BioMarin Studies Treatment Of MPS IVA
November 8, 2012

BioMarin Phase 3 Study Of GALNS For The Treatment Of MPS IVA Meets Primary Endpoint

Connie K. Ho for — Your Universe Online

Advances in medical technology have made it possible for new treatments to be developed. One such example of the development of treatments is work done by BioMarin Pharmaceutical Inc., a company focused on developing and commercializing biopharmaceuticals for serious diseases and other medical conditions. Having met the primary endpoint of change in a six minute distance walk as compared to a placebo at 24 weeks for participants taking in a weekly infusion of GALNS of 2 mg/kg, BioMarin Pharmaceutical Inc. will be submitting marketing applications in 2013.

The randomized, double-blind placebo-controlled study (MOR-004) looked at the effect of two doses of GALNS for patients who were diagnosed with lysosomal storage disorder Mucopolysaccharidosis Type IVA (MPS IVA), otherwise known as Morquio A Syndrome. According to the National MPS Society, children who are diagnosed with MPS IVA do not have the enzyme necessary for splicing the mucopolysaccharides keratan sulfate. As the mucopolysacchardies stay in the body incompletely broken down, it can cause damage to the body´s cells.

Subjects in the study were required to be clinically diagnosed as having MPS IVA. Researchers measured the six-minute walk distance, three-minute chair climb, and urinary Keratan Sulfate. For patients who were given dosages of 2 mg/kg of GALSN every week, they did not show a great deal of change from the baseline as opposed to the placebo. The company is also conducting an extension study, and only a few patients have participated in the study up to the 36 or 48-week points of time. The company plans to submit marketing applications based off of the results of the various studies it is conducting.

"The positive results from this pivotal study will help support GALNS as the first therapy available to help the approximate 3,000 people worldwide suffering from MPS IVA -- a rare, degenerative, life-threatening genetic condition with no available therapy," explained Dr. Hank Fuchs, Chief Medical Officer at BioMarin, in a prepared statement.

In particular, patients who were given doses of 2 mg/kg of GALSN every week improved in the six-minute walk distance during week 12 as compared to the baseline. They continued to improve at week 24 of the study as well. Regarding the secondary endpoint that looked at the three-minute stair climb, patients who were given does of 2 mg/kg of GALSN every week continued to improve and made progress at the 24-week mark of the study. Patients who reached the 36 and 48 week marks also showed sufficient improvement in the three-minute stair climb. Based on the findings, the scientists believe that doses of GALNS boost pulmonary function.

"We are very pleased with the clarity that the MOR-004 study has provided us with respect to the appropriate dosing of GALNS. The weekly 2 mg/kg dose provided a statistically significant and clinically meaningful improvement in the study's primary endpoint, and positive trends toward improvement in other clinically meaningful endpoints, including three-minute stair climb and pulmonary function tests. By contrast, the 2 mg/kg every other week dose was shown to be similar to placebo on the primary and clinical secondary and tertiary endpoints," continued Fuchs in the statement.

Even though the study showed success, some participants in the MOR-004 studied suffered adverse effects. The team of investigators reported that over 25 percent of treated patients had symptoms like cough, headache, nausea, pyrexia, and vomiting. The researchers were able to respond to these situations by modifying the treatments.

"The GALNS clinical program is currently the highest development priority at BioMarin, and this positive Phase 3 study serves as a potentially transformative milestone for the company," noted Jean-Jacques Bienaimé, CEO of BioMarin, in a prepared statement. "We are applying our track record of success in developing novel treatments for orphan diseases and our existing commercial infrastructure for Naglazyme to bring GALNS to patients as rapidly as we can."

The team of investigators plans to present the complete results of the study at the WORLD Symposium next February. With the National MPS Society and The Carol Ann Foundation/International Morquio Organization, there is more and more awareness about this disease. The Morquio Organization reported that MPS IVA, which is a lysosomal storage disorder (LSDs), can affect approximately one out of 7,7000 newborns. Those diagnosed with the illness usually have a wide range of symptoms and signs.

In the prognosis of MPS IVA, cervical myelopathy, where there is injury to the spinal cord, can develop early in patients as a more severe version of Morquio syndrome. Patients with this form of the disease may not be able to survive in their twenties and thirties, as paralysis, restrictive chest wall movement, and valvular heart disease are factors that can affect the individual. The clinical features of MPS IVA include fatigue, difficulty breathy, sleep apnea, recurring infections, hearing loss, a tendency to fall while walking, corneal clouding, short neck and trunk dwarfism, among other things. Warning signs of the disease that appear during infancy include skeletal deformities, a waddling gate, delayed ability to stand and walk, as well as delay of growth.

Lastly, MPS IV is an inheritable disease, caused by a recessive gene. There is currently no cure for this disease, but there are options for managing and treating problems related to the illness; current treatments include bone marrow transplant/hematopoetic stem cell translation, palliative care, orthopedic surgeries, or physiotherapy.