MG‐K10 in Moderate‐to‐Severe Asthma: Extending the Dosing Interval Without Compromising Efficacy

To the Editor,

We read with great interest the Phase Ib/II study by Xian et al. [1] evaluating MG‐K10, a novel humanized anti‐IL‐4Rα monoclonal antibody (mAb), in Chinese patients with moderate‐to‐severe asthma. The authors are to be commended for demonstrating that both 300 mg every 2 weeks (Q2W) and every 4 weeks (Q4W) regimens significantly improved pre‐bronchodilator FEV1 compared with placebo at Week 12, with LS mean differences of 0.35 L (95% CI, 0.208–0.490) and 0.30 L (95% CI, 0.156–0.441), respectively (both p < 0.0001). Beyond confirming the therapeutic value of IL‐4Rα blockade in a Chinese population, this study raises several points that merit further discussion.

1. The Q4W Regimen: From Pharmacokinetic Engineering to Clinical Convenience

The most clinically consequential finding is the comparable efficacy of the Q4W and Q2W regimens across multiple endpoints. At Week 24, the LS mean differences in FEV1 compared with placebo were virtually superimposable (0.33 L for Q2W; 0.34 L for Q4W), as were the annualized severe exacerbation rates (0.09 vs. 0.10 events/year; relative risks compared with placebo of 0.25 and 0.27, respectively). This stands in clear contrast to dupilumab, the first‐in‐class anti‐IL‐4Rα mAb, which is dosed Q2W as the standard maintenance regimen for asthma, with no validated Q4W dosing schedule to date [2].

Critically, the prolonged dosing interval of MG‐K10 is not an arbitrary schedule but stems from intentional structural engineering: an engineered mutation within the fragment crystallizable (Fc) region confers roughly 10‐fold higher affinity for the neonatal Fc receptor (FcRn) relative to dupilumab. Pharmacokinetically, this modification results in a half‐life and AUC nearly twice those of dupilumab at equivalent doses, as reported in a preceding Phase I study [1]. This rational, structure‐guided dosing strategy translates a molecular binding advantage into a clinically meaningful reduction in annual injections, falling from around 26 to 13 administrations per year.

Less frequent dosing carries notable implications for treatment adherence. Real‐world data consistently show that longer dosing intervals improve persistence with chronic biologic therapies. For asthma, a disease where poor long‐term adherence to injectable treatments is a well‐recognized clinical barrier, the Q4W regimen may deliver benefits beyond those observed in this 24‐week trial [3].

2. Tolerability Signals: Injection‐Site Reactions

The near absence of injection‐site reactions (ISRs) with MG‐K10 is noteworthy. Only one patient (1.7%) in the Q4W group experienced an ISR, while dupilumab trials in asthma patients have reported consistent ISR rates of 15%–18% [2, 4]. The authors attributed this favourable safety profile to MG‐K10's engineered structure and simplified formulation components, yet the exact underlying factors remain unconfirmed. Potential contributors may include differences in excipients, the humanized rather than fully human antibody backbone, less frequent injections, or the relatively small sample size (n = 187). Further dedicated assessment in the ongoing Phase III program (NCT06837922) is therefore warranted, as a sustained lower ISR rate would constitute a valuable tolerability benefit in clinical practice.

3. Biomarker Pharmacodynamics and the ACQ‐5 Discordance

The pharmacodynamic findings are compelling. FeNO and serum TARC levels were maximally suppressed by week 4, with effects sustained through week 24. The authors noted that the reduction in FeNO was more pronounced than that seen with dupilumab, a finding consistent with the robust improvements in FEV1 [1]. If validated, this may indicate more complete or prolonged tissue target engagement. Nonetheless, cross‐trial comparisons of biomarker profiles require careful interpretation due to differences in study populations and laboratory assays.

The lack of significant improvement in ACQ‐5 scores, despite favourable objective outcomes in FEV1 and exacerbation reduction, represents an informative discordance. The authors correctly attributed this to the high variability of patient‐reported outcomes (PROs) and the limited sample size. This observation also highlights a common challenge in the development of asthma biologics. Spirometry and exacerbation endpoints often diverge from patients' subjective symptom perception, especially among those with long‐standing disease and possible interoceptive adaptation [5]. The upcoming Phase III program, with a larger sample size and improved statistical power for PRO analyses, will help clarify this discrepancy.

4. Population Specificity and Generalizability

This study recruited solely Chinese patients across 32 domestic sites (mean age 55.1 years; mean BMI 24.2 kg/m²), whose demographic profiles differ substantially from those in global dupilumab trials, which enrolled younger participants with higher mean BMI [2]. This is a key strength, as it provides dedicated efficacy and safety data for an Asian population and fills an evidence gap previously identified in Asia‐Pacific subgroup analyses of dupilumab [6]. Meanwhile, the ethnic limitation restricts generalizability; bridging studies in other populations will be required to support regulatory approval outside China.

5. Concluding Remarks

In summary, Xian et al. present encouraging evidence that MG‐K10, developed via targeted FcRn engineering, achieves robust clinical efficacy alongside a convenient Q4W dosing schedule, a favourable safety profile, and markedly low ISR rates. Should these results be replicated in the ongoing 52‐week Phase III trial, MG‐K10 will represent a meaningful advance in anti‐IL‐4Rα therapies, translating molecular innovation into practical, patient‐centric clinical benefits.

Author Contributions

Feizhou Zhang: conceived and drafted the correspondence. Lanfang Tang: provided critical revision of intellectual content, supervised the work, and approved the final version for submission. All authors have read and approved the final manuscript and agree to be accountable for all aspects of the work.

Funding

This work was supported by the Innovation Team for the Diagnosis and Treatment of Childhood Asthma and the “Pioneer” and “Leading Goose” R&D Program of Zhejiang Province (Grant No. 2026C02A1117). The funding bodies had no role in the drafting, revision, or decision to submit this correspondence.

Ethics Statement

The authors have nothing to report.

Consent

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

All data discussed in this correspondence are derived from the published article by Xian et al. and the publicly available peer‐reviewed studies cited in the reference list.