Event - Lilly looks to Cymbalta expansion

Expert advisers to the FDA will at long last hear the case to add chronic pain to the list of indications for Cymbalta on August 19. A recommendation for approval would be a modest positive for Eli Lilly as the Indiana firm faces up to its patent cliff woes.

Analysts from Jefferies estimate the chronic pain indication will add $500m in revenue before the antidepressant loses patent protection in 2013; 2009 sales reached $3.08bn worldwide. Regardless of the views of the FDA Anaesthetic and Life Support Drugs Advisory Committee, however, it is thought the product is already seeing off-label use following a recommendation by a US anaesthetics society that SNRIs like Cymbalta be used to treat chronic pain. Still, with Lilly in desperate need of growth drivers, a positive vote would go down well.

Product Cymbalta
Company Eli Lilly
Market cap $43.6bn
Product NPV $5.44bn
% of market cap 12%
Event type FDA advisory committee
Date August 19, 2010

Whilst the increased revenue from the line extension will be modest, it will also be welcome as Lilly’s patent cliff issues are amongst the most significant in the industry. Between now and the end of 2014, five products with a combined net present value of $21.3bn will lose patent protection – compared with an overall company NPV of $59.6bn. Meanwhile the combined NPV of its phase III assets, all projected to launch by the end of 2014, is $5.4bn, according to EvaluatePharma's NPV Analyzer.

Approval pains

Cymbalta, known generically as duloxetine hydrochloride, has been approved since 2004 for depression and has undergone an expansion of indications to include fibromyalgia, generalised anxiety disorder and diabetic peripheral neuropathic pain. Its effects in mental health indications relate to the activity of serotonin and norepinephrine in the brain and spinal cord, which may also affect the perceptions of pain.

Its path toward approval in chronic pain has not been exactly straightforward for an already-approved drug; Lilly submitted and then withdrew an application in 2008 after FDA staff questioned the design of pivotal studies – one of which failed in its primary endpoint in chronic low back pain - a poor harbinger for a candidate in the increasingly difficult pain indication.

Lilly resubmitted in June 2009, but continuing a string of poor indicators an advisory committee meeting scheduled in January was cancelled.

Despite these harbingers, compared with other classes of pain-relieving drugs Cymbalta has a relatively benign safety profile, and is a known quantity given its use in fibromyalgia and diabetes-related pain.

The black-box warning it has on suicide risk deals with children and it is not licensed for paediatric use. It is without doubt, however, that the overwhelming majority of chronic pain patients are adults. Thus, efficacy will be the main question being considered by the expert panel.

Reducing knee and back pain

The application will rest on data in osteoarthritis-related knee pain and chronic lower back pain in addition to fibromyalgia and diabetic pain data. A recent knee study pitted 60mg-120mg daily doses of Cymbalta against placebo over 13-weeks. Of the Cymbalta patients, 65% saw a clinically significant reduction of at least 30% in their 24-hour average scores in the brief pain inventory (BPI), compared with 44% of patients in the placebo arm – a significant difference.

A recent 401-patient low back pain study compared 60mg daily doses of Cymbalta against placebo over 12 weeks and also found a statistically greater improvement on the BPI scale in the Cymbalta treated group, although 30 Cymbalta-treated patients withdrew because of adverse events compared with 11 in the placebo group.

No company, not even a pharma giant like Lilly, is likely to turn its back over an extra $500m in revenue. However, a new indication for its second-best-selling drug will not solve Lilly's problems, but it will help.

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