and these data reinforce risankizumab as a leading, effective treatment for patients," said Kori Wallace, MD, PhD, vice president, global head of immunology clinical development at AbbVie. "The level of endoscopic response is a particularly meaningful achievement for Crohn's disease patients; and for AbbVie, these results underscore our continued innovation and research to raise the standard of care."

AbbVie. AbbVie Announces Positive Topline Results from Phase 3 AFFIRM Study Evaluating SKYRIZI® (Risankizumab) Subcutaneous Induction in Patients with Crohn's Disease. March 2, 2026. Accessed March 2, 2026. 

https://news.abbvie.com/2026-03-02-AbbVie-Announces-Positive-Topline-Results-from-Phase-3-AFFIRM-Study-Evaluating-SKYRIZI-R-Risankizumab-Subcutaneous-Induction-in-Patients-with-Crohns-Disease

Brooks A. FDA Approves Risankizumab (Skyrizi) for Ulcerative Colitis. HCPLive. June 18, 2024. Accessed March 2, 2026. 

https://www.hcplive.com/view/fda-approves-risankizumab-skyrizi-for-ulcerative-colitis

Articles

Phase 3 AFFIRM demonstrated that subcutaneous risankizumab induction significantly improved week-12 CDAI clinical remission and endoscopic response versus placebo in moderately to severely active Crohn’s disease. In patients achieving clinical response at week 12 and continuing maintenance, remission and endoscopic response rates at week 24 were 67% and 57%, respectively. The global trial enrolled a largely treatment-refractory population, with 65% having failed prior advanced therapies. Safety was consistent with prior Crohn’s experience, without new signals and fewer serious adverse events than placebo.

Risankizumab achieved superiority for the co-primary and ranked secondary endpoints at week 12 for SC injection versus placebo.

AFFIRM: Risankizumab (Skyrizi) Subcutaneous Induction Achieves Primary Endpoints in Crohn’s Disease

Addressing ICS Hesitancy in Pediatric Asthma Care, With Lynchi Nguyen

Inhaled corticosteroids (ICS) did not increase fracture risk in children with asthma according to new data from a retrospective cohort analysis presented at the 

 2026 Annual Meeting held in Philadelphia, Pennsylvania on February 27-March 2.

The study included more than 210,000 pediatric asthma patients in the TriNetX United States Collaborative Network. Investigator Lynchi Nguyen, medical student at John Sealy School of Medicine, University of Texas Medical Branch in Galveston, sat down with 

during the meeting to discuss the findings. 

Nguyen emphasized that children treated with short-acting beta agonist (SABA) monotherapy had an 18% higher fracture risk compared with those receiving ICS-only regimens (RR, 1.18; 95% CI, 1.11–1.26). No significant differences in fracture risk were observed between ICS + LABA therapy and SABA-only treatment (RR, 1.05; 95% CI, 0.95–1.15), or between ICS + LABA and ICS-only regimens (RR, 0.97; 95% CI, 0.86–1.09).

The findings, which focused specifically on pediatric-relevant fractures, including Salter-Harris, torus, greenstick, and bent bone fractures occurring at least one year after medication initiation, directly address a longstanding patient concern in pediatric asthma management. While systemic corticosteroids are known to adversely affect bone density in growing children, inhaled corticosteroids have often been viewed with similar suspicion by families and even some clinicians.

Nguyen explained that this misconception may contribute to persistent reliance on SABA monotherapy, despite international guidelines that recommend early incorporation of ICS-containing regimens and movement toward SMART therapy strategies. The new data reinforce that ICS use does not confer the skeletal risks associated with systemic steroids and may even be protective, potentially by reducing exacerbations and limiting systemic steroid bursts.

Beyond reassuring families, the study also offers clinicians flexibility in treatment selection. Because no fracture risk differences were seen between ICS-only and ICS + LABA regimens, providers can tailor therapy based on access, cost, insurance coverage, and disease severity without concern for differential skeletal effects.

Looking ahead, Nguyen suggested that future research should shift toward examining prescribing trends and adherence patterns to determine whether safety data such as these are translating into greater guideline adherence. The larger goal is clear: improving asthma outcomes by confidently incorporating ICS early and consistently in pediatric care.

“If patients are getting diagnosed at a young age, there shouldn't be any hesitancy to start [ICS, or] worrying if this will affect their growth, worrying about their bone density or bone health. I think our study can help clarify that there is no proven increased risk of, you know, detrimental effects to bone health,” Nguyen said.

Nguyen had no relevant disclosures to report.

Reference
Nguyen L, Lee A, Carmichael K, Acevado JA. Fracture Risk Among Pediatric Asthma Patients Treated With Inhaled Corticosteroids: A Retrospective Cohort Study. Presented at: AAAAI 2026 Annual Meeting, February 27-March 2, Philadelphia, Pennsylvania. Poster #L04

Nguyen discussed how her study findings can help alleviate inhaled corticosteroid hesitancy for families.