Cymbalta launched amid renewed controversy
pharmafile | August 26, 2004 | News story | |Â Â Â
Lilly has launched its new depression treatment Cymbalta in the US, a blockbuster tipped to earn $2 billion by 2008.
Cymbalta (duloxetine hydrochloride) is the most important in a string of new product launches at Lilly, but the drug's debut on the market has coincided with the latest development in an investigation into the safety of antidepressant use in children.
Licensed to treat major depressive disorder (MDD) in adults, Lilly claims Cymbalta is unique in its ability to treat both the emotional and physical symptoms of depression, and says clinical studies show only 25-35% of patients treated for depression currently experience relief from all disease symptoms.
As a dual serotonin and norepinephrine reuptake inhibitor (SNRI) Cymbalta differs in its action from SSRIs such as GSK's Seroxat/Paxil – the only other drug in its class, Wyeth's Efexor, is expected to be its main competitor.
Cymbalta's unique dual depression and pain treatment is expected to help sales but analysts predict Lilly will have to battle hard with the well-established Efexor.
Sales of the drug leapt 31% in the second quarter of this year, and it is expected to exceed $3 billion in sales by the end of 2004.
Analysts Datamonitor commented: "Cymbalta has no additional indication for anxiety and lacks clinical data comparing it with Efexor. This may favour Wyeth's drug, as physicians remain reluctant to switch patients to the newer compound without clear evidence of the therapeutic benefits.
"As such, Lilly's own marketing experience, and the collaborations it has entered into with other pharma manufacturers, will be key to maximizing Cymbalta's revenues."
The US launch came just days after the FDA published evidence seemingly confirming an increased risk of suicidality for children using the drugs `- a conclusion similar to that reached by the UK's MHRA at the end of 2003, which then instructed doctors not to prescribe the drugs to children.
Yet, despite strong evidence from the two FDA-commissioned studies, one conducted by its own epidemiologist Dr Andrew Musholder and another blinded study by a panel of international experts for Columbia University, the agency has not indicated it will follow the UK in effectively banning off-label prescribing of the drugs to under-18s.
"While there are findings among these data suggestive of an increased risk of suicidality for some of the drugs, there remains inconsistencies in the results, both across trials for individual drugs and across drugs."
It concluded that an overall interpretation of these findings represented "a substantial challenge".
As with the MHRA investigation in the UK, the US regulator is itself facing serious questions from critics who claim action could have been taken earlier.
The FDA barred Dr Mosholder from presenting his research at a key February public meeting, claiming that further studies were needed to confirm his conclusions. When the findings were later leaked, the FDA was severely criticised for being too secretive.
The controversy has prompted several investigations, including one by the Senate Finance Committee, chaired by Republican Charles Grassley.
"Doctor Mosholder's initial findings have been confirmed and reconfirmed," Grassley said recently in a statement.
"His important work represents the kind of scrutiny the Food and Drug Administration must provide for the public's safety and well-being. When there are known risks with a drug or class of drugs, the information must be made available in a timely way."
Cymbalta's labelling is in line with the new labelling imposed on Efexor and the SSRIs in March this year, which warn patients and their families to watch for thoughts of suicide, and other disturbed behaviour and to call a doctor if any of these symptoms are severe or occur suddenly.
Lilly's Prozac (fluoxetine) is the only drug with a paediatric licence in the US, the FDA clearing its use on the basis of dedicated trials which demonstrated its safety and efficacy.
Despite none of the other drugs having a licence, doctors continue to prescribe them as the incidence of depressive illnesses in under-18s continues to grow.
Lilly was issued with an FDA 'approvable' letter for Cymbalta as far back as September 2002, but the agency required issues relating to its labelling and manufacture to be resolved before final approval.
In a submission to the FDA committee investigating the issue, Lilly quoted one study which estimated 19-22% of children suffer from a major depressive illness, while the WHO forecast that neuropsychiatric problems in minors will rise by over 50% by 2020.
The company articulated the concern that the fear surrounding the drugs could mean some patients are not prescribed the drugs, saying: "It is important that necessary antidepressant treatments are available to all patients who need them, including children and adolescents," adding "information about the safe use of these products is made publicly available."
Lilly announced at the beginning of August that it would publish comprehensive data from all of its marketed drugs to reassure politicians and the public that no significant evidence was being withheld.
This is the charge levelled at GlaxoSmithKline, who are being sued by the New York state attorney Eliot Spitzer, who accuses the company of "repeated and persistent fraud" by withholding data on its drug Paxil.
As a new medicine, Cymbalta will be under close observation for any adverse events in patients, but Lilly is confident of its safety and efficacy profile, presenting data from more than 6,000 adults with MDD as part of its FDA submission.
The drug has not escaped the controversy, however: in February this year, the suicide of a 19-year-old student taking Cymbalta as part of a trial hit the headlines in the US.
Four others diagnosed with depression also committed suicide during trials but Lilly say there is no evidence its drug caused this rather than the underlying condition being treated.
It remains unclear how Cymbalta as a new entrant to the market will be affected by the controversy surrounding antidepressants currently on the market – doctors could switch to it from other drugs, or conversely may be reluctant to start patients on a relatively untested drug against this background.
The drug's active ingredient duloxetine is also being used as a completely separate treatment for stress urinary incontinence known as either Yentreve or Ariclaim in Europe, where it has just been approved through the EMEA.
Related links:
New antidepressant warnings in US and Britain
Thursday , April 01, 2004
