Top 5 Rare Disease News of the Week—August 5, 2018

#5: Geographic & Racial Disparities Found in Reported US Amyloidosis Mortality

An observational cohort study published in JAMA Cardiology has revealed geographic disparities in reported amyloidosis mortality in the United States and suggests that the rare disease is underdiagnosed in many areas of the country.

Known to most commonly affect the heart, systemic amyloidosis continues to be underdiagnosed, and if left untreated, cardiac forms of the disease are highly fatal. As the majority of amyloidosis mortality is caused by cardiac involvement, the investigators turned to death certificate data to shed light on the epidemiology of amyloidosis.

For their analysis, which they report to be the largest and most racially diverse epidemiological data on reported US amyloidosis deaths to date, the investigators set out to explore trends in amyloidosis mortality reported in the United States from 1979 to 2015 and identify potential regions of the country where the disease might be under-detected.

#4: Cystic Fibrosis Further Explained by Rare Cell Type Discovery

Read more about geographic and racial disparities found in reported in US amyloidosis mortality.Investigators from the Broad Institute of MIT and Harvard and Massachusetts General Hospital (MGH) have discovered a rare cell type in airway tissue that appears to be a key player in the biology of cystic fibrosis.

The discovery of the cell, Foxi1⁺pulmonary ionocyte, establishes the framework for a new cellular narrative for the rare neurodegenerative disease and offers critical insight into the disease’s underlying genetic basis. By explaining the key role of the rare cell in the disease’s biology, investigators provide further insight that can be used to inform the development of targeted cystic fibrosis therapies.

In an effort to better understand what goes awry in the rare disease’s underlying biological functions, the MIT and MGH teams used single-cell RNA sequencing to analyze tens of thousands of cells from the airway in mouse models, charting the physical locations of cell types and mapping a cellular "atlas" of the tissue.

To monitor the development of cell types from their progenitors in the mouse airway, the team also created a new method referred to as pulse-seq, which combined scRNA-seq with lineage tracing. Through this method, the investigators were able to show that tuft, neuroendocrine, and ionocyte cells are continually and directly replenished by basal progenitor cells. The findings were further validated in human tissue.

#3: PBI-4050 Receives Rare Pediatric Disease Designation for Treatment of Alström Syndrome

Read more about how the Foxi1⁺pulmonary ionocyte cell further explains cystic fibrosis.This morning, the US Food and Drug Administration (FDA) has granted a rare pediatric disease designation to Prometic Life Sciences Inc.’s PBI-4050 for the treatment of patients with Alström syndrome.

"This is the first pediatric designation granted by the FDA to our small molecule drug candidate PBI-4050 and the third overall, following the previous 2 granted for our plasma-derived therapeutics candidates,” said Mr. Pierre Laurin, president and CEO of Prometic, in a recent statement. “This highlights the depth and value of our two drug discovery platforms. We look forward to discussing the potential regulatory approval pathway to bring this innovative therapy to pediatric patients with Alström syndrome during our upcoming meeting with the FDA."

#2: Oral Plasma Kallikrein Inhibitor Significantly Reduces Attacks of Hereditary Angioedema

Read more about the FDA’s rare pediatric designation to PBI-4050 Alström Syndrome.Hereditary angioedema (HAE) can be treated with a new drug called BCX7353, according to a paper published in The New England Journal of Medicine.

HAE can affect just 1 or 2 individuals in a group of 100,000, the investigators said, and it can even be fatal. HAE patients can be plagued by recurrent episodes of severe swelling of the skin and mucous membranes. Typically, HAE appears on the face and around the lips but does not usually leave lasting marks; it can be serious if the swelling occurs in the throat or tongue and blocks the airway, or milder symptoms last more than a few days, according to the Mayo Clinic.

“HAE is a condition that may be associated with lifelong impairment,” principal investigator Emel Aygören-Pürsün, MD, said in a recent statement. Dr Aygören-Pürsün works at the HAE competence center at University Hospital Frankfurt. “With this fundamentally new development, we may reduce HAE attacks and consistently improve our patients' quality of life.”

#1: FDA Approves First Medicine to Treat Underlying Cause of Cystic Fibrosis in Children with Most Common Form of Disease

Read more about how BCX7353 significantly reduces attacks of hereditary angioedema.The US Food and Drug Administration (FDA) has approved lumacaftor/ivacaftor (ORKAMBI) to include use in children ages 2 through 5 years with cystic fibrosis who have 2 copies of the F508del-CFTR mutation; it is the first medicine approved to treat the underlying cause of cystic fibrosis in this population.

“For the first time, children ages 2 through 5 who have the most common form of cystic fibrosis have a treatment for the underlying cause of their disease,” said Reshma Kewalramani, MD, executive vice president and chief medical officer at Vertex, in a recent statement. “We believe it is important to treat the underlying cause of the disease as early as possible and this approval is another significant milestone in our journey to bring effective medicines to all people living with cystic fibrosis.”

The treatment is a combination of lumacaftor—which is designed to increase the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the F508del CFTR protein—and ivacaftor—which is designed to enhance the function of the CFTR protein once it reaches the cell surface. Lumacaftor/ivacaftor oral granules are available in 2 dosage strengths (lumacaftor 100mg/ivacaftor 125mg and lumacaftor 150mg/ivacaftor 188mg) for weight-based dosing and should be available for fulfillment within 2 to 4 weeks.

Read more about the FDA approval of lumacaftor/ivacaftor to include use in children ages 2 through 5 years with cystic fibrosis who have 2 copies of the F508del-CFTR mutation.