Shire Pharmaceuticals is the global market leader in the sale of attention deficit drugs with the products Adderall, an instant-release amphetamine introduced in 1996, and Adderall XL, a timed-release version of the drug, introduced in 2001.
Adderall and Adderal XL are the top selling attention deficit treatments in the US. In 2004, Shire captured 28% of the US market and according to Bloomberg News on February 10, 2005, Shire sold about $759 million worth of Adderall XR in the US and roughly $10 million in Canada.
The drug contributed about half of the firm's $1.3bn (£695m) annual sales total, according to the February 11, 2005 Guardian.
For the past year, Shire has been a continuous rollercoaster ride. The company took a major tumble in February 2005, when Canadian health authorities pulled Adderall off the market due to reports of 20 sudden heart-related deaths and strokes in children and adults using the extended-release pill.
Fourteen of the deaths were children and two of the 12 strokes were in children. The adverse events were reportedly not associated with drug overdose or misuse of the drug.
The Canadian news release said the incidence of serious reactions leading to death were higher with Adderall and Adderall XR combined, than with any other medications in the same class of drugs.
In immediate response to the action, the Guardian reported a 10% fall in Shire Pharmaceuticals' share price.
Instead of investigating the matter at the time, the FDA merely posted an alert on its website that said Health Canada has suspended marketing of Adderall XR products due to concern about reports of sudden unexplained deaths and issued an advisory to healthcare professionals that the Canadian regulatory agency had suspended the sale of the drug.
However, not only did the FDA not investigate, an agency employee reportedly tried to talk Canadian officials out of banning Adderall, in an attempt to deflect FDA involvement in another drug-safety related controversy. Congressional committees were already grilling the FDA on its failure to reveal safety problems with other classes of top selling drugs.
Shire appealed the decision to remove its product from the market to Health Canada, and a panel of experts was convened to determine whether Adderall was more dangerous than other attention deficit drugs sold in Canada.
Seven months later, in August 2005, Health Canada reinstated approval for Adderall based on a finding by the New Drug Committee that the product could not be conclusively associated with the increase in the cardiovascular events and deaths.
According to the October 11, 2005 Canadian Medical Association Journal, health officials voted to reintroduced the drug not because the agency found it safe, but because "an independent panel found it impossible to accurately ascertain whether the drug increases the risk of cardiac death."
The committee in fact evaded the underlying safety determination. Committee Chairman, Dr Mitchell Levine, said it was impossible to prove or disprove that Adderall increased the risks of sudden cardiac death or stroke, and when compared to similar drugs, it was also impossible to determine whether Adderall "was particularly worse or more harmful."
The New Drug Committee did find that it is "biologically plausible" that there is an increased risk with any stimulant drug, but due to the uncertainty of whether Adderall was more dangerous than others, the panel recommended that it be returned to the market with a revised warning label.
The new package insert included warnings about the misuse of Adderall and said that Adderall generally should not be used in patients with structural cardiac abnormalities.
The good news in Canada brought no time for a breather, because another problem was on the horizon for Shire in the fall of 2005. Impending generic competition was threatening to knock Adderall off its top shelve pedestal in the market.
Shire quickly took legal action to defend its number one position by asking US regulators to impose more testing on generic versions of the drug and filed law suits against Barr Laboratories and Impax Laboratores for patent infringement.
The company also filed a Citizen Petition with the FDA, to require competitors to show that their products were equally effective in treating patients, before allowing them to be sold, to delay approval through more testing.
However, even with these legal bases covered, Shire's worries were far from over. At the start of the new year, the next round of headaches arrived, when the FDA finally awoke from its usual and customary position of being asleep at the wheel when it comes to warning citizens about potential harm from lethal products of the pharmaceutical industry.
On January 6, 2006, Medical News Today, reported that the FDA had asked its Drug Safety and Risk Management advisory committee to examine ways of studying the potential cardiovascular risks of attention deficit drugs in response to reports of deaths and other serious adverse events in persons who had taken the medications.
According the FDA web site: "Cases of sudden death and serious adverse events including hypertension, myocardial infarction, and stroke have been reported to the agency in association with therapeutic doses of drugs used to treat Attention Deficit Hyperactivity Disorder (ADHD) in both pediatric and adult populations."
"The few controlled clinical studies of longer term drug treatment of ADHD provided little information on cardiovascular risks," it said.
The agency's web site does not specifically identify any drug by name but it's no secret that Adderall is the most commonly prescribed attention deficit drug in the US.
That said, Shire is definitely not the only company worrying about the FDA investigation. The financial stakes are high for every attention deficit drug maker. Billions of dollars in sales are hanging in the balance.
According to the market research firm IMS Health, overall spending on attention deficit drugs has increased from about $750 million in 2000 to over $3 billion in 2004.
Prescriptions for these drugs are on the rise for people in every age group. On September 15, 2005 the Associated Press reported that the use of drugs for attention deficit hyperactivity disorder is growing at a faster rate among adults than children.
Nearly 1.5 million Americans over 20 years old are using the drugs, according to Medco Health Solutions, the nation's largest prescription benefit manager. Between 2000 and 2004, the use of these drugs has doubled among adults ages 20 to 44, and has increased 56% among children, Medco reports.
However, the most shocking increase in the use of attention deficit drugs is with toddlers. From 2000 to 2003, prescriptions for children under 5 contributed to an overall 23% increase for all children, according to an annual analysis by Medco.
And last but not least, not surprisingly, Adderall is becoming the recreational drug of choice for high school and college students. In a July 2005, Student Drug Research Survey of University of Maryland college students by the Maryland Drug Early Warning System, Adderall was listed as the third-easiest drug to get at the University after alcohol and marijuana.
On January 23, 2006, the Fond Du Lac, Wisconsin school board voted to expel students involved in selling and trading Adderall. Eleven students in all were suspended for their part in distributing the drug.
School authorities referred the students to prosecutors after arresting them last month. Police say a 14-year-old female student stole the drug from her three siblings to whom it had been prescribed. She took some of the pills herself and sold some to classmates.
As of January 19, 2006, Shire was back at the top of the rollercoaster again after it settled its legal battle with generic rival Impax. Once Shire confirmed the deal, company stock rose 8%.
READ MORE Adderall LEGAL NEWS
Although Shire is said to be involved in settlement discussions with Barr Laboratories, analysts agree that any potential agreement with Barr is unlikely to be so favorable.
Because the system of reporting adverse events is voluntary, analysts say that the events reported on any given product represent only 1-10 percent of the actual number of adverse reactions. In other words, there may have been thousands of deaths in people on Adderall.
So the question remains, how many more reports of deaths and serious injuries have to surface before regulatory officials protect potential victims by pulling Adderall off the market.