Biosimilar Laronidase Shows Comparable Efficacy to Reference Drug in MPS I Patients
核心洞察
A phase III crossover study in Iran demonstrated that biosimilar laronidase (CinnaGen) maintained stable urinary GAG levels comparable to reference Aldurazyme in 12 MPS I (搜索) patients over 24 weeks.
Both treatments showed similar enzyme activity profiles and safety outcomes, with no clinically meaningful differences in 6-minute walking test or forced vital capacity results.
The biosimilar maintained therapeutic efficacy without significant clinical deterioration, supporting its potential as a more affordable alternative to the reference enzyme replacement therapy.
Two recent clinical studies provide compelling evidence for enzyme replacement therapy options in mucopolysaccharidosis type I (搜索) (MPS I (搜索)), including the first comparative evaluation of a biosimilar laronidase and confirmatory safety data from Chinese patients.
Biosimilar Demonstrates Therapeutic Equivalence
A phase III crossover study conducted across four Iranian centers evaluated the efficacy and safety of biosimilar laronidase (CinnaGen) compared to reference Aldurazyme in 12 MPS I (搜索) patients aged 5-18 years. The study employed a sequential design where patients received Aldurazyme for 12 weeks followed by the biosimilar for another 12 weeks, both at the standard dose of 0.58 mg/kg.
The primary endpoint comparing mean urinary glycosaminoglycan (uGAG) levels showed the biosimilar maintained therapeutic efficacy. Mean uGAG levels were 220.47 ± 177.13 CPC unit/g creatinine after Aldurazyme treatment and 270.02 ± 111.55 CPC unit/g creatinine after biosimilar treatment. Despite the numerical increase, researchers noted no corresponding clinical deterioration in patients' physical function or respiratory capacity.
"Although there were fluctuations in uGAG levels, Laronidase (CinnaGen) was able to effectively maintain the uGAG levels stable, as the magnitude of the increase in uGAG levels was not clinically considerable," the investigators reported.
Functional Outcomes Show Stability
Secondary endpoints supported the biosimilar's therapeutic maintenance. The 6-minute walking test results increased from 328.22 ± 98.69 meters at week 12 to 360.20 ± 98.11 meters at week 24. Predicted forced vital capacity improved from 57.50 ± 16.53% to 70.56 ± 35.01% over the same period, though researchers deemed these changes not clinically meaningful given the absence of consistent improvements in daily functioning.
Enzyme activity assays conducted at the final visits of each treatment period revealed comparable pharmacokinetic profiles. Prior to infusion, enzyme activity was undetectable in all patients. Following Aldurazyme infusion, mean enzyme activity levels were 36.06 ± 14.06 μmol/h/L immediately post-infusion, declining to 17.49 ± 16.00 and 14.08 ± 19.04 at 30 and 90 minutes respectively. The biosimilar showed similar patterns with levels of 33.27 ± 16.00, 18.35 ± 12.55, and 8.75 ± 10.96 at corresponding timepoints.
Safety Profiles Remain Consistent
Safety analysis revealed no significant differences between treatments. During the 24-week study, 30 adverse events were reported, with most assessed as grade 1 or 2 and attributed to underlying disease rather than treatment. Nasopharyngitis was the most common adverse event, reported by five patients during Aldurazyme treatment and four during biosimilar treatment.
Two serious adverse events occurred, including one death at week 9 during the Aldurazyme period, which investigators attributed to disease progression rather than treatment. The patient had experienced airway disorders and peripheral edema, with underlying MPS I (搜索) conditions progressing to pulmonary hypertension, pneumonia, and obstructive airways disorder.
Chinese Study Confirms Established Safety Profile
A separate phase IV post-marketing surveillance study in China provided additional safety and efficacy data for laronidase in 12 Chinese MPS I (搜索) patients. All participants had attenuated forms of MPS I, with an average age of 13.8 ± 7.7 years.
The study demonstrated substantial reductions in urinary GAG levels, with an average percentage change of -64.61% ± 26.90% from baseline to week 26. Continuous decreases were observed throughout the treatment period, with reductions of -32.23% at week 2, -55.21% at week 4, and -59.79% at week 8.
Liver volume showed an average reduction of 13.24% ± 7.86% from baseline to week 26. The safety profile remained consistent with previous studies, with 91.7% of participants experiencing treatment-emergent adverse events, mostly mild to moderate in intensity.
Clinical Implications for Rare Disease Treatment
The Iranian biosimilar study addresses a critical need in rare disease therapeutics, where traditional equivalency studies face ethical and logistical challenges due to limited patient populations. The researchers noted that formal statistical analysis was not feasible due to the small sample size of 12 patients, but the descriptive analysis provided meaningful clinical evidence.
"Due to the rarity and genetic complexity of MPS I (搜索), we were able to enroll only 12 patients in this study, which resulted in considerable limitations in statistical power," the investigators acknowledged. "The main aim of this study was to demonstrate whether the biosimilar Laronidase preserves the clinical effects of Aldurazyme."
The biosimilar laronidase, developed by CinnaGen Company and expressed in Chinese Hamster Ovary cell lines like the reference product, underwent comprehensive analytical characterization including structural integrity, biological activity, and glycosylation profiles before clinical testing.
Both studies highlight the ongoing importance of enzyme replacement therapy in MPS I (搜索) management, particularly given the high cost of reference products and the need for lifelong treatment in this progressive, multi-organ disorder affecting approximately 1 in 100,000 to 1 in 500,000 live births globally.