Pennsylvania Record

Wednesday, October 16, 2019

Ex-FDA commissioner says Risperdal was promoted for kids before it was approved; J&J maintains it was safe

State Court

By Nicholas Malfitano | Sep 20, 2019


PHILADELPHIA – Testimony in the Risperdal punitive damages trial continued Thursday with the lengthy, taped testimony of a former Food & Drug Administration commissioner who said Johnson & Johnson and its subsidiary Janssen Pharmaceuticals sought to promote use of Risperdal in children and adolescents, before it was given such approval – but the company maintains it was safe for that age group.

The trial is notable as Philadelphia’s Complex Litigation Center houses thousands of similar claims from out-of-state plaintiffs, and the city has a reputation for high-dollar verdicts. It's the first time in Philadelphia that a jury can consider assessing punitive damages in a Risperdal case and also another front the company must fight as it litigates opioid, talcum powder and other mass tort cases elsewhere.

In Murray v. Janssen Pharmaceuticals, involving Maryland plaintiff Nicholas Murray, a jury decided the case in Murray’s favor in November 2015 and awarded him $1.75 million. The $1.75 million jury verdict represented damages for “disfigurement and mental anguish," though it was later cut down to $680,000.

For the second trial, plaintiff counsel will attempt to prove that the companies deliberately disregarded evidence that Risperdal could lead to gynecomastia, or the development of breast tissue, in young males and nonetheless released the drug into the open market for prescription and use by patients without disclosing the side effects.

Murray was prescribed Risperdal at the age of nine in 2003, for off-label treatment of symptoms associated with his Asperger’s Syndrome. Like other plaintiffs who stepped forward, Murray also contracted gynecomastia.

Dr. David Kessler Provides Direct Testimony to Plaintiff Counsel

Dr. David Kessler, FDA commissioner from 1990 to 1997 under the administrations of both President George H.W. Bush and President Bill Clinton, testified over two days through a videotaped deposition that had been filmed in May 2015.

In direct examination, Kessler referred to a 2002 internal business plan from Janssen that, looking ahead to 2003, showed information pertaining to proposed and actual budgets for marketing the medication to children in the coming year.

According to Kessler, these budget plans are usually provided to the highest levels of a company’s administration.

However, Kessler added Risperdal had not been approved for use by children at that time – and despite that, employees of Janssen made presentations at advisory meetings on the efficacy of the drug in children and adolescents.

According to Kessler, one such example was a presentation made by Janssen Senior Director of Clinical Research Dr. Gahan Pandina in Los Angeles in August 2003, at a Child & Adolescent Regional Advisors Meeting on the subject of disruptive behavior disorders, such as autism and acute mania.

Kessler explained with data having shown that there was an association between elevated levels of prolactin and adverse reactions to the drug, an advisors meeting like the one attended by Pandina was a “perfect opportunity” to warn of the side effect.

“Here was a perfect opportunity to tell physicians there was a red flag,” Kessler said.

Kessler continued that Janssen’s sales teams were given documents on Risperdal that didn’t mention a study’s 2.3 percent rate of gynecomastia among 1,885 child patients and, referring to a 2002 label for the drug, classified endocrine disorders associated with the condition, such as gynecomastia, male breast pain and anti-diuretic hormone disorders as “rare.”

In 2007, Kessler said new labeling information for Risperdal mentioned warnings for hyperprolactinemia, or elevated levels of the hormone prolactin, in the bloodstream and described the drug as being associated with higher levels of prolactinemia than other anti-psychotic agents.

Though it mentioned reported cases of gynecomastia, Kessler contended the post-2006 drug label was inadequate in that it did not discuss the statistically significant association between Risperdal and hyperprolactinemia.

Kessler indicated that the company and its sales teams did not warn of incidence of elevated prolactin levels from clinical studies, like INT-41, and their internal business plan did not mention higher rates of hyperprolactinemia and gynecomastia.

“A reasonable and prudent manufacturer would certainly want to provide [such] safety information,” Kessler said, adding that label regulations do not prohibit a manufacturer from warning about a drug’s side effects.

When asked by plaintiff counsel Tom Kline if the company’s actions were outrageous and showed reckless disregard, Kessler said yes.

“In light of the fact that off-label promotion is concerning, the use of a very powerful medicine is something that has to be taken very seriously. When risks are not disclosed to the most vulnerable of our children, that is reckless,” Kessler said.

“When you sell Risperdal for indications that are not approved, you expose more children to that risk. That conduct, plus the context, is reckless. You’re doing this with a drug described as a chemical straitjacket to children who are mentally impaired. It is upsetting.”

Johnson & Johnson Counsel Cross-Examines Dr. Kessler

In the next part of the videotaped deposition of Kessler, defense counsel John D. Winter cross-examined the former FDA Commissioner for more than three hours.

Johnson & Johnson counsel referred to studies conducted and published that affirmed Risperdal for use by children and adolescents, as well as the lengthy process of approval correspondence between the company and the FDA

In one example, Winter pointed to a 2006 article from Dr. Magali Reyes titled, “Long-Term Use of Risperidone in Children with Disruptive Behavior Disorders and Subaverage Intelligence: Efficacy, Safety, and Tolerability."

That trial included 35 children from ages six to 16, who were diagnosed with disruptive behavior disorder and had IQ’s ranging from 35 to 84. All subjects had previously completed a one-year, open-label Risperdal study, and an extension study followed them for two more years of treatment.

In Dr. Reyes’s paper, she found that “continuing low-dose risperidone for up to 3 years appears to be safe and effective in children with disruptive behavior disorders.”

Approvals were granted by the FDA for Risperdal use by pediatric patients experiencing both schizophrenia and bipolar mania, and later for irritability symptoms associated with autism in October 2006.

Though it was agreed by Winter and Kessler that the FDA has some leverage over the final wording of a drug’s label, Kessler advocated caution over the use of the word “leverage.”

“It can ask a company to do certain things, but be careful with the word ‘leverage’, because the FDA is only as good as the information it receives,” Kessler said.

Among other exhibits, Winter also pointed to documents from medical safety reviewers Dr. Lourdes Villalba and Dr. June Cai, who explained that the company responded affirmatively to their feedback to include information about elevated prolactin levels in patients for pediatric clinical trials.

“In negotiation, the FDA made suggestions and the company agreed. Is that fair? And that language ended up in the labeling,” Winter asked of Kessler.

Cai further wrote, “I conclude the sponsor has submitted sufficient data to support efficacy and safety of risperidone in irritability symptoms associated with autism in children and adolescents.”

Kessler commented that the FDA may not have had all pertinent information when stating that.

“Based on what Dr. Cai saw as the data, she made that judgment. But she may not have had all the data,” Kessler said.

In another document, a heading titled “Safety Data” showed that “treatment of pediatric patients with risperidone has been reasonably safe and well-tolerated” and “the safety profile in pediatric patients appears similar to that of adults.”

Another heading titled “Laboratory Findings” read, “Risperidone increases mean prolactin levels from baseline to endpoint. Increases were dose-dependent and clinical relevance of such increases is unknown.”

Yet another section titled “Conclusions & Recommendation” read, “The sponsor has submitted sufficient data that risperidone is effective and reasonably safe in pediatric schizophrenia and bipolar I disorder patients, and should proceed with an approvable letter saying so.”

Kessler again remarked that the medical reviewers in question may not have been provided all relevant data to make that determination.

Philadelphia County Court of Common Pleas case 130401990

From the Pennsylvania Record: Reach Courts Reporter Nicholas Malfitano at nick.malfitano@therecordinc.com

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Organizations in this Story

Janssen Pharmaceuticals, Inc. Johnson & Johnson Kline & Specter PC

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