Category: 3. Business

The maternity fashion retailer Seraphine, whose clothes were worn by the Princess of Wales during her three pregnancies, has ceased trading and entered administration.

Consultancy firm Interpath confirmed to the BBC on Monday that it had been appointed as administrators by the company and that the “majority” of its 95 staff had been made redundant.

It said the brand had experienced “trading challenges” in recent times with sales being hit by “fragile consumer confidence”.

The fashion retailer was founded in 2002, but perhaps hit its peak when Catherine wore its maternity clothes on several occasions, leading to items quickly selling out.

Prior to the confirmation that administrators had been appointed, which was first reported by the Financial Times, Seraphine’s website was offering discounts on items as big as 60%. Its site now appears to be inaccessible to shoppers.

The main job of administration is to save the company, and administrators will try to rescue it by selling it, or parts of it. If that is not possible it will be closed down and all its saleable assets sold.

Will Wright, UK chief executive of Interpath, said economic challenges such as “rising costs and brittle consumer confidence” had proved “too challenging to overcome” for Seraphine.

Interpath said options are now being explored for the business and its assets, including the Seraphine brand.

The retailer’s flagship store was in Kensington High Street, London, but other well-known shops, such as John Lewis and Next, also stocked its goods.

The rise in popularity of Seraphine, driven in part by Royalty wearing its clothes, led to the company listing on the London Stock Exchange in 2021, before being taking back into private ownership in 2023.

Interpath said in April this year, the company “relaunched its brand identity, with a renewed focus on form, function and fit”.

“However, with pressure on cashflow continuing to mount, the directors of the business sought to undertake an accelerated review of their investment options, including exploring options for sale and refinance,” a statement said.

“Sadly, with no solvent options available, the directors then took the difficult decision to file for the appointment of administrators.”

Staff made redundant as a result of the company’s downfall are to be supported making claims to the redundancy payments service, Interpath added.

The first half of 2025 marked a dynamic period in pulmonology, with major FDA milestones, promising trial readouts, and continued momentum in precision medicine for respiratory conditions. Most notably, the FDA granted landmark approval to mepolizumab as the first biologic for eosinophilic COPD, signaling a shift toward more targeted treatment for a challenging COPD phenotype. Other regulatory progress included FDA acceptance of a gene therapy BLA for recurrent respiratory papillomatosis, an ultrarare disease with no approved treatments, and encouraging steps toward new therapies for pulmonary arterial hypertension and progressive pulmonary fibrosis.

Meanwhile, clinical pipelines produced a mix of breakthroughs and setbacks. Positive results for TPIP and brensocatib suggested new hope for patients with PAH and bronchiectasis—2 historically underserved populations. Nerandomilast also showed statistically significant benefit in progressive pulmonary fibrosis, potentially expanding options for this debilitating disease. However, tezepelumab failed to meet its endpoint in a COPD trial, underscoring the complexity of inflammation-driven phenotypes.

Check out this H1 2025 pulmonology month in review for a recap of HCPLive’s coverage of the top pulmonology news and research from the past few months:

Regulatory Actions in H1 2025

FDA Approves Mepolizumab for Eosinophilic COPD

On May 22, the FDA has approved mepolizumab (Nucala) as an add-on maintenance treatment for patients with COPD with an eosinophilic phenotype. In the phase 3 MATINEE trial, mepolizumab demonstrated a statistically significant and clinically meaningful 21% reduction in the annualized rate of moderate or severe exacerbations (0.80 events per year) compared to placebo (1.01 events per year; rate ratio, 0.79; 95% CI, 0.66 to 0.94; P = .01), successfully meeting the primary endpoint.

Related content: Expanding Precision Medicine in COPD With Mepolizumab, with Frank Sciurba, MD

FDA Accepts BLA for PRGN-2012 for Recurrent Respiratory Papillomatosis

On February 25, the FDA accepted Precigen, Inc.’s BLA for PRGN-2012 (zopapogene imadenovec), an investigational gene therapy targeted for adults with recurrent respiratory papillomatosis (RRP), a rare disease that requires repeated surgeries with no current therapeutic alternative. A Prescription Drug User Fee Act (PDUFA) action date of August 27, 2025, was set, with no plans to hold an advisory committee meeting.

H1 Data Readouts

Merck Halts Phase 3 HYPERION Trial of Sotatercept for Final Analysis

On January 30, Merck halted the Phase 3 HYPERION trial evaluating sotatercept-csrk (WINREVAIR) versus placebo in adults with recently diagnosed PAH and plans to proceed with the final analysis. Merck indicated the decision to stop HYPERION before its scheduled end date was based on positive data from the interim analysis of ZENITH and an overall review of data from the sotatercept clinical trial program.

Tezepelumab Fails Study Endpoint of Reducing Moderate-to-Severe COPD Exacerbations

Tezepelumab was not seen to reduce the annualized rate of moderate or severe COPD exacerbations, thus failing the primary endpoint of COURSE, a phase 2a trial (NCT04039113). Singh and colleagues found that the annualized rate of moderate or severe COPD exacerbations represented a nonsignificant change and thus did not meet the trial’s primary endpoint.

Nerandomilast Meets Primary Endpoint in Improving FVC in Progressive Pulmonary Fibrosis

Nerandomilast met the primary endpoint in the Phase 3 FIBRONEER-ILD trial, significantly improving forced vital capacity (FVC) among individuals with progressive pulmonary fibrosis (PPF), compared with placebo. Based on these findings, Boehringer Ingelheim announced plans to submit an NDA for nerandomilast to the FDA.

Brensocatib Improved Outcomes, Slowed Decline in People With Bronchiectasis
In April, Brensocatib showed efficacy in reducing pulmonary exacerbations and slowing disease progression in patients with non-cystic fibrosis bronchiectasis. The positive results from the Phase 3 trial suggest brensocatib could become a novel therapeutic option for this underserved population.​

Related content: Investigating Brensocatib, Potential First Treatment for Bronchiectasis, with James Chalmers, MBChB, PhD

TPIP Boasts Significant Outcome Improvements for PAH in Phase 2b

In June, Insmed announced positive phase 2b results for treprostinil palmitil inhalation powder (TPIP), meeting its primary endpoint of significantly reducing pulmonary vascular resistance in patients with pulmonary arterial hypertension (PAH). Based on findings from a randomized, placebo-controlled trial, TPIP treatment led to notable improvements in exercise capacity and biomarkers of heart strain, supporting its potential as an effective once-daily prostanoid therapy. Safety analysis showed TPIP was generally well tolerated despite higher rates of common prostanoid-related adverse events like cough and headache. Insmed plans to initiate phase 3 trials for TPIP in PAH and pulmonary hypertension associated with interstitial lung disease starting later this year and into early 2026.

Story Continues

Panitumumab (Vectibix) combined with FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) or modified FOLFOX6 (mFOLFOX6; leucovorin, fluorouracil, and oxaliplatin) did not elicit clinically meaningful responses in previously untreated patients with liver-limited, RAS/BRAF wild-type unresectable metastatic colorectal cancer (mCRC), failing to meet the primary end point of the phase 2 PANIRINOX-UCGI28 trial (NCT02980510; EudraCT 2016-001490-33), data from which were presented at the 2025 ESMO Gastrointestinal Cancers Congress.¹

In the per-protocol population, among patients with liver-limited disease who received panitumumab plus FOLFIRINOX (n = 66), the complete response (CR) rate was 27.3% (95% CI, 17.0%-39.6%), the overall response rate (ORR) was 90.9%, and the early tumor shrinkage rate was 86.4%. The median depth of response was –78.9% (Q1-Q3, –100% to –58.2%), and the R0 resection rate was 34.8%.

Among patients with liver-limited disease who received panitumumab plus mFOLFOX6 (n = 34), the CR rate was 23.5% (95% CI, 10.7%-41.2%), the ORR was 91.2%, and the early tumor shrinkage rate was 76.5%. The median depth of response was –72.4% (Q1-Q3, –100% to –44.6%), and the R0 resection rate was 38.2%.

“Given that and the rest of our results, we can’t support the use of an intensified chemotherapy backbone in combination with anti-EGFR [therapy] in this setting, regardless of the disease extension,” Thibault Mazard, MD, PhD, stated in the presentation.

Mazard is a medical oncologist specializing in gastrointestinal and head and neck cancer at the Institut du Cancer de Montpellier Val d’Aurelle in France.

Trial Design

The multicenter, open-label, noncomparative, randomized PANIRINOX-UCGI28 trial enrolled patients with unresectable mCRC who were deemed to have curative-intent disease. Patients needed to be previously untreated except for fluoropyrimidine in the adjuvant setting, be 18 to 75 years of age, have an ECOG performance status of 0 or 1, and have RAS/BRAF V600E wild-type disease according to Intplex circulating tumor DNA (ctDNA) analysis.

“PANIRINOX is the first interventional study [that] used [prospective] ctDNA analysis to assess patient eligibility for anti-EGFR treatment before first line,” Mazard noted.

Stratum 1 (n = 108) included patients with liver-limited disease. Stratum 2 (n = 111) included those with non–liver-limited disease. Patients in each stratum were randomly assigned 2:1 to receive FOLFIRINOX plus panitumumab for a maximum of 12 cycles (arms A) or mFOLFOX6 plus panitumumab for a maximum of 12 cycles (arms B).

The primary end point was CR rate, defined as the complete disappearance of metastatic lesions per RECIST 1.1 criteria and CEA level normalization (if applicable) after a maximum of 12 cycles of chemotherapy. Each CR needed to be confirmed and centrally reviewed. CR could be achieved with chemotherapy or a multimodal approach consisting of methods such as surgical resection, radiofrequency, cryoablation, and radiation therapy.

Results from stratum 2 were initially presented at the 2023 ESMO Congress.

Baseline Characteristics

From October 2017 to August 2023, 574 patients were assessed for eligibility across 22 centers. In total, 96.7% of patients had blood samples complying with quality control criteria, and 46.3% of patients had RAS/BRAF V600E–mutated disease. Accordingly, 219 patients were randomly assigned and selected for either stratum.

In the intention-to-treat (ITT) population of stratum 1, the median age was 60 years (range, 31-75) in arm A (n = 74) and 60 years (range, 34-73) in arm B (n = 34). Most patients in both arms were male (64% vs 74%), had primary left-sided tumors (85% vs 85%), and had synchronous metastases (94% vs 96%). Furthermore, 64% and 47% of patients in each respective arm had an ECOG performance status of 0.

Across both arms in the ITT population of stratum 2, the median age was 63 years (range, 32-80). Most patients were male (60%), had an ECOG performance status of 0 (57%), had primary left-sided tumors (78%), had synchronous metastases (86%), and had more than 1 Nb metastatic site (79%). Additionally, liver, lung, and peritoneal involvement was present in 68%, 56%, and 23% of patients, respectively.

Notably, across both strata, similar characteristics were reported in the per-protocol population.

Additional Efficacy Findings

“In stratum 1, the progression-free survival [PFS] and overall survival [OS] were superimposable between the arms,” Mazard explained. “In stratum 2, it was the same tendency for PFS, but when you look at the OS curves, the experimental arm [appeared] to do better.”

At a median follow-up of longer than 35 months, in the per-protocol population of stratum 1, the median PFS was 10.7 months (95% CI, 9.7-12.7) in arm A and 11.2 months (95% CI, 9.3-12.6) in arm B (HR, 0.86; 95% CI, 0.55-1.34; log-rank P = .5127). In the per-protocol population of stratum 2, the median PFS was 9.1 months (95% CI, 8.1-11.7) in arm A and 9.0 months (95% CI, 7.5-11.9) in arm B (HR, 0.98; 95% CI, 0.61-1.57; log-rank P = .9312).

Regarding OS, in the per-protocol population of stratum 1, the median OS was not reached (NR; 95% CI, 33.7 months-NR) in arm A and NR (95% CI, 28.2 months-NR) in arm B (HR, 0.97; 95% CI, 0.49-1.94; log-rank P = .9341). In the per-protocol population of stratum 2, the median OS was 34.7 months (95% CI, 26.4-NR) in arm A and 25.9 months (95% CI, 17.8-NR) in arm B (HR, 0.71; 95% CI, 0.39-1.30; log-rank P = .2639).

Safety Data

The most commonly observed grade 3 or higher treatment-related adverse effects in arms A vs B, respectively, were diarrhea (34% vs 12%), peripheral neuropathy (19% vs 9%), and skin toxicities (16% vs 22%).

ctDNA Analysis Findings

Investigators performed a ctDNA analysis that included treated patients from both arms of both strata (n = 216) and found no differences in response according to mutation allele frequency (MAF) vs total ctDNA concentration. At baseline, 138 patients were RAS/BRAF V600E wild-type. In this population, the CR rate was 19.6% (95% CI, 13.3%-27.2%), and the ORR was 79.7% (95% CI, 72.0%-86.1%). Additionally, 78 patients had a RAS/BRAF MAF of 0.5% or lower. In this population, the CR rate was 12.8% (95% CI, 6.3%-22.3%), and the ORR was 87.2% (95% CI, 77.7%-93.7%).

Furthermore, many patients had RAS/BRAF wild-type ctDNA at end of treatment (EOT). After a median of 189 days (range, 58-455) of treatment, among evaluable patients who had RAS/BRAF wild-type disease at baseline (n = 82), 78% had persistent wild-type disease, and 22% had RAS/BRAF-mutated disease. Among evaluable patients who had a RAS/BRAF MAF of 0.5% or lower (n = 50), 16% and 84% had RAS/BRAF-persistent and wild-type disease, respectively.

“Our findings…confirm the relevance of using ctDNA analysis to molecularly select patients before first-line [therapy], even if the identification of RAS or BRAF MAF with our method may not impact treatment activity.”

Disclosures: Mazard reported serving on advisory boards for Pierre Fabre, MSD, Servier, and Takeda; serving as an invited speaker for Pierre Fabre, Servier, and Astra Zeneca; participating in a writing engagement with Galapagos; serving as a coordinating principal investigator for Amgen; receiving travel grants from Pierre Fabre, Merck, Serono, Sanofi, MSD, Takeda, and Servier; and serving in an advisory role for Inca.

Reference

1. Mazard T, Ghiringhelli F, Nguyen L, et al. Panitumumab (P) + FOLFIRINOX or mFOLFOX6 in unresectable metastatic colorectal cancer (mCRC) patients (pts) with RAS/BRAF wild-type (WT) tumor status from circulating DNA (cirDNA): final results of the randomised phase II PANIRINOX-UCGI28 study. Presented at: 2025 ESMO Gastrointestinal Cancers Congress; July 2-5, 2025; Barcelona, Spain. Abstract 7MO.

New long-term data from the phase 3 REACH3 study (NCT03112603) demonstrate that ruxolitinib (Jakafi) provides sustained efficacy and a manageable safety profile over 3 years in patients with steroid-refractory/dependent chronic graft-vs-host-disease (SR/D-cGVHD). The findings underscore ruxolitinib’s role as an effective treatment option for this challenging patient population, confirming and extending the positive results of the primary 24-week analysis.

The study, which randomized 329 patients (165 to ruxolitinib, 164 to best available therapy [BAT]), showed a significantly longer median failure-free survival (FFS) with ruxolitinib at 38.4 months compared with 5.7 months for BAT (HR 0.36; 95% CI, 0.27-0.49).This sustained benefit was evident at 36 months, with a 56.5% probability of FFS for patients treated with ruxolitinib vs 18.2% for those on BAT. Similarly, the median duration of response (DOR) was not reached for ruxolitinib in contrast to 6.4 months for BAT, indicating a more durable response with the JAK inhibitor.At 36 months, 59.6% of ruxolitinib-treated patients maintained a response, compared with 26.7% in the BAT arm.

Further, study authors noted that, “…ruxolitinib provided clinical benefits whether given as a second- or third-line option, which is consistent with an analysis showing that response was not influenced by the timing of ruxolitinib initiation. However, ruxolitinib is recommended for second-line use for cGVHD.”

cGVHD is a severe complication of allogeneic hematopoietic stem cell transplantation, with corticosteroids serving as the cornerstone of first-line treatment. However, a significant proportion of patients develop steroid refractoriness or dependence, necessitating alternative therapeutic strategies.Ruxolitinib, a potent and selective inhibitor of JAK1 and JAK2, has emerged as a crucial second-line agent for cGVHD, gaining approval based on the initial positive outcomes of the REACH3 trial and subsequently being recommended in clinical guidelines.

The long-term follow-up of REACH3 aimed to evaluate the extended efficacy and safety of ruxolitinib and assess responses in patients who crossed over from BAT to ruxolitinib. The open-label, multicenter study allowed patients initially randomly assigned to BAT to cross over to ruxolitinib after week 24 if their condition warranted.

Overall survival (OS) was not reached in either arm, with no significant difference in the risk of death between the groups (HR, 0.85; 95% CI, 0.54-1.33). The study also reported low rates of nonrelapse mortality (NRM) and malignancy relapse/recurrence, with overlapping incidence curves between the 2 arms. Notably, corticosteroid doses declined over the study period in both groups, with 55.3% of the ruxolitinib arm and 36.4% of the BAT arm achieving complete taper-off of corticosteroids. The probability of maintaining a long-term response with ruxolitinib was observed irrespective of baseline organ involvement, including difficult-to-treat organs like the lung and liver.

An important aspect of the study was the crossover analysis, which included 70 patients who switched from BAT to ruxolitinib. In this cohort, the overall response rate (ORR) at week 24 of the crossover period was 50.0%, and the best overall response (BOR) was 81.4%. These response rates were consistent with those observed in the primary analysis of patients initially randomized to ruxolitinib, suggesting that ruxolitinib provides clinical benefits even when initiated as a later-line option. Furthermore, nearly three-quarters of these crossover patients maintained their response for more than 2 years.

Regarding safety, the long-term profile of ruxolitinib remained consistent with previous reports, with no new safety signals identified.The median duration of exposure was significantly longer for ruxolitinib (52.9 weeks) compared with BAT (24.1 weeks). After adjusting for exposure duration, the incidence rates of grade ≥3 adverse events (AEs) and serious AEs were lower in the ruxolitinib arm. Anemia was the most common AE and grade ≥3 AE associated with ruxolitinib, while pneumonia was the most frequent AE leading to discontinuation.

Infections were the most common AEs of special interest, though most were grade 2. The incidence of cytomegalovirus infection was similar across both arms. On-treatment deaths were primarily attributed to cGVHD in both groups. The AE profile in the crossover population mirrored that of the randomized ruxolitinib arm, further supporting its consistent and long-term safety.

REFERENCE:

Zeiser R, Russo D, Ram R, et al. Ruxolitinib in patients with corticosteroid-refractory or corticosteroid-dependent chronic graft-versus-host disease: 3-year final analysis of the phase III REACH3 study. J Clin Oncol. Published online June 25, 2025. doi:10.1200/JCO-24-02477