Why Developing Cures for Rare Disease Isn’t So Rare Anymore

These Six Maryland Biotech Companies Are Seeing Success in Targeting Rare Diseases

September 3, 2019

Groundbreaking technology and scientific advancements, including cell and gene therapy, have fundamentally changed the way life science companies see rare disease drug development.  

Life science giants like Pfizer, Merck and a host of others—who have traditionally sought big, blockbuster drug approvals—continue to add rare diseases to their drug development portfolios. While oncology and other disease areas with blockbuster potential remain key targets for many bioscience companies, more and more companies see the value—in both patient benefit and economic upside—to investing in new potential treatments and cures for rare diseases.

Biohealth Capital Region (BHCR) companies like Viela Bio, American Gene Technologies, REGENXBIO, Asklepion Pharmaceuticals, Elixirgen Therapeutics Inc., and Cerecor, all featured below, are seeing the value in rare disease drug development investments and now stand at the forefront of this ongoing drug development sea change.

The paradigm shift began in 1983 when the Orphan Drug Act (ODA) became law. The ODA changed everything. 

The ODA enabled biotech companies to finally make a business case for targeting rare diseases because of the new incentives it provided, including tax credits, regulatory approval acceleration, fee waivers and seven years of market exclusivity for drugs that met its criteria. 

In the decade prior to the ODA, only 10 industry supported orphan drugs were brought to market. Since then, 770 treatments have been approved by the U.S. Food and Drug Administration (FDA) and today there are approximately 800 rare disease-focused clinical development projects in process. 

In the U.S. an Orphan Disease is defined as one that affects fewer than 200,000 people; the European Union (EU) defines an Orphan Disease as one that affects less than 2,000 people. Different countries define rare diseases differently, but the reality remains: one in ten Americans suffer from a rare disease and only 5% have FDA approved treatments. The global numbers are a bit murkier, but the World Health Organization (WHO) estimates that perhaps 400 million people worldwide suffer from a rare disease. 

“A patient population outnumbering the combined total of cancer and HIV/Aids patients and equaling that of diabetes, rare disease patients face a unique benefit. The study of rare diseases has been proven to lead to medical science advancements for common illnesses. On the flip side, however, zero of the 7,000 conditions recognized as rare have a cure and a new condition is discovered every other day. It’s not rare to be rare,” stated Lydia Seiders, an independent global strategic advisor for the rare disease community and volunteer state ambassador for the National Organization for Rare Disorders’ (NORD) Maryland Rare Action Network. 

“With Maryland already housing the largest number of Centers of Excellence for the rare disease community, the world travels to us. Roughly speaking, 50% of rare patients are children who will never see their tenth birthday and we need this number to change. Currently, Maryland is on the radar to be the next top biotech state and as a mother of two rare disease patients, there is zero time to wait,” she added.  

When put in that perspective, the label “rare” doesn’t quite seem to fit anymore.    

The Business Case for Rare Disease Investment

So what’s changed so dramatically? Patient populations remain tiny, the cost to patients remains high for approved treatments and the intractable, “untreatable” nature of some rare disorders is still daunting.

Genetic sequencing advancements, increased genetic testing, Big Data analysis and the remarkable evolution of cell and gene therapy technology have all changed the rare disease landscape—just like the ODA did in 1983.

“It’s a whole new world of drug development that is really amenable to these small patient populations and particularly to genetic defects we can pinpoint through more and more data coming from this incredible testing industry evolving around genetics and diagnostics,” stated Jeff Galvin, CEO of American Gene Technologies located in Rockville, Maryland.

“Big data and AI are putting us in a situation where nothing ever gets thrown away,” added Galvin. “Whatever you sequence is going into a database that can be shared all over the world… Now we have this amazing data set to mine for opportunities or for data that would reveal the drivers of a lot of these orphan diseases over time.”

Gene therapy is the altering of a patient’s genetic code to treat or cure a given disease. Cell therapy, on the other hand, generally means the transfer of live, intact cells into a patient (blood transfusions and stem cells, for example), to help alleviate disease symptoms or to provide a cure. These are obvious simplifications of incredibly complex processes, but the bottom line is that cell and gene therapies—in addition to other advancements in small molecule and biologic drug development—have empowered scientists and drug developers to make the science and business case for the investment in rare disease drug development.

Cell and gene therapy, specifically, potentially have shorter drug development timelines, eliminate the need for, and cost of, palliative care and often are delivered in single doses that have lifetime impact. What’s more, small patient populations help reduce marketing and distribution costs. While the price tag might seem astronomical without context, prices will come down over time and the hefty initial price tag, when prorated across decades (given it will often be a one time dose), the initial sticker shock becomes more palatable.

ODA incentives paired with the astounding advancements in science and Big Data have made the treatment of Orphan Diseases less risky and potentially more profitable. The biopharma industry has come to see rare disease drug development as the perfect confluence of increased profitability, reduced costs and the potential alleviation of tremendous patient suffering. 

The BHCR is rapidly becoming a global hub for rare disease drug development. A host of BHCR companies, including many cell and gene therapy companies, have made rare disease drug development a key component of their pipeline strategies. 

Let’s take a look at some of the leading BHCR companies with rare disease treatments within their drug development investment portfolios.    

Viela Bio, Inc., Gaithersburg, MD

Viela Bio’s pipeline is focused on the development of novel treatments for severe inflammation and autoimmune diseases. Their lead drug candidate, Inebilizumab (phase 3 complete), is a monoclonal antibody (MaB) that is a potential treatment for an autoimmune disease called Neuromyelitis Optica Spectrum Disorder (NMOSD). NMOSD is a designated rare disease where the immune system cells and autoantibodies attack the optic nerve and spinal cord, often resulting in blindness, paraplegia, sensory loss, bladder dysfunction, and peripheral pain. 

Leading with a rare disease drug candidate has not scared off the FDA or investors. The company received orphan drug and breakthrough drug status’ from the FDA, and has, since its launch in February 2018, raised in approximately $350M in capital from a host of large investors. The company also just announced plans to go public and raise another $150 Million through IPO later this year.

In March 2019 Viela Bio announced a collaboration with Hansoh Pharma, which will be responsible for leading the development and commercialization of inebilizumab in China. The deal provided Viela with a collaboration fee, milestone payments of more than $220 million, royalties on product sales and a strong partner to support the company’s future global product expansion and lifecycle plans.

American Gene Technologies (AGT), Rockville, MD

American Gene Technologies is a cell and gene therapy company that utilizes a proprietary lentiviral platform to develop potential treatments for liver cancer, Phenylketonuria (PKU), HIV and inherited genetic disorders. AGT’s novel lentiviral platform has enabled the company to develop, test and bank thousands of lentiviral vectors, which can then be matched to develop treatments for new target diseases, including orphan/rare diseases like PKU as well as diseases with larger patient populations.

PKU is an inherited, monogenetic disease that causes excess accumulation of the amino acid phenylalanine (Phe), which can reach toxic levels in the blood without strict dietary control. Children born with PKU (PKU occurs in approximately 1 in every 13,500 births in the U.S.) can suffer brain and organ defects if not placed on a special diet and adults can suffer neuropsychiatric impairments including poor behavioral restraint and limited executive function with high risk of self-injury.

AGT is committed to curing PKU via its proprietary lentiviral platform. The company received FDA Orphan Drug Designation and is progressing its PKU therapy toward the clinic. The company’s leading treatment candidate is a cure for HIV, which is expected to move into the clinic in 2019.

REGENXBIO, Rockville, MD

REGENXBIO is a leading clinical-stage biotechnology company developing gene therapies for retinal, neurodegenerative and metabolic diseases. The company’s proprietary NAV Platform, which was invented to discover next generation adeno-associated viral (AAV) vectors to propel the discovery of new therapies across a wide range of disease areas, including rare/orphan diseases. REGENXBIO has exclusive rights to more than 100 novel AAV vectors and more than 100 patents and patent applications for AAV vectors worldwide.

REGENXBIO currently has 13 clinical stage products and has 20 partnered programs. It’s leading gene therapy candidate is RGX-314 for the treatment of WET age-related macular degeneration (WET AMD), which is the leading cause of blindness in the U.S. 

The company’s pipeline includes several rare disease candidates: 

• RGX-181 received FDA Rare Pediatric Disease and Orphan Drug Designations as a treatment candidate for late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease, one of the most common forms of Batten disease. 

• RGX-121 is a product candidate for Hunter Syndrome (Mucopolysaccharidosis Type II), which is a rare, X-linked recessive disease that causes developmental delay and development regression in children.

• RGX-111 is REGENXBIO’s product candidate for the treatment of Mucopolysaccharidosis Type I (MPS I), a rare, recessive genetic disease that can cause hydrocephalus, spinal cord compression and cognitive impairment

• RGX-501 is REGENXBIO’s product candidate for the treatment of homozygous familial hypercholesterolemia (HoFH). HoFH is a monogenic disorder caused by abnormalities in the function or expression of the LDLR gene. 

REGENXBIO’s pipeline is representative of the balanced approach many bioscience companies strive for with a focus on rare disease and potential blockbuster treatments (WET AMD). To date, there have been only two AAV viral vector-based gene therapy products ever approved, including Novartis‘ ZOLGENSMA for the treatment of pediatric patients with SMA developed using REGENXBIO AAV technology. REGENXBIO is in rarified air as one of only three companies in the world seeing revenue from commercial gene therapies. 

Cerecor, Inc. (CERC), Rockville, MD

Cerecor, Inc. is a publicly traded biotechnology company focused on developing innovative therapies for Orphan Diseases, neurology and ultra-rare pediatric diseases. Founded in 2011, the company has brought numerous prescription medicines, prescription medical devices and dietary supplement products to the market. 

In 2018 Cerecor acquired Advadel US Holdings, Inc. along with all rights to Avadel’s marketed pediatric products, providing immediate non-dilutive funding to invest in their innovative pipeline while positioning the company to become a leading U.S. pediatric pharmaceutical company. In January 2019 the company announced the relocation of its headquarters to Montgomery County, Maryland and in March it raised $10M through common stock purchase, primarily to support the development of its neurology and pediatric rare disease pipeline.

Its pipeline is robust and includes a host of rare disease treatments in early stage development. It’s leading pediatric treatment is CERC-801, an ultra-pure oral formulation of D-galactose currently in development for the treatment of phosphoglucomutase 1 (PGM1) deficiency, also known as PGM1-CDG, which is an inherited genetic disorder with wide ranging symptoms. Other pediatric rare diseases being targeted by Cerecor include the rare, congenital disorder MPI-CDG; Leukocyte Adhesion Deficiency Type II (LADII), also known as SLC35C1-CDG; and the ultra-rare mitochondrial DNA depletion syndrome (MDS), also known as Deoxyguanosine Kinase (DGUOK) deficiency. 

Cerecor also focuses on therapy development for more well known diseases like Parkinson’s Disease and seizure disorders, rounding out a drug development portfolio that is an intriguing mix of small and large patient population R&D investments. 

Asklepion Pharmaceuticals, Baltimore, MD

Asklepion Pharmaceuticals is a biopharmaceutical company based that is exclusively focused on rare disease therapy development, specifically for rare pediatric diseases without viable treatments. The company has shifted to focus exclusively to pediatric rare disease in recent years. Asklepion was founded in 2006 in an effort to commercialize a 15-year academic program focused on developing cholic acid for inborn errors of bile acid metabolism, which is a rare genetic disorder. 

Its leading therapy candidate is for acute lung Injury induced by cardiopulmonary bypass surgery (CBP), which recently completed Phase III clinical trial enrollment in July 2019. Cardiopulmonary bypass surgery can damage lung tissue and blood vessels, which can lead to significant postoperative problems. Asklepion’s treatment is unique in that it is preventative rather than remedial. By intravenously administering the protein building block L-Citrulline pre-surgery, Asklepion believes that postoperative complications caused by CBP.  The treatment received FDA Orphan Drug Designation in 2017. 

Elixirgen Therapeutics Inc., Baltimore, MD

Founded in 2017, Elixirgen Therapeutics, Inc. is a biotechnology company with a focus on using stem cells to cure disease. The company recently announced that it had raised $4M in Series A funding.    

Specifically, the organization is exploring cures using the ZSCAN4. The company’s lead candidate is EXG-34217, a therapy that uses the ZSCAN4 gene to treat people with telomere shortening diseases such as Dyskeratosis Congenita. Dyskeratosis Congenita is a rare genetic disorder that causes bone marrow failure. The company expects to begin EXG-34217 clinical trials in 2019.

The company’s pipeline also includes other telomere shortening diseases, including the rare genetic disorders Fanconi Anemia and Aplastic Anemia, as well as Myelodysplastic syndromes, which is a rare blood disorder. Elixirgen’s pipeline also includes potential treatments for chromosomal diseases like Down Syndrome, age-related diseases like Alzheimer’s Disease and Muscular Dystrophy. Its pipeline represents this industry-wide shift to a more balanced mix between large and small patient population drug development investment.