Off-Label Ltd

WWW .OFF-LABEL.COM – a low cost/low risk R&D strategy

The biopharmaceutical industry has a problem: output has not kept pace with the enormous increases in Pharma R&D spending. This gap in productivity exists despite the enormous amounts invested in novel discovery technologies that include structure-based drug design, combinatorial chemistry, high-throughput screening and genomics. Four years ago widespread hope for a new era in the prevention and treatment of disease was the promise implicit in the sequencing of the human genome. But as the FDA recently emphasised [‘Innovation or Stagnation? Challenge and Opportunity on the Critical Path to New Medical Products’ FDA March 2004], that new era has not yet arrived. In the US the number of new drugs approved by the FDA has declined steadily from more than 50 drugs per annum 10 years ago to less than 20 drugs in 2002. Alarmingly, this trend has persisted even though the industry has witnessed an unprecedented scale of mergers and acquisitions together with annual R&D expenditures of approximately US $30 billion [EMBO reports 2004 5 1016].

For many drugmakers generic erosion is substantial. With 79.7% of 2003 blockbuster sales potentially exposed to generic competition by 2010, equating to US $103.7 billion worth of products at 2003 sales value, the growth opportunities in the generics sector are significant [Datamonitor, 2005]. However, as the operating environment for generics becomes increasingly competitive effective portfolio management together with low cost supply by themselves are not enough to ensure survival. As the differences between branded and generics companies becomes increasingly blurred, sustainable growth will only be achieved through continuous innovation in exploiting the sea of unmet clinical needs that remain following picking of the blockbuster ‘low-hanging fruit’ diseases, such as hypertension or hypercholesterolaemia.

Specialty Pharma – new uses for existing drugs

The process of finding new uses outside the scope of the original medical indication for existing drugs is an area of Specialty Pharma that is growing steadily. With this approach, development risk is reduced because candidate drugs will have passed through several stages of clinical development and therefore have well-known safety and pharmacokinetic profiles. Shorter routes to the clinic are also possible because in vitro and in vivo screening, chemical optimization, toxicology, bulk manufacturing, formulation development and postmarketing surveillance will in many cases have been completed. Together these factors enable several years, substantial risks and costs to be removed from the pathway to the new market. Consequently, ‘repositioning’ of existing drugs can offer a better risk-to-reward ratio by comparison with other drug development strategies.

Both blessings and unique challenges surround IP issues associated with repositioning. On the plus side, new IP in the repositioned indication can create substantial value for the repositioner. However, since the candidate drug is usually not new to the scientific community, prior art might exist that at a first glance can render a repositioning prospect as unpatentable. Such is the case of course for repositioning off-patent drugs through commercialization of an unlicensed (ie off-label) use when such use has previously been reported and made known within the public domain (ie published).

Looking again at the plus side the extent and diversity of off-label use is considerable and invariably represent attempts by clinicians to fulfil unmet needs. Consequently, in commercial terms these findings represent an invaluable R&D resource. Each month 400 new reports of off-label use are added to www.off-label.com. For the first time this extensive R&D resource has been systematically incorporated within an easily accessible library. Www.off-label.com is however much more than just a library. Www.off-label.com was developed by McCormack Ltd, a company with 21 years experience in extending product life-cycles through the creation of novel IP.

www.off-label.com is in two parts

The first part is the search facility. Subscribers can search for new market opportunities across over 300 therapeutic subcategories contained within 21 therapy sections. This library is updated and kept current on a daily basis. The second part provides access to experts who will evaluate client-selected off-label uses and recommend strategies for creating barriers to entry that effectively surmount the existing prior art. This second part is available as a separately-charged service.

The following sections look at ways in which the Off-Label database can be used together with insights into what the Consultancy service can offer.

Using www.off-label.com

The core database  

• To search by drug or condition, use the toolbar on the left of the page ‘Searching the UK (US) database’. For more advanced searching enter search criteria into some or all of the boxes provided.
• By entering a company name entries will be filtered according to individual manufacturer.
• If your search for commercialization candidates is not restricted to a particular drug or disease, then the database has been designed for rapid searching.
• For categories with less than 500 entries (eg Eye), type the category name into the box ‘Off-label therapeutic category’ on the search page, click ‘Submit’ and then scroll down the entries. For large categories with more than 500 entries (eg Malignant Disorders), click onto the chosen category using the toolbar on the left of the search page, and then search by individual subcategories (eg Bone, Cervix). Remember, new entries are added daily.
• If you wish to view off-label citations in which the selected drug was used at a dose or frequency of dosing outside of that described within the marketing authorization/label then enter the drug name into the box ‘Drug generic name’ on the search page. Next type in either ‘low dose’ ‘high dose’ ‘low frequency’ or ‘high frequency’ (only one phrase at a time) into the box ‘Key word or phrase…’ and then click ‘Submit’. Alternatively, you can search by dose or dosing within each category. In this case type the category name (eg Skin) into box ‘Off-Label Therapeutic Category’.
• To identify off-label citations according to routes of administration enter the drug name into the box ‘Drug generic name’ and/or enter the category name (eg Skin) into the box ‘Off-label therapeutic category’. Enter a route with the prefix 'Intra' (eg Intraarterial) into the box ‘Key word or phrase…’ do not use a hyphen. Click ‘Submit’.
• Many off-label uses, and most if not all of the first-time uses will not be detected by traditional methods of prescription event monitoring. Consequently, www.off-label.com is an invaluable forecasting aid when assessing future sales of any licensed drug. Used in this way www.off-label.com will help generics manufacturers for example, to maintain maximal revenue from a carefully-selected portfolio.

Pharma & Biotech Members Area

UK (US) First Use Area

 Entry to the First-Use Area is via the www.off-label.com home page. Available under a separate subscription entries within this area represent details of novel off-label observations limited to the published findings of a single group (indexed on Medline). Consequently, selections from this area will almost certainly provide a ‘head start’ to market.

UK (US) Combinatorial Library

Entry to the Combinatorial Library is via the www.off-label.com home page. Available under a separate subscription the Combinatorial Library provides details of published reports of www.off-label.com uses that involve an admixture or sequential administration of different drugs. Synergies, where they exist, frequently represent increased efficacy in areas of high unmet needs (eg neuropathic pain) and usually with fewer side effects.