Big Pharma and their adoption of Orphan Drug Research

A rare disease/disorder is defined as such when it affects fewer than 200,000 (USA) or fewer than 2000 (Europe) of the population at any given time. To date, over 7000 rare diseases have been identified, affecting more than 350 million people globally. In the EU, as many as 30 million people may be affected, with the same number affected in the USA. Fifty percent of those affected are children, with approximately 52 million of these children not living to see their 5th birthday.1 Considering that only 5% of rare diseases have an FDA approved drug, how much research is being carried out by Pharmaceutical companies towards orphan diseases?

Drug discovery is an expensive and time-consuming business, with strict regulatory standards and high attrition rates. According to the Tufts Center for the Study of Drug Development, as of 2014 the cost of developing a single drug stood at approximately $2.9 billion.2 Traditionally, big Pharma focused on developing drugs aimed at “common diseases” with a large patient population to maximize the possibility of recovering research and development costs, with rare diseases pushed aside because they provided little financial incentive. These rare diseases were said to be “orphaned”, and can also include common diseases that have been ignored because they are far more prevalent in developing countries than in the developed world.

In 1983, Congress passed the Orphan Drug Act which provided manufacturers with three attractive primary incentives.

  • Federal funding of grants and contracts to perform clinical trials of orphan products
  • Tax credit of 50% of clinical testing costs
  • An exclusive right to market the orphan drug for 7 years from the date of marketing approval

The Food and Drug Administration commissioned the Office of Orphan Products Development (OOPD) to dedicate its mission to promoting the development of products that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions. In fulfilling that task, the OOPD interacts with the medical and research communities, professional organizations, academia, governmental agencies, and the pharmaceutical industry, as well as rare disease groups. The OOPD also administers the Orphan Products Grants Program which provides funding for clinical research that tests the safety and efficacy of drugs, biologics, medical devices and medical foods in rare diseases or conditions.3 The program has successfully enabled the development and marketing of more than 400 drugs and biologic products for rare diseases since 1983. In contrast, the decade prior to 1983 saw fewer than ten such products come to market.

So, with this in mind, how has research into orphan drugs progressed?

One biotech company stands out. Genzyme was founded in 1981, producing modified enzymes to test in clinical trials. In 1991, Genzyme won FDA approval for Ceredase for the treatment of Gaucher’s disease, the success of which allowed Genzyme to concentrate research into recombinant human enzymes to treat enzyme deficient conditions. To overcome supply constraints, Cerezyme quickly replaced Ceredase a few years later, and in 2010 Genzyme became the fourth largest American biopharmaceutical company with a revenue of $4 billion. In 2011 Sanofi acquired Genzyme for approximately $20 billion making Genzyme its global center for excellence in rare diseases.

The marriage between Shire and Baxalta early this year has made them the Global leaders in rare diseases, creating the number one rare diseases platform in revenue and pipeline depth.4 The combined portfolio will have over 50 programs that address rare diseases. Shire anticipates more than thirty recent and planned product launches from the combined pipeline, contributing approximately $5 billion in annual revenues by 2020.

Big pharma now wanted a slice of the pie, and drug research into rare diseases was not exclusive to Biotechs.

In 2014 Pfizer joined with the Global Medical Excellence Cluster (GMEC), a group of six leading UK universities to form a Rare Disease Consortium, focusing on exploring the human genome to treat hematologic, neuromuscular and pulmonary rare diseases.5 Professor Michael Linden (Kings College London) joined Pfizers newly formed Genetic Medicine Institute in 2015 to evaluate the viability of producing effective, clinical grade gene therapy viruses.6

In 2015, Dr. Mark Fishman, President of the Novartis Institutes for BioMedical Research (NIBR) stated that “Our focus on rare diseases flows from our desire to help patients underserved by today’s medicines.” Novartis scientists have investigated treatments for more than 40 rare diseases, with the US Food and Drug Administration granting Novartis dozens of “orphan drug” designations. They also have more than 15 medicines approved for these conditions.7

In 2015 Roche bought the French pharma company Trophos and its lead drug for the rare neuromuscular disease spinal muscular atrophy (SMA) for €470 million.8 They have also taken on board the genomics firm Foundation Medicine  as well as a collaboration with genetic testing specialist 23andMe in Parkinson’s disease.9

GSK has established its own research unit exclusively devoted to seeking cures for rare diseases. GSKs partnership with Ospedale San Raffaele Telethon Institute for Gene Therapy and Fondazione Telethon (Telethon) has resulted in a recent European approval for Strimvelis, the first ex-vivo stem cell gene therapy to treat patients with the very rare disease, ADA-SCID.10

In April this year, Astra Zeneca announced that along with MedImmune, a genomics initiative has been launched to transform drug discovery and development across its entire research and development pipeline. AstraZeneca has partnered with research institutions including the Wellcome Trust Sanger Institute (UK), Human Longevity Inc. (US), and The Institute for Molecular Medicine (Finland) in the hope to unearth rare genetic sequences that are associated with disease and with responses to treatment.11

The emergence of patient advocacy groups has improved the understanding of how debilitating these diseases can be, with the non-profit organisation Global Genes® being one of the leading rare disease patient advocacy organizations in the world, promoting the needs of the rare disease community.1 Passing of the FDA’s Orphan Drug Act (and similar legislation in other countries) paved the way for biotech companies to carry out research into rare diseases, offering government incentives, shorter development timelines, and exclusive markets rights. Smaller clinical trials with a reduced patient pool and FDA fast track designation has led to an average time of 3.9 years from Phase II to launch, compared to 5.4 years for non-orphan drugs.12

Research into rare diseases by smaller companies was also made possible through funding by non-profit organisations such as the Cystic Fibrosis Foundation, operating like a venture capital firm. Big Pharma can support expensive research costs, especially when orphan drugs can bring in attractive revenues – Cerezyme has an annual treatment cost of  $300,000 per patient! According to the EvaluatePharma Orphan Drug Report 2015, worldwide sales are forecast at $178 billion by 2020, with the market growing by 11% each year.13

However, with more orphan drugs coming to market and the high costs per patient, will healthcare systems be able to continue to pay/subsidise for them?

Blog written by: Kamlesh Bala



  12. Meekings KN, Williams CSM, and Arrowsmith JE. Orphan drug development: an economically viable strategy for biopharma R&D. Drug Discovery Today 2012; 17 (13/14):660-664.



Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s