In the Press


Chiesi Global Rare Diseases Presents Long-Term Results from Phase 3 BALANCE and BRIGHT Studies in Fabry Disease at the 19th Annual WORLDSymposium™ Research Meeting

24 February 2023

- Company also presents insights from the SPARKLE registry in alpha-mannosidosis that highlight a delay in diagnosis, identify the most frequent genetic MAN2B1 variant in enrolled participants, and report on real-world clinical profiles.

BOSTON, February 24, 2023
– Chiesi Global Rare Diseases, a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people living with rare diseases, today announced the oral presentation of long-term results from the Phase 3 BALANCE and BRIGHT studies that evaluated PRX-102 (pegunigalsidase alfa), an investigational, plant cell culture-expressed, and chemically-modified, stabilized version of the recombinant α Galactosidase A enzyme for the proposed treatment of Fabry disease, at the 19th Annual WORLDSymposium™ Research Meeting that is being held February 22–26, 2023 in Orlando.

The company is also announcing the presentation at WORLDSymposium of insights on the baseline characteristics, genetics, and enzymatic activity of patients with alpha-mannosidosis who are enrolled in the SPARKLE registry, an ongoing post-authorization study in Europe designed as a non-interventional observational study following participants for up to 15 years.

“As a family business, and as a certified benefit corporation, Chiesi Global Rare Diseases is invested in and focused on the long-term support of rare disease patients and their communities,” said Giacomo Chiesi, head of Chiesi Global Rare Diseases. “We are pleased to participate in the annual WORLDSymposium and are especially proud that our long-term clinical research in Fabry disease is being recognized in multiple oral presentations. PRX-102 has been extensively studied for Fabry disease in a clinical trial setting, as more than 140 patients have participated in a comprehensive clinical trial program with more than seven years of follow up. In addition, we now have an opportunity to share insights from the SPARKLE registry, a program that is positioned to significantly advance our knowledge of the ultra-rare disorder alpha-mannosidosis.”

Two oral presentations are reviewing the long-term results from the Phase 3 BALANCE and BRIGHT studies in Fabry disease. One of the oral presentations is featuring two-year results from the randomized, double-blind, BALANCE study designed to assess noninferiority of PRX-102 versus agalsidase beta in adult Fabry disease patients. In total, 77 patients received PRX-102 (n=52) or agalsidase beta (n=25). PRX-102 showed noninferiority to agalsidase beta based on the median estimated glomerular filtration rate (eGFR) annualized slope, a key measure of Fabry disease progression. The difference in median eGFR slope between PRX-102 vs. agalsidase beta was -0.36 mL/min/1.73m2/year, with the lower bound of the CI (95% CI: -2.44, 1.73) meeting the prespecified noninferiority margin.

The second oral presentation is featuring two-year interim results from the ongoing open-label BRIGHT51 extension study that is designed to evaluate the safety and efficacy of 2.0 mg/kg of PRX-102 administered every four weeks in adults with Fabry disease for up to four years. In total, 29 adults (23 male, 6 female; mean age 40.9 years) were enrolled in BRIGHT51 at the time of the analysis.

Following the recent U.S. Food & Drug Administration (FDA) approval of Lamzede® (velmanase alfa-tycv), developed by Chiesi Global Rare Diseases for the treatment of non-central nervous system manifestations of alpha-mannosidosis in adult and pediatric patients (see Full Prescribing Information and Boxed Warning), the company is also presenting insights from the SPARKLE registry that was launched in 2019 and is designed to follow up to 100 patients with the ultra-rare disorder for up to 15 years.  

In a poster presentation, Nathalie Guffon, M.D., Departmental Head at the Reference Centre of inherited metabolic disease in Femme Mère Enfant Hospital, Hospices Civils of Lyon, France, is reporting a descriptive analysis of baseline characteristics of all currently enrolled patients in the SPARKLE registry. In total, 59 patients were enrolled at 23 European sites at the time of the analysis.

  • Mean ages of first alpha-mannosidosis manifestation and diagnosis were 1.9±3.3 (median 1.0 [0–15]) and 8.4±10.5 (median 4.0 [0–50]) years, respectively, representing a 6.5-year delay in diagnosis.
  • A relatively even distribution of participants had compound heterozygous (44%) and homozygous (47%) MAN2B1 pathogenic variants.
  • The pathogenic variant c.2248C>T was the most common in both compound heterozygous and homozygous participants.
  • All participants with available alpha-mannosidase activity data had low enzymatic activity, with a mean residual activity of 2.5%.
  • Future analyses may provide further insights on the safety and efficacy of enzyme replacement therapy, and may also better inform disease knowledge, potentially enabling more accurate and timely diagnoses.

In a separate poster, Nicole Muschol, M.D., Senior Physician at the International Center for Lysosomal Disorders (ICLD) at the University Medical Center Hamburg-Eppendorf in Germany reports on real-world clinical profiles of patients with alpha-mannosidosis in the SPARKLE registry. In this analysis, patients with alpha-mannosidosis had numerous signs and symptoms impacting multiple body systems, which further confirms the high burden of disease they experience. While cognitive disability, hearing impairment or loss, and dysmorphic facial features are frequently reported in alpha-mannosidosis, heart and lung abnormalities are not as commonly associated with the disease but may raise suspicion of alpha-mannosidosis and can indicate a need for additional evaluations.

In addition to data from the SPARKLE registry, Dr. Guffon is also presenting an analysis that compared compliance and infusion-related reactions (IRRs) between home and hospital settings in a clinical trial. In the clinical trial, 13 patients received a total of 2,782 hospital infusions. After receiving 1,243 hospital infusions, eight patients elected to receive home infusions and completed an additional 262 infusions at home. In SPARKLE, 764 hospital infusions and 107 home infusions were received by 17 and four patients, respectively.

Important Safety Information

Lamzede® (velmanase alfa-tycv) is indicated for the treatment of non-central nervous system manifestations of alpha-mannosidosis in adult and pediatric patients.

Important Safety Information

Hypersensitivity Reactions Including Anaphylaxis
Patients treated with Lamzede have experienced hypersensitivity reactions, including anaphylaxis. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during Lamzede administration. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue Lamzede immediately and initiate appropriate medical treatment. In patients with severe hypersensitivity reaction, a desensitization procedure to Lamzede may be considered.

Considerations Due to Hypersensitivity Reactions and/or Infusion-Associated Reactions (IARs)
Prior to Lamzede administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Inform patients and caregivers of the signs and symptoms of hypersensitivity reactions and IARs and instruct them to seek medical care immediately if such symptoms occur.

  • If a severe hypersensitivity reaction (including anaphylaxis) or severe IAR occurs, immediately discontinue Lamzede administration and initiate appropriate medical treatment.
  • In the event of a mild to moderate hypersensitivity reaction or a mild to moderate IAR, consider temporarily holding the infusion for 15 to 30 minutes, slowing the infusion rate to 25% to 50% of the recommended rate, and initiating appropriate medical treatment.

Hypersensitivity Reactions Including Anaphylaxis
Anaphylaxis and severe hypersensitivity signs and symptoms included cyanosis, hypotension, emesis, urticaria, erythema, facial swelling, pyrexia, and tremor.

Infusion-Associated Reactions (IARs)
The most frequent symptoms of IARs that occurred in >10% of the population were pyrexia, chills, erythema, vomiting, cough, urticaria, rash, and conjunctivitis.

Females of Reproductive Potential
Advise females of reproductive potential to use effective contraception during treatment and for 14 days after the last dose if Lamzede is discontinued. For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment with Lamzede.

Embryo-Fetal Toxicity
Based on findings from animal reproduction studies, Lamzede may cause embryo-fetal harm when administered to a pregnant female.

Common Adverse Reactions
The most common adverse reactions (incidence >20%) are hypersensitivity reactions including anaphylaxis, nasopharyngitis, pyrexia, headache, and arthralgia.
Please see Full Prescribing Information.

About Fabry Disease

Fabry disease is a rare, progressive, potentially life-threatening lysosomal storage disorder that leads to the progressive accumulation of abnormal deposits of a fatty substance in the lysosomes throughout a person’s body. It is a multisystemic organ disease and patients experience a wide range of signs and symptoms including episodes of pain, impaired peripheral sensation, and eventually end-organ failure of the kidneys, heart, and the cerebrovascular system. Fabry disease occurs in one in 40,000 to 60,000 people.

About Alpha-mannosidosis

Alpha-mannosidosis is an ultra-rare genetic disorder that begins in childhood and progresses through adulthood. It is characterized by a deficiency of the enzyme alpha-mannosidase that results in the body's cells being unable to properly break down certain groups of complex sugars. The buildup of sugars can affect many parts of the body's organs and systems. Effects of the disease vary significantly from person to person and progress over time. Symptoms may change as a patient gets older and can include recurrent chest and ear infections, hearing loss, distinctive facial features, muscle weakness, skeletal and joint abnormalities, visual abnormalities, or cognitive abnormalities. The prevalence of alpha-mannosidosis is approximately 1/500,00 to 1/1,000,000.


About Chiesi Global Rare Diseases

Chiesi Global Rare Diseases is a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people affected by rare diseases. As a family business, Chiesi Group strives to create a world where it is common to have a therapy for all diseases and acts as a force for good, for society and the planet. The goal of the Global Rare Diseases unit is to ensure equal access so as many people as possible can experience their most fulfilling life. The unit collaborates with the rare disease community around the globe to bring voice to underserved people in the health care system. For more information visit


About Chiesi Group

Chiesi is an international, research-focused biopharmaceuticals group that develops and markets innovative therapeutic solutions in respiratory health, rare diseases, and specialty care. The company’s mission is to improve people’s quality of life and act responsibly towards both the community and the environment.

By changing its legal status to a Benefit Corporation in Italy, the US, and France, Chiesi’s commitment to create shared value for society as a whole is legally binding and central to company-wide decision-making. As a certified B Corp since 2019, we’re part of a global community of businesses that meet high standards of social and environmental impact. The company aims at becoming net-zero by 2035.

With over 85 years of experience, Chiesi is headquartered in Parma (Italy), operates in 30 countries, and counts more than 6,000 employees. The Group’s research and development centre in Parma works alongside 6 other important R&D hubs in France, the US, Canada, China, the UK, and Sweden.
For further information please visit

Chiesi Global Rare Diseases Media Contact
Adam Daley
Berry & Company Public Relations

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