In February 2000, Anita Smith, a 46-year-old wife and mother of two, was diagnosed with multiple sclerosis (MS). By April 2002, she was enrolled in a clinical trial involving the MS drug, Tysabri along with 1,200 other patients.
In November 2004, while Anita Smith’s health was rapidly deteriorating and she was experiencing severe neurological problems, Tysabri gained a coveted “fast-track” approval from the FDA.
Anita Smith took her last IV infusion of Tysabri in January 2005. On February 24, 2005 she died of a rare, and often fatal, brain infection known as PML; a disease that has struck at least four other Tysabri patients (killing one).
Four days later, Tysabri sales were halted. Coincidence? Not according to respected scientists and other experts who had warned of such potential consequences associated with the powerful immunosuppressant and certainly not according to attorneys for the Smith family who, yesterday, filed a wrongful death lawsuit against Tysabri’s manufacturers.
A review of the extensive 64-page (315-paragraph) complaint with 14 separate causes of action reveals the following facts and allegations:
Tysabri is the product of a partnership between Biogen Idec Inc. (Biogen), a Delaware corporation with its principal place of business in Massachusetts, and Elan Corp. PLC (Elan), an Irish corporation that does business within the state of Massachusetts.
Tysabri, originally known as Antegren, is an immunosuppressant intended for the treatment of MS.
A second MS drug, Avonex, is also manufactured by Biogen and was used jointly with Tysabri as an MS treatment during clinical trials.
In April of 2002, Anita Smith was enrolled in a clinical trial of Tysabri.
Anita Smith’s neurologist was already treating her with Avonex since February 2000.
Anita Smith’s neurologist was paid (as an agent, servant, or employee) by Biogen and Elan as an “Investigator” in their clinical trial of Tysabri.
Biogen and Elan told Anita Smith that Tysabri was reasonable safe and effective. She was given “no information that the use of Tysabri could lead to opportunistic infections being transmitted to the brain.”
While taking Tysabri and Avonex in the clinical trial, Anita Smith and others developed opportunistic infections including Progressive Multifocal Leukoencephalopathy (“PML”).
PML is a typically fatal brain disease caused by the immunosuppressive effects of Tysabri or the immunosuppressive effects of Tysabri in combination with Avonex.
In February 2000, Anita Smith was diagnosed with MS.
In April 2002, some 1,200 subjects (including Anita Smith) became part of a clinical trial of Tysabri.
Anita Smith was never given any specific tests or studies to confirm her eligibility to participate in the subject clinical trial although the defendants had an opportunity to request and could have requested additional tests and studies be performed in order to evaluate her eligibility and/or suitability to participate in the subject clinical trial.
The defendants should not have enrolled Mrs. Smith in the subject clinical trial in the presence of her improved symptoms to the point of resolution or near resolution.
Anita Smith was never warned of the immunosuppressive qualities of Tysabri or Avonex.
Anita Smith was never warned of the significant risk of developing opportunistic infections like PML.
Anita Smith was never warned that death was a risk of treatment with Tysabri.
Her treatment was comprised of 30 IV infusions beginning on April 12, 2002 and ending in January 2005.
Tysabri received fast-track FDA approval in November 2004.
Anita Smith’s health began to deteriorate and she started suffering severe neurological problems in November 2004.
Anita Smith was hospitalized on February 12, 2005 and was diagnosed with PML.
Anita Smith died on February 24, 2005.
Tysabri sales were suspended by defendants on February 28, 2005.
An autopsy (participated in by defendants) confirmed that Anita Smith died of PML.
An explanation of the mechanism of the infection is set forth in detail as follows: On March 2, 2005, Forbes published an article about PML under the headline, “The Virus That Took Down Tysabri,” which described the virus’s latent virulence as follows:
The JC virus, discovered in 1971 and named with the initials of the patient in whom it was found, is present in almost everyone but only destroys the brain when somethings damages the immune system and allows the virus to run rampant.”
In 1992, based on animal studies and other in vitro experiments, scientists who developed Tysabri concluded that it was far too dangerous to use in humans.
Tysabri acts on MS by suppressing the immune system.
PML is a typically fatal infection.
PML results from suppression of the immune system.
Individuals who take Tysabri become susceptible to PML because Tysabri suppresses the immune system.
Individuals who take Tysabri in combination with Avonex become susceptible to PML because Tysabri suppresses the immune system.
By suppressing the immune system, Tysabri allows the JC virus, ordinarily latent in a patient’s kidney, to travel to the brain via the bloodstream, where it begins uncontrolled replication.
By suppressing the immune system, Tysabri taken in combination with Avonex allows the JC virus, ordinarily latent in a patient’s kidney, to travel to the brain via the bloodstream, where it begins uncontrolled replication.
Like Tysabri, Avonex is also an immunosuppressive agent.
When taken in combination with one another, Avonex and Tysabri result in a substantial increase in immunosupression or reduced immune surveillance.
When taken as a combination therapy, Avonex and Tysabri result in increased immunosupression, or an increased reduction in immunosurveillance, greater than that which would have occurred if either of the two drugs were taken in mono-therapy.
The combined use of Avonex and Tysabri has synergistic effects which result in supression of the immune system.
The combined use of Avonex and Tysabri has synergistic effects which result in increased supression of the immune system over that which would have been realized if either of the two drugs were taken in mono-therapy.
Defendants knew that after administration of the combination therapy for 20 weeks, the ability of the human body to suppress infection was reduced.
The combined use of Avonex and Tysabri leads to a rapid accumulation of Tysabri.
The combined use of Avonex and Tysabri leads to a rapid accumulation of Tysabri after a relatively short period of time (approximately 20 weeks).
Defendants knew that after administration of the combination therapy for 20 weeks, the average concentration level of Tyrabri increased approximately eighty-six (86%) percent over the levels that would have developed if Tyrabri had been used in mono-therapy.
The combined use of Avonex and Tysabri reduces the ability of the body to clear Tysabri.
The combined use of Avonex and Tysabri reduces the ability of the body to clear Tysabri after a relatively short period of time (approximately 20 weeks).
Defendants knew that after administration of the combination therapy for 20 weeks, the clearance rate of the level of Tysabri decreased by forty-eight (48%) percent as compared to the levels that would have developed if Tyrabri had been used in mono-therapy.
The combination use of Avonex and Tysabri increases the half-life of Tysabri after a relatively short period of time (approximately 20 weeks).
The accumulation, clearance and half-life of Tysabri, as a result of the effects of Avonex, resulted in almost doubling of the intended level of Tysabri a relatively short period of time (approximately 20 weeks).
Defendants knew that after administration of the combination therapy for 20 weeks, the half-life of Tyrabri increased by fifty-four (54%) percent as compared to the levels that would have developed if Tyrabri had been used in mono-therapy.
As a result of the data and/or information that the defendants were in possession of, the defendants knew and/or should have known that, when used in conjunction with Avonex, Tysabri would accumulate in patients over time in an amount in excess over that which was inteded, desired and/or safe.
As a result of the data and/or information that the defendants were in possession of, the defendants knew and/or should have known that increased concentations of Tysabri was likely to occur as a result of the combination therapy, which higher concentrations of Tysabri would be greater than intended, desired and/or safe.
As a result of the data and/or information that the defendants were in possession of, the defendants knew and/or should have known that signficantly higher concentrations of Tysabri above that which was intended, desired and/or safe, would expose patients to increased immunosuppression than if treated with Tysabri alone.
Based on all of the available data, Biogen and Elan should have conducted long-term studies before ever testing Tysabri on human subjects.
Anita Smith was never warned of the cumulative effect and long-term risks of Tysabri or the combination therapy.
At no time did the Defendants disclose to Mrs. Smith, and/or plaintiff, or other participants in the clinical trials that included Tysabri, that scientists within, and/or consultants of, the defendants’ companies (including predecessor companies), warned of the dangers of using Tysabri in humans.
At no time did the Defendants disclose to Mrs. Smith and/or plaintiff, or other participants in the clinical trials that included Tysabri, that literature in professional journals questioned the use and/or safety of Tysabri in humans.
On March 1, 2005, The New York Times published an article in which a leading expert on Tysabri who participated in its original development stated that no one should have been surprised that patients being treated with Tysabri would contract PML. In this regard,the article stated, in relevant part:
Lawrence Steinman, a professor of neurology and head of immunology at Stanford, said the F.D.A. should not have approved the drug on the basis of only one year’s data. He said the risk of serious infections like P.M.L. was ”unfortunately logical” given that Tysabri works by interfering with the immune system.
“I’m shocked that it happened so soon, but I knew it was going to happen sooner or later,” said Professor Steinman, who participated in an early animal study that led to the development of Tysabri. Dr. Steinman is a co-founder and director of Bayhill Therapeutics, a company developing competing drugs for multiple sclerosis.
Dr. Steinman said he had expressed his apprehensions about the drug in speeches and in an article in the journal Science in July and had been asked by Biogen executives to tone down criticism of the drug. [Emphasis added.]
On March 9, 2004, the Los Angeles Times published an article providing specifics with respect to the infection rate and adding that FDA officials lacked sufficient information about Tysabri’s long-term effects. The article stated, in relevant part, as follows:
In hundreds of pages of documents that offered the first detailed look at the FDA’s handling of the drug, reviewers noted that Tysabri appeared more effective than existing drugs, reducing relapses in patients by 66%, based on one year’s data. The reviewers said it was "reasonably likely" that the drug would provide long-term benefits.
Nonetheless, the agency’s drug reviewers acknowledged they were unsure about Tysabri’s long-term effects.
"The clinical meaningfulness of a decrease in the incidence of relapses at one year is uncertain," the reviewers wrote.
FDA reviewers found that Tysabri had an acceptable safety profile, though they noted that health risks "beyond one year are not known."
Infections, including urinary and respiratory, were seen with Tysabri, but they were "generally routine and did not have a complicated course," the reviewers said.
Stanford University professor Dr. Lawrence Steinman, an MS specialist, had warned there was a clear risk of infection for patients taking such drugs, because they tend to suppress the body’s immune system.
Steinman had helped discover the active agents in the drug, but later became concerned about potential side effects, and is working on a competing drug. He noted that the infection rate of Tysabri patients in one trial was 2.1%, compared with 1.3% in the placebo group.
"There were hints of an increase in the infection rate," said Steinman. "The FDA should have dug deeper." [Emphasis added.]
Prior to and during Mrs. Smith’s participation in the subject clinical trial, the defendants knew or should have known, and failed to disclose, that animal and/or human studies that included Tysabri showed a significant risk of adverse effects resulting from suppression of the immune system.
The lawsuit has 14 separate causes of action on behalf of the estate of Anita Smith, for her conscious pain and suffering, and for her husband’s derivative claims arising out of the death of his wife.
The causes of action also include fraud, deceptive practices, and punitive damages for “ defendants’ malicious, wanton, malicious, willful, wanton, grossly negligent and/or reckless conduct.”
While MS patients and parents of children with MS are now concerned that what appeared to be a promising medication may never make it back on the market, many experts in the field of pharmaceutical development regard Tysabri as a dangerous drug that never should have been approved by the FDA in the first place.
There is also the claim that Tysabri should not have been used in human trials before thorough long-term studies were conducted.
Most of all, however, there appears to have been ample evidence in the form of test data and opinions from highly qualified and credible experts that this drug posed a serious risk of the very injuries (and deaths) that ultimately occurred.
Certainly, PML was always a possible risk due to the immunosuppressive quality of the drug. This factor made the combination therapy of two such drugs (Tysabri and Avonex) problematic and worthy of serious consideration (and appropriate warnings) before it was routinely prescribed to patients in the clinical trial.
Finally, it appears that Anita Smith was functioning well without this drug and would probably have lived a normal lifespan with her husband and children. Thus, if the allegations in the complaint are true, the terrible circumstances under which she died were preventable.