Rare Disease Pipeline Products | Chiesi Global Rare Diseases

Our areas of Focus

Patients are at the beginning and end of our journey—that’s why we apply so much focus to science and innovation. We engage in a wide dialogue beyond treatment to understand the needs of individuals, their families, and the community so we can imbed your voice in our development process. We promise to keep researching, enhancing, and advancing new products, whether internally or through partnerships, so people impacted by rare diseases can find the care they need.

Rare Diseases
In Europe, a disease is rare when it occurs in less than 1 in 2,000 people. A disease can be rare in one region but at the same time can be more common in another region. There are also common diseases with rare variants. Taken together, there are thousands of rare diseases.^1,2

Causes and research
Rare diseases are problematic. Because of their rarity, they can be serious, often chronic, and sometimes progressive. Although almost all hereditary diseases are rare, not all rare diseases have a hereditary origin. For example, there are also very rare infectious diseases, rare autoimmune diseases, and rare forms of cancer.
For a long time, rare diseases haven’t received the same attention as other diseases— for example, cardiovascular disease. This had a large impact on the quantity of research into these diseases, but also on determining policies and development of medicines. For most rare diseases, there is no medicine available, but proper medical care can improve the quality of life and prolong life expectancy.

Diagnosis and treatment
It is often difficult for patients with rare diseases to receive information, to consult the right specialists, or to get diagnosed. Their disease remains often unknown. For patients with a rare disease it can be difficult to receive effective medical treatment. Chiesi Rare Diseases Benelux is committed to the treatment of Alpha-Mannosidosis, Nephropathic Cystinosis, Leber’s Hereditary Optic Neuropathy, Beta-Thalassemia Major, and Fabry.

_{1. Nguengang Wakap S, et al. Eur J Hum Genet 2019.}

_{2. Cairns T, et al. Postgrad Med J 2018;94(1118):709-713.}

Legend

Pre Clinical

Early Clinical

Late Clinical

Approved

DISEASE

DEVELOPMENT STAGE

PRECLINICAL

EARLY CLINICAL

LATE CLINICAL

APPROVED

PARTNER

Leber's Hereditary
Optic Neuropathy

Nephropathic
Cystinosis

Alpha-Mannosidosis

Thalassemia

^**

Sickle Cell Disease or Other Anemias

ADA - SCID

Fabry Disease

^**

(Various)

* Brazil, Canada, and Turkey

** Worldwide

Inborn Errors of Metabolism

Alpha-mannosidosis is a rare genetic disease caused by the impaired function of the lysosomal enzyme alpha-mannosidase.¹ Due to this deficiency, oligosaccharides are only partially broken down and over time they build up in the body, causing increasing damage to cells and leading to medical problems in many body systems.^1,2

Alpha-mannosidosis is a very heterogeneous disease, presenting with a wide range of symptoms: the most frequent are recurrent chest infections and problems with hearing loss, distinctive facial features, cognitive impairment, and progressive muscular weakness. Lack of voluntary coordination of muscle movements and skeletal and joint abnormalities could occur. In adulthood, few patients manage to be completely independent socially, needing help with many activities and possibly requiring a wheelchair.¹

High levels of oligosaccharides in urine is suggestive of alpha-mannosidosis. Testing of the mannosidase enzyme residual activity and genetic analysis are used to confirm the diagnosis.¹ Alpha-mannosidosis is a rare disease, affecting approximately 1 in 1,000,000 babies born worldwide.³

_{1. Malm D, et al., Orphanet Journal of Rare Diseases. 2008, 3:21.}

_{2. Borgwardt L, et al., Orphanet Journal of Rare Diseases. 2015, 10:70.}

_{3. Beck M, et al., Orphanet Journal of Rare Diseases. 2013, 8:88.}

Fabry disease is a lysosomal storage disorder, meaning that a glycosphingolipid called GL-3 accumulates in the lysosomes, causing tissue damage; many cell types are affected.¹

The disease is caused by mutations in the GLA gene, resulting in nonfunctional or dysfunctional alpha-galactosidase A, a lysosomal enzyme. The mutations can be inherited, so multiple family members can have the disease.¹ Fabry disease is a multisystemic disease, affecting many organs, including the heart, kidney and nervous system, resulting in life-threatening complications and a reduced life expectancy. Early signs of the disease start in childhood and adolescence, but it is a progressive, lifelong condition.^1,2

Newborn screening has now been performed in several countries, yielding a prevalence ranging from 1 in 1,368 to 1 in 8,882 births.²

_{1. Wanner C, et al. Mol Genet Metab. 2018;124(3):189-203.}

_{2. Cairns T, et al. Postgrad Med J. 2018;94(1118):709-713.}

Nephropathic cystinosis is the most common and severe form of cystinosis, a metabolic disease characterized by accumulation of the amino acid cystine within lysosomes in the cells, leading to damage in many organs and tissues.^1,2

Nephropathic cystinosis usually presents in early infancy as renal Fanconi syndrome, a serious disorder of the proximal tubules of the kidneys involving excessive excretion of nutrients and minerals such as glucose, amino acids, phosphates, potassium, and sodium. This can lead to excessive urination, resulting in acute dehydration. The loss of nutrients impairs growth and may result in soft, bowed bones. Untreated children will experience complete kidney failure by about the age of 10.¹

Nephropathic cystinosis is not only a renal disorder, but a multisystemic disease that could lead to ocular and neurologic impairment, muscle deterioration, diabetes, thyroid, and infertility in affected men.¹

Transmission is autosomal recessive: 2 altered copies of the gene from both parents are needed to manifest the disease.¹ It is an ultrarare disease, with an estimated incidence of around 1 in 100,000 — 1 in 200,000 live births.¹

_{1. Genetics Home Reference. National Institutes of Health. https://ghr.nlm.nih.gov/condition/cystinosis. Last accessed: December 20, 2019 .}

_{2. Cystinosis Research Network. https://www.cystinosis.org/support-resources/managing-cystinosis/. Last accessed: December 20, 2019.}

Rare Hematology

Thalassemia is a blood disorder caused by mutations in the HBB gene, resulting in red blood cells that are microcytic and do not contain enough functional hemoglobin.¹ Low levels of hemoglobin lead to a lack of oxygen in many parts of the body.¹

This is an autosomal recessive disease, meaning the parents are carriers of the disease (but are asymptomatic), and the affected individual has two copies of the HBB gene with pathogenic mutations.¹

Because of the low levels of hemoglobin, people with thalassemia also have reduction in the number of healthy red blood cells, resulting in pale skin, weakness, fatigue, and serious complications. Furthermore, some people with thalassemia may need to have their spleen removed, which can increase their risk of developing abnormal blood clots.²

The incidence of symptomatic cases is estimated to be approximately 1 in 100,000 individuals in the general population.³

_{1. Origa R. 2000 Sep 28 [Updated 2018 Jan 25]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1426/. Last accessed: December 20, 2019.}

_{2. Genetics Home Reference. National Institutes of Health. https://ghr.nlm.nih.gov/condition/beta-thalassemia. Last accessed: December 19, 2019.}

_{3. National Organization for Rare Disorders (NORD). https://rarediseases.org/rare-diseases/thalassemia-major/. Last accessed: December 20, 2019.}

Rare Ophthalmology

LHON is the most common inherited mitochondrial (mt) DNA disorder.¹

Over 90% of LHON cases are a result of pathogenic point mutations at mtDNA positions G11778A, G3460A, or T14484C, which code for subunits of the mitochondrial respiratory chain complex I.¹

Overall, approximately 1 in 5 patients will remain within the visual acuity (VA) criteria for legal blindness.

Prevalence of LHON is not well known, but it is estimated at between 1 in 15,000 – 1 in 50,000 people worldwide.¹ The overall male-to-female ratio among patients with LHON averages around 4:1, but this can vary depending on the primary mutation.¹

Adult-onset LHON (15–35 years of age) usually presents as painless, subacute central vision loss in one eye, followed by involvement of the second eye within 1 year in 97% of those affected. In most patients, vision loss is devastating in terms of the impact on their quality of life. Vision loss is permanent.¹

_{1. Carelli V et al. European Ophthalmic Review. 2019;13(Suppl 2). https://www.touchophthalmology.com/lebers-hereditary-optic-neuropathy-a-global-perspective/.}