Orphan drug repositioning – to or from a more common disease?

Caroline Mathie

THE PLANNING SHOP international

As we begin our rare disease focus month, Caroline Mathie looks at repositioning of orphan drugs and how this strategy has recently grown across the industry, generating not only clinical development but also business growth.

The benefits of repositioning generally

Finding new uses for known drug compounds is a strategy well recognised by the industry for both clinical development and business growth.

Compounds targeted for repositioning will have already gone through extensive preclinical testing and will have shown safety in their original indication. The key benefits therefore are:-

• Shorter development time

• Lower development costs – safety profiles of the products will have already been established

• Higher success rates

Thompson Reuters estimate that 10% of new molecular entities make it to the market from Phase II clinical trials and 50% from Phase III. The rates for repurposed compounds are 25% and 65%, respectively. They estimate that drug repositioning will have generated US $20 billion in sales during 2012.



Figure 1: A table showing drugs that have been successfully repositioned.

Source: Thompson Reuters

Commercial groups see an opportunity for profits, and non-profit organisations see an efficient way to treat neglected diseases / orphan diseases. Pharmaceutical companies are already making moves either collaboratively or individually to act on these opportunities.


“… 10% of new molecular entities make it to the market from Phase II clinical trials…”


In May 2012, the National Institute of Health (NIH) launched the Therapeutics Discovery pilot program to match researchers with a selection of agents from industry to test ideas for new therapeutic uses. In Fiscal Year 2013, the National Centre for Advancing Translational Sciences (NCATS) will provide up to $20 million for this program. NCATS already has eight collaborators, including Abbott, AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceutical Research &amp, Development, L.L.C., Pfizer and Sanofi. Collectively, these companies have agreed to make 58 compounds available for the pilot program.

Indeed, most large drug companies pursue some sort of drug repurposing activity, either formal or ad hoc. Those that have dedicated resources to repurposing include:

• Novartis: Novartis Institute for Biomedical Sciences – the New Indications Discovery Unit

• Bayer Healthcare: Common Mechanism Research

• Pfizer’s Indications Discovery Unit (IDU)

• Pfizer and Novartis have contracted with Biovista to identify new indications for their drugs

• Roche has a policy to look at multiple indications for its compounds from the outset

In October 2012, AstraZeneca and the Medical Research Council (MRC) announced £7 million of funding for 15 new academic research projects to benefit patients. AstraZeneca has made 22 of its chemical compounds available free-of-charge to researchers who were encouraged to apply for MRC funding to use them in medical research.


“Any potential candidate for repositioning will still have to navigate the regulatory requirements…”


Any potential candidate for repositioning will still have to navigate the regulatory requirements and the extent of the existing data that can be reused will depend upon the extent of change in a drug, its intended new use, its formulation and who holds rights to the intellectual property of pre-existing data.

So, repositioning to or from an orphan disease?

Although there are an estimated 7,000 orphan or rare diseases, only about 350 therapies to treat them are approved. Still, orphan drugs were a $50 billion market in 2011. Orphan drugs can move through approval quickly, bring high prices, and enjoy 7-10 years of market exclusivity by law.

Drugs designed to address a specific genetic deficit or replace a missing enzyme or protein, including all of the enzyme replacement therapies for a range of lysosomal storage disorders, have little potential for true repurposing, but may be repositioned to embrace variants of the original disease as they are identified.

However, the identification of common mechanism of action that allow repositioning from one indication to another are attractive, as seen across oncological indications (e.g. Sutent, which has broadened its indications from the orphan disease renal cell carcinoma and Gleevec, which was designed to be very specific for CML and has since broadened its indications to include other orphan diseases e.g. GIST).

Boehringer Ingelheim has recently invested in ArmaGen Technologies because of the company’s platform that will allow treatments for lysosomal storage disorders with a CNS component to cross the blood blain barrier (BBB). Investing in this technology will give them the patent for this approach, which in time may be expanded for other treatments that need to cross the BBB, including new developments for stroke.

The high cost often associated with R&amp,D orphan disease treatments can be recouped by high prices during their periods of exclusivity.


“Although there are an estimated 7,000 orphan or rare diseases, only about 350 therapies to treat them are approved.”


In contrast however, a product that moves from a common to an orphan disease may incur lower production costs, but find it difficult to recoup the costs of the efficacy trials in the new indication, due to the set prices of the original brand. There is real potential for physicians to use modified doses of the original brand (or the generic when available) instead of the newly developed orphan disease brand. The most noteworthy example is Pfizer’s Viagra (sildenafil), which was repositioned for pulmonary arterial hypertension as Refacto. Others include:

• everolimus – originally an immunosuppressant used following transplant and expanded into rare cancers

• aztreonam – antibiotic for Gram negative infections reposition in an inhaled formulation for patients with cystic fibrosis

The jury is still out on the financial benefits of repositioning into orphan disease indications to extend the protected life of a molecule. There are very clear gains to be made from fast tracking using the orphan drug system as an early high cost entry point for an NCE that can later be extended into broader indications. Either way it is the patients that will benefit.

As market researchers we treat the orphan disease market as a very separate analysis from the broad indication markets for the same drug. Maybe we are underplaying our experience in observing common challenges and solutions when repositioning. Possibly we should think of this and the accompanying methodologies as useful skills in their own right.

About the author:

Caroline Mathie is the Head of the Orphan Disease Specialist Research Group at THE PLANNING SHOP international (TPSi) – a market research-based brand consultancy.

After studying Medical Bio-chemistry, Caroline spent 14 years at IMS Health, over 10 years as an independent Director-level Consultant and 4 years as a Director at J &amp, D Associates.

Throughout her career, Caroline has had an active interest in orphan diseases. This has led her to develop expertise in a wide range of orphan disease conditions, including various lysosomal storage disorders.

In 2010, Caroline joined TPSi as Lead Research Director and Head of Orphan Diseases Specialist Research Group.

You can contact Caroline on +44 (0)20 8231 6888 or at caroline.mathie@planningshopintl.com

How beneficial is it to reposition a drug from a common disease to a rare disease?