Court-Ordered Access To Experimental PTC Drug Shows Risks Of Patient Outreach

A judge's decision to order PTC Therapeutics to provide an experimental drug for a teenage boy with Duchenne Muscular Dystrophy highlights the need for caution in communications with patients and their families, particularly in cases of life-threatening disease.

In a preliminary injunction released Aug. 21, New Jersey federal judge William Martini advised South Plainfield, N.J.-based PTC to provide access to PTC124, now in Phase II testing, to 16-year-old Jacob Gunvalson, via a treatment IND.

The plaintiffs - Jacob's parents - had argued that the boy held off on entering a 2006 Phase IIa trial with PTC124 in nonsense mutation DMD, based on verbal assurances from executives that he could take part in later trials. But as it happened, he was not eligible for those studies.

The Gunvalsons sued after PTC denied a request to provide the drug to Jacob as an individual patient through a compassionate use program.

Helping form the court's decision was the 1993 Dahl v. HEM Pharmaceuticals case, in which Hemispherx Biopharma was ordered to provide Ampligen (Poly 1:Poly C12U) through the compassionate use exception. Trial participants claimed they had been promised by the company that they could continue taking the drug if it proved effective against placebo.

According to Martini's decision, all communications in the muscular dystrophy case must be viewed in light of the "unique relationship" between PTC and Jacob's mother Cherie, a lobbyist for DMD research funding with "close ties to PTC employees and officers."

Statements showing the "social" nature of the relationship between PTC vice president Claudia Hirawat and Cherie Gunvalson were particularly influential in the case.

"It is undisputed that Cherie and Jacob have even stayed overnight at Hirawat's home on at least one occasion. Because of these extended connections alone, it seems to the Court that PTC would be more likely to communicate to plaintiffs more compassionately and less formally than with other parents of DMD children," Martini wrote.

Though PTC argued that it never promised treatment in the future, the judge interpreted certain statements in Hirawat's affidavit as contrary to this claim.

Impact On Communications

The case shows that the sponsor/patient relationship created expectations that could be enforced based on contract theory, said Arnold Friede, an attorney with McDermott Will & Emery in Washington, D.C.

"Communications need to be carefully controlled so expectations are mutually understood and agreed in writing," said Friede, adding that the judge's finding in the case seems reasonable, based on the facts presented.

PTC said it appeals the decision, which "sets an unfortunate precedent for companies wishing to work closely with patients and their caregivers and advocates." However, the firm's request to hold action pending an appeal was denied.

Martini rejected PTC's argument that granting access to the drug would harm the company and the public by "opening the floodgates to all DMD sufferers who might use litigation to obtain PTC124 without participating in clinical trials."

"This is a unique case in that PTC appears to have promised this drug to plaintiffs. An injunction here will not have implications beyond this case," he wrote.

While the case "might encourage companies to become a little more buttoned up in their communications," Friede said, it is unlikely to have "broader implications in the conceptual debate about early access" to investigational drugs, because the decision was based purely on contract theory.

Case Shows Need For New Trial Endpoints

Jacob Gunvalson held off on participating in the 2006 Phase IIa trial of PTC124 because at the time he was taking another medication that conflicted with study protocol.

Later, he could not join a continuation Phase IIa trial absent participation in the initial Phase IIa study, and he was not eligible for a new Phase IIb study because his condition had worsened and he was no longer ambulatory.

All DMD trials use walking tests as endpoints to measure progress; exclusion of non-ambulatory patients is a "major problem," said Sharon Hesterlee, vice president of translational research for the Muscular Dystrophy Association, which helps fund PTC trials.

As disease progresses, patients may lose their ability to walk - between the ages of 12 and 14 in some cases - but life expectancy runs to the mid 20s and early 30s. Therefore, a significant part of the DMD population is unable to take part, she said.

"Parents rightly feel their sons are forgotten because they can't participate in trials. I understand where the urgency comes from," Hesterlee said.

The MDA has been in talks with PTC to do a study investigating new kinds of endpoints for DMD trials, but ironically, the Gunvalson lawsuit is distracting and has been slowing down this process, she said.

Patient Advocates Support The Company

Though sympathetic to the Gunvalson's predicament, the MDA generally sides with the company, partly due to concerns about fairness.

"Who is to say that all boys with the mutation couldn't potentially take the drug? It's a slippery slope. You can't put everyone on a drug that is not paid for," she said.

Typically, drugs made available through the compassionate use exception are backed by more substantial efficacy data than what is available for PTC124 in DMD, and there are also safety concerns, she said.

"If someone outside a trial has an adverse event, it will be reported to the FDA and the trial could be shut down," she said.

The DMD community is largely supportive of PTC and wants research to proceed unhampered, Hesterlee said, adding that she expects the case will be overturned because a wave of successful suits would cause the research system to collapse.

Advocacy groups and judges are well aware of the dangers in encouraging people to use the courts to get access to new drugs instead of participating in placebo-controlled trials, said attorney Bradley Thompson, of Epstein Becker & Green.

Many patient groups, Thompson points out, opposed the plaintiffs in the Abigail Alliance case, who unsuccessfully sued FDA to establish a constitutional right for terminally ill patients to receive investigational drugs (¹ (Also see "Abigail Alliance Presses For Access To Drugs With Troubled Regulatory Pasts" - Pink Sheet, 21 Jul, 2008.), p. 14).

In two other cases - Abney v. Amgen and Suthers v. Amgen - patients unsuccessfully sued to continue receiving an investigational Parkinson's disease drug after a trial ended.

The Gunvalson case is "truly unique," Thompson said, in that the plaintiff is not arguing a statutory right to the medication or challenging FDA regulations; rather the case involves a quasi-contract through a set of communications between the patient and the company.

"The case could have a chilling effect on companies talking to patients if they had to fear that somehow they were creating an expectation about access to a drug," he said.

How Companies Should Communicate

The Muscular Dystrophy Association's Hesterlee points out, however, that while PTC executives seem to have had the best intentions, it is unusual for study participants to stay at the house of company executives and a professional line may have been crossed.

Some companies - notably Genzyme, which in July announced plans to partner with PTC on PTC124 - have become very good at carefully defining good relationships with patients, she said. Patient groups can provide a buffer and help prevent PR problems.

"Genzyme clearly understands the value a nonprofit brings in rare diseases as gatekeepers of information. Genzyme channeled a lot through us and other organizations," she said.

PTC's contact with MDA, in contrast, has been minimal, but that could change now that Genzyme is on board, she said.

- Emily Hayes ([email protected])