SAN RAFAEL, California — BioMarin says its Pompe disease therapy Pombiliti plus Opfolda maintained important measures of mobility and helped limit lung-function decline for as long as five years, giving the company new long-term evidence for one of the key rare-disease products it acquired in its $4.8 billion Amicus Therapeutics takeover.
BioMarin presented the new results at the 31st Annual Congress of the World Muscle Society in Hiroshima, Japan, showing extended follow-up from patients with late-onset Pompe disease, or LOPD, who continued treatment after participating in the original Phase 3 PROPEL study.
The analysis followed 82 patients who received Pombiliti plus Opfolda continuously from the beginning of PROPEL.
Among them, 62 had already been treated with enzyme-replacement therapy before entering the study, while 20 were treatment-naïve at baseline.
The long-term results are important because Pompe disease is progressive.
Even when patients receive treatment, muscle weakness and respiratory deterioration can worsen over time.
BioMarin therefore argues that keeping mobility relatively stable and slowing lung-function loss over several years is clinically meaningful.
Walking Ability Remained Relatively Stable in Previously Treated Patients
For patients who had already been receiving enzyme-replacement therapy before joining PROPEL, BioMarin reported a mean 0.7% improvement from baseline in percent-predicted six-minute walk distance after five years.
The six-minute walk test measures how far a patient can walk within six minutes and is widely used to assess functional endurance in neuromuscular diseases.
The result is significant because late-onset Pompe disease normally causes progressive weakness.
BioMarin’s interpretation is that maintaining mobility close to baseline over five years suggests durable treatment benefit.
The ERT-experienced patients had already been receiving enzyme therapy for an average of 7.6 years before entering the study, making them a particularly important group for assessing whether changing therapy could stabilize disease progression.
Treatment-Naïve Patients Showed Larger Walking Gains
The smaller treatment-naïve group showed a substantially larger improvement.
BioMarin reported a mean 10.5% increase in percent-predicted six-minute walk distance through 4.5 years among the 20 patients who had not previously received enzyme-replacement therapy.
That result suggests patients beginning therapy earlier in their treatment journey may have more room for functional improvement.
But there is an important qualification.
The U.S. Food and Drug Administration does not currently approve Pombiliti plus Opfolda for ERT-naïve patients.
Its U.S. indication is for adults with late-onset Pompe disease weighing at least 40 kilograms who are not improving on their current enzyme-replacement therapy.
The FDA has also cautioned that the treatment-naïve subgroup in the original pivotal trial was too small to draw definitive conclusions about effectiveness in that population.
So the long-term treatment-naïve data are scientifically interesting but should not be interpreted as an expansion of the current U.S. label.
Lung Function Declined, but BioMarin Says the Drop Was Limited
Respiratory decline is one of the most serious consequences of Pompe disease.
The condition results from deficiency of the enzyme acid alpha-glucosidase, causing glycogen to accumulate inside muscle cells.
Over time, this can weaken skeletal and respiratory muscles.
In the five-year extension, previously treated patients showed a mean 2.8% decline from baseline in percent-predicted forced vital capacity, or FVC.
The treatment-naïve group showed a mean decline of 4.4% through 4.5 years.
BioMarin characterized those results as relative stabilization of pulmonary function in a disease that would otherwise be expected to progressively weaken breathing muscles.
That distinction matters.
The therapy did not produce a sustained improvement in lung capacity.
The argument is instead that decline was relatively limited over several years.
What Pombiliti and Opfolda Actually Do
Pombiliti and Opfolda work together.
Pombiliti, or cipaglucosidase alfa-atga, is an enzyme-replacement therapy administered intravenously every two weeks.
Opfolda, or miglustat, is an oral enzyme stabilizer taken before the infusion.
Opfolda is designed to stabilize the replacement enzyme in the bloodstream so more active enzyme can reach muscle tissue.
The combination is intended to improve delivery of the therapeutic enzyme into cells where glycogen accumulates.
The FDA approved the combination in September 2023.
The Original Phase 3 Trial Included 123 Patients
The regulatory approval was based primarily on the Phase 3 PROPEL study.
That randomized trial enrolled 123 adults with late-onset Pompe disease across 61 sites in 24 countries.
Of those patients:
95 had previously received enzyme-replacement therapy
and
28 were ERT-naïve.
Patients received either Pombiliti plus Opfolda or an active comparator for 52 weeks.
The FDA’s review showed the combination produced a smaller average decline in sitting forced vital capacity than the comparator group, although the agency notes that conclusions about comparative effectiveness against a U.S.-approved alglucosidase alfa product cannot be drawn directly from the trial.
That makes the new five-year extension particularly valuable from a durability perspective.
The original randomized trial lasted one year.
The latest analysis follows some patients for approximately five times longer.
But the Five-Year Study Has an Important Limitation
The strongest caution is methodological.
The long-term analysis comes from an open-label extension.
That means there was no continuing randomized comparator group followed under the same blinded conditions for the full five years.
Patients also had to remain in the study long enough to contribute long-term data.
That can introduce survivor and selection effects.
People who tolerate and respond to therapy may be more likely to remain in long-term follow-up than those who discontinue treatment.
So the results provide useful evidence about durability among patients who continued therapy.
They do not establish that Pombiliti plus Opfolda is definitively better than every other available Pompe treatment over five years.
The Safety Profile Remained Consistent
BioMarin said no new safety signals emerged in the long-term data.
The combination’s established risks include potentially serious infusion-associated and allergic reactions.
The FDA lists common adverse reactions including:
headache
diarrhea
dizziness
shortness of breath
fever
nausea
and
abdominal pain.
Opfolda also carries pregnancy-related warnings because of potential fetal harm.
Long-term safety therefore remains an important part of treatment decisions, especially because patients with Pompe disease may require therapy for many years.
BioMarin Only Recently Acquired the Drug
The five-year data arrive just months after BioMarin completed its acquisition of Amicus Therapeutics.
BioMarin announced the deal in December 2025 and completed it on April 27, 2026, paying approximately $4.8 billion in equity value.
The acquisition gave BioMarin two important commercial medicines:
Galafold for Fabry disease
and
Pombiliti plus Opfolda for Pompe disease.
BioMarin said the acquisition would significantly expand and diversify its rare-disease revenue base.
The company financed the transaction using existing cash plus approximately $3.7 billion in non-convertible debt.
That makes Pombiliti plus Opfolda more than a medical asset.
It is now a major part of the financial logic behind one of BioMarin’s biggest acquisitions.
The Pompe Market Is Already Competitive
BioMarin is not entering an empty market.
Sanofi has been a dominant player in Pompe disease for years through its enzyme-replacement therapies.
Its newer product, Nexviazyme, or avalglucosidase alfa, is already approved for Pompe disease and is being studied across broader patient groups.
In June, Sanofi reported positive Phase 3 Baby-COMET results in treatment-naïve infants with infantile-onset Pompe disease, saying Nexviazyme met all primary and secondary endpoints.
Sanofi plans to use those results to support a U.S. regulatory application in infantile-onset disease.
That matters because Pompe disease is not one uniform market.
There are major differences between:
infantile-onset Pompe disease,
late-onset disease,
previously treated patients,
and newly diagnosed patients.
BioMarin’s strongest current U.S. position is in adults with late-onset disease who are not improving sufficiently on existing enzyme replacement therapy.
Long-Term Data Could Help BioMarin Compete on Durability
That is why five-year follow-up matters commercially.
Doctors treating a chronic progressive disease want evidence that a therapy works not only for one year but over many years.
A durable five-year dataset can help BioMarin argue that Pombiliti plus Opfolda offers sustained benefit rather than a short-lived improvement.
BioMarin Chief Research and Development Officer Greg Friberg said maintaining motor function while limiting pulmonary deterioration for up to five years is clinically meaningful in a progressive disorder such as LOPD.
That message is likely to become central to BioMarin’s competitive positioning.
Pompe Disease Is Rare — But Treatment Can Be Lifelong
Pompe disease is an inherited lysosomal storage disorder caused by mutations affecting acid alpha-glucosidase.
Without enough functioning enzyme, glycogen accumulates inside muscle cells.
The disease can weaken:
skeletal muscles,
the diaphragm,
respiratory muscles,
and in severe infantile forms, the heart.
Late-onset disease can emerge anywhere from childhood to adulthood.
Progression varies considerably between patients.
Because the underlying genetic defect does not disappear, enzyme-replacement therapy generally needs to continue indefinitely.
That makes long-term treatment durability particularly important.
A therapy that performs well for one year but loses effectiveness over time would offer limited benefit in a lifelong disease.
BioMarin Is Becoming Even More Focused on Rare Genetic Disorders
The Amicus acquisition fits a broader strategic shift.
BioMarin describes itself as a company focused on genetically defined rare diseases and now has nine commercial therapies across multiple conditions.
Its portfolio includes treatments for:
skeletal disorders,
metabolic diseases,
lysosomal storage disorders,
and other genetic conditions.
BioMarin generated about $3.2 billion in revenue in 2025, up 13% from the previous year, before incorporating Amicus’ products into its results.
Pombiliti plus Opfolda and Galafold therefore give the company additional commercial scale while reducing its dependence on any single franchise.
The Acquisition Also Came With Pressure to Deliver
Paying $4.8 billion creates expectations.
BioMarin has already experienced setbacks elsewhere in its portfolio.
Earlier this year, the company said its Phase 3 BMN 401 study in ENPP1 deficiency met only one of two co-primary endpoints and failed to produce meaningful clinical improvement in rickets severity.
BioMarin also voluntarily withdrew hemophilia gene therapy Roctavian from the market after failing to find a buyer, while saying the decision was unrelated to the drug’s safety or efficacy.
Those developments increase the importance of successful commercial franchises elsewhere.
Pompe disease is therefore one of the businesses BioMarin needs to execute well.
The Bigger Question Is Market Expansion
The five-year results strengthen the current treatment story.
But the next commercial question is larger.
Can BioMarin expand use of Pombiliti plus Opfolda beyond patients who are already failing another enzyme-replacement therapy?
The treatment-naïve long-term data are encouraging.
But the FDA currently does not approve the combination for those patients.
Winning a broader label would require additional clinical evidence and regulatory review.
If BioMarin succeeds, the addressable market could grow significantly.
If it does not, the product will remain concentrated primarily among patients switching from established enzyme therapies.
Five Years of Data Strengthen the Story — But Competition Is the Real Test
The newest results give BioMarin something valuable:
time.
Five years of follow-up is meaningful for a progressive rare disease where treatment may continue for decades.
The data suggest that previously treated patients who stayed on Pombiliti plus Opfolda maintained walking performance near baseline while experiencing relatively modest average declines in pulmonary function.
Treatment-naïve patients showed even stronger gains in walking ability, although that population remains outside the current U.S. indication.
But long-term durability is only one part of the commercial equation.
BioMarin still has to convince physicians, insurers and patients that its two-component treatment offers enough benefit to justify switching from established therapies.
And it eventually has to prove whether the encouraging results in treatment-naïve patients can support broader use.
So the five-year results strengthen BioMarin’s scientific case.
The bigger challenge now is turning that durability into market share in a Pompe disease field where competitors are still advancing their own treatments.
