4 min readLife Cycle Management Strategies

Drug development processes consume around $1 billion and 10-15 years from concept to commercialization. Skyrocketing expenditures in pharmaceutical R&D have forced the pharmaceutical industry to invent innovative strategies to maximize their return on investment.

From 2008, a huge number of blockbusters are coming off patent and colossal revenue loss is putting immense pressure on pharmaceutical companies to integrate lifecycle management strategies. Pfizer, Bristol Myer Squibb, Eli Lilly, and others have relied on the block buster business model. On an average, over 40% of their total revenues depend on blockbusters. This business model is not sustainable anymore, as there are practically no innovative molecules in the pipeline. Increasing dependence on patent protection and life cycle management strategies is now the strategy needed at least to sustain short to medium term growth. Dry pipelines have further complicated the issue and pharmaceutical companies are looking for mergers and acquisitions (M&A) or in-licensing to mitigate the effect of patent expiries.

Indication Expansion
Indication expansion is a common strategy employed by most drug companies in order to increase their product longevity in the market or to mitigate the effects of patent expirations. Patents provide market exclusivity for drugs for 20 years and companies have to maximize their return on investment during this patent period. Growing competition, patent challenges, patent infringements and other litigations pose serious threat to the company revenues. However, major revenue loss occurs during patent expirations. Blockbusters feel the pinch of these patent expirations, as almost 50% of their revenues are eroded by generic infiltrations. As competition intensifies, pharmaceutical players rely heavily on innovative life cycle management strategies to stabilize their revenues.

Additional Indications- Monotherapy/Combination Therapy
Drug companies usually research additional indications for which the current marketed drugs can be used. These additional indications can be physiologically related to the primary approved indication or even for unrelated indications. The drug can be extended for use in a combination therapy/monotherapy or as a second line therapy. The move to monotherapy from a combination therapy offers a range of advantages, especially minimal adverse effects, lower drug-drug interactions, improved convenience and patient compliance. The trend of moving from combination therapy to monotherapy has already been witnessed in major drugs, one fitting example being GlaxoSmithKline’s Avandia. This was initially approved for combination therapy with other oral hypoglycaemic agents (OHA’s). However, the company applied for approval as a monotherapy for Type 2 diabetics and this was approved in the EU.

There are instances where the initiatives have been taken to extend the indication to include combination therapy. Merck & Co’s Januvia was approved as a monotherapy, but it was later filed for approval for use as an add-on therapy to a suphonylurea or a combination to suplhonylurea and metformin.

Other Usage extensions
Companies can also expand their market penetration by promoting the use of the drug in maintenance therapy in particular disease areas. In addition, the companies can look into dosing frequency, drug administration with respect to food intake and the like.  There are examples of drugs in the market with these usage extensions, of which Bayer’s Kogenate is one. It was initially approved for bolus infusion, but was extended later to be used for continuous infusion.

Paediatric Extensions
Pharmaceutical companies also look to expand their drugs in the paediatric space as part of their life cycle management strategy. The EU offers extended exclusivity for drugs approved for paediatric indications.

The trend in indication expansion is taking its turn towards complicated indications. The market players are researching expanding the use of their drugs in niche therapeutic areas. This strategy enables companies to not only extend their product lifetimes but also to keep other players at bay.

Company
Drug
Original Indication
Expanded Indication
Abbott Humira Rheumatoid arthritis Inhibiting structural joint damage and improving physical function in PsA
Ankylosing spondylitis
Merck Singulair Asthma Exercise-induced bronchospasm
Ivanz Infections Prophylaxis of surgical site infection
GSK Lamictal Epilepsy Primary Generalized Tonic-Clonic (grand mal) seizures
Relenza Influenza Prevention of influenza
Pfizer Aricept Mild to moderate Alzheimer’s disease Severe Alzheimer’s disease
Celebrex Osteoarthritis pain Juvenile rheumatoid arthritis
J&J Risperdal Depression Irritability associated with autistic
disorder
Remicade Rheumatoid arthritis Ulcerative colitis, Psoriasis, Active ankylosing spondylitis
Levaquin Infections Bacterial sinusitis
Topamax Epileptic seizures Migraines
Table 1-1 lists the drugs with approved indication expansions.
Source: Frost & Sullivan
Strategic planning and well orchestrated clinical programs are essential for a successful indication expansion. Drug developers seek indication expansion for their product even before it is launched. The process is initiated during the Phase III clinical trials. It takes immense planning from the R&D team to initiate indication expansion strategies and to maximize the return on investment. Indication expansions not only enable the company to enjoy a continuous stream of revenues through a new user base, but also help to mitigate the loss incurred due to generic competition. The cost incurred by the pharmaceutical company in expanding indication is estimated to be far less than developing an original product. It is extremely valuable to introduce indication expansion and extend the patent exclusivity for their drugs.

Directed Molecular Evolution (DME)
The market has witnessed the introduction of novel biologics that are likely to face patent expiration soon. The introduction of biosimilars has introduced a major threat to biologics. In addition, the market place for Mab’s is getting crowded. It is expected that by 2010, there will be around 50 Mab’s available. The market is also bound to witness the launch of new biologics, with most of them with similar targets like CD20, CD22, TNF and VEGF. This instigates an urgent need for life cycle management.

Market players could consider adopting the DME technique to meet this need. This involves the use of advanced combinatorial chemistry to research on liable protein candidates that can be used to produce the next generation biologics. It can be used to produce a biologic that has better qualities than its competitors, or it can be utilised to populate its own pipeline with novel biologics that currently not in the market. In another instance, this technique could be used in association with another pharmaceutical company, currently marketing a biologic, to produce the next –generation biologic.

Conclusion
Lifecycle management strategies offer immense benefits to market players due to their ability to extend revenues. However, there are a few limitations associated with these strategies. A major limitation of indication expansion is the likelihood of generic manufacturers introducing the drug without the new indication. One cannot nail the ‘ideal’ strategy and therefore, a complete understanding of the complex interplay of factors is essential.

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