Rare Disease Day, which takes place at the end of February, is designed to focus global attention on the need for therapies to treat patients suffering from devastating rare diseases that have, as yet, no effective treatments and limited research and funding to change the situation.

The most recent event represented the eighth year the campaign has been held. Its impact over that span has been impressive in helping to raise interest, awareness and research funding. It can be said that interest and research on rare diseases has never been higher.

According to a new report released by the Pharmaceutical Research and Manufacturers of America (PhRMA), titled "A Decade of Innovation in Rare Diseases," it points to the significant progress that has been made in our understanding on a range of diseases in that area.

The report documents that 230 new medicines to treat rare or "orphan" diseases have been approved by the FDA during the reporting period, and there are more than 450 orphan drugs in development.

Last year, the FDA reported that of the 41 new drugs approved by the Center for Drug Evaluation and Research (CDER) as new molecular entities, approximately 41 percent were targeting rare or orphan diseases. (See Part 2 of this feature.)

"Rare diseases are one of the most scientifically complex health challenges we face," said PhRMA President and CEO John Castellani.

However, progress is being made thanks to our greater understanding of the genetic underpinnings of their causes.

BIG DATA

The emerging field of big data could be the wellspring to launch promising rare disease research. Recent technological improvements to allow processing, aggregation, standardization and security of large datasets that were not yet available for research before is now coming online. Branford, Conn.,-based Bioxcel Corp., for example, is working with industry partners to help improve upon its decision-making in drug discovery. The firm has developed a cloud-based big-data analytics platform, known as PharmGPS, a disease area-focused, analytics engine encompassing all major and specialty therapeutic areas.

The company has introduced an orphan disease suite to aid in the discovery, development, licensing and commercialization of drugs for the approximately 7,000 rare and ultra-rare diseases that have been identified.

The firm's underlying metadata and analytics for the gamut of orphan diseases, its 3,000 associated genes and hundreds of disease pathways related to therapeutic modality, is designed to address that complexity in a highly systematic manner and help partners explore innovative ideas and uncover valuable potential therapeutic approaches. (See BioWorld Insight, Sept. 15, 2014.)

RAMPING RESEARCH

The NIH is funding a research consortia to study more than 200 rare diseases, with awards totaling about $29 million in fiscal year 2014, to expand the Rare Disease Clinical Research Network (RDCRN), led by the NIH's National Center for Advancing Translational Sciences. Physician scientists at 22 consortia will collaborate with representatives of 98 patient advocacy groups to advance clinical research and investigate new treatments for patients with rare diseases.

The network, originally established in 2003, has enabled a number of translational research successes to date, including advances at the Urea Cycle Disorders Consortium at Children's National Medical Center in Washington. Patients with urea cycles disorders have a severe deficiency or are missing one or more of the first four enzymes in the urea cycle. With the new awards, scientists at the 22 RDCRN consortia will conduct a minimum of two multisite clinical studies, including one longitudinal natural history study for a group of at least three related rare diseases. (See BioWorld Today, Oct. 9, 2014.)

Research at the NIH also is being translated into therapies. NIH researchers entered an agreement with Vtesse Inc., of Gaithersburg, Md., to develop treatments for Niemann-Pick disease type C (NPC) and other lysosomal storage disorders. (See BioWorld Today, Jan. 8, 2015.)

Lysosomal storage diseases, also known as lipid storage diseases, comprise about 50 rare inherited disorders that usually affect children. Fatty materials accumulate in the cells and tissues of the body. Those diseases can result in damage to the brain, peripheral nervous system, liver, and other organs and tissues; they are often fatal.

Vtesse will support the ongoing phase I trial for NPC at the NIH Clinical Center, led by National Institute of Child Health and Human Development (NICHD) researchers who have been evaluating the safety of the drug cyclodextrin. Vtesse also plans to collaborate with NICHD to launch a second clinical study of cyclodextrin for the treatment of NPC in the U.S. and Europe.

Another project that has made its way into clinical development is targeting autosomal dominant retinitis pigmentosa, a rare genetic disease of the eye, characterized by the loss of the light-sensing cells of the retina. Researchers found the most common genes involved in the condition have changes in the protein opsin. Lead collaborator for that project, Bikam Pharmaceuticals Inc., identified and began developing compounds that correct abnormal forms of opsin.

In July 2014, Shire plc reported that it completed the acquisition of Bikam, paying on closing $2.5 million. According to the 10-Q filing, further payments of up to $92 million may be payable upon the achievement of certain development, regulatory and sales milestones.

Editor's note: Part 2 of this feature will appear in next week's issue.