Targeted Genetics Responds to Wired Science Criticism

Targeted Genetics CEO H. Stewart Parker recently criticized Wired Science’s coverage of the company’s controversial gene therapy trial for arthritis.

The trial, halted in July after the death of 36-year-old Jolee Mohr and recently cleared by the FDA to restart, involves a drug called tgAAC94. The drug is composed of a virus that delivers an immune system-suppressing gene into the cells of arthritic joints. Thus suppressed, the cells are supposed to stop making the inflammation-inducing proteins that make arthritis so painful.

Jolee Mohr died within weeks of receiving tgAAC94, her body ravaged by a fast-spreading fungal infection, but doctors weren’t sure whether to blame gene therapy. The infection, called histoplasmosis, is a reported side effect of Humira, an immune system-suppressing arthritis drug also taken by Mohr during the trial.

Eventually they determined that gene therapy didn’t cause the infection. But Kyle Hogarth, a University of Chicago pulmonologist who tried to save Mohr’s life, criticized Targeted Genetics for conducting early-stage research in such a confusing — even careless — way: If you’re trying to understand a new drug, why study it in people who are already taking a similar drug? Wired Science posted Hogarth’s criticisms two weeks ago. In response, Targeted Genetics CEO H. Stewart Parker posted a lengthy rebuttal. Wrote Parker,

Several assertions have been made in Mr. Keim’s blog that are inaccurate and incorrect. First, prior to the current Phase I/II trial, Targeted Genetics completed a Phase I trial of tgAAC94 in patients who were not on current anti-TNF systemic therapy. No safety problems were encountered in that trial. With that data in hand, Targeted Genetics requested and received authorization to conduct the current Phase I/II trial. Patients in this trial can be, but do not have to be, on concomitant anti-TNF therapies. Indeed, it is the scientific premise of the research that the study drug will provide symptomatic relief and improved outcomes for a group of patients who have been treated and may still be undergoing treatment with anti-TNF systemic therapy. The Phase I/II trial was therefore designed to determine whether the study drug will be safe and effective when used in combination with (or while patients are also taking) a systemic therapy used to treat inflammatory disease.

It is unfortunate for the sake of objectivity that Mr. Keim has not quoted experts in rheumatology clinical trial design to balance the comments made by others who are not experts in the field.

Kyle Hogarth, M.D., of the University of Chicago is a pulmonologist who treated Ms. Mohr during her decline. Leaving aside Dr. Hogarth’s potential bias as an attending physician who was involved with the clinical treatment of the patient, it is not clear that Dr. Hogarth has any education, training or professional experience that makes him qualified to comment that the design of the clinical study was flawed because the study drug was administered in combination with other medications that study participants may have been taking for treatment of their inflammatory disorders. He is not a specialist in rheumatology, the field of medicine most associated with the treatment of the disorders this patient suffered from that caused her to participate in the study in the first place. Dr. Hogarth certainly is not in a position to discredit a study design that was approved by the regulatory agencies charged with responsibility for oversight of gene therapy research of this sort. Indeed, Dr. Hogarth is incorrect in his assertion that best practices require that all Phase I trials should be conducted using a monotherapy approach for the investigative agent.

Parker’s criticism of Hogarth is disingenuous and unfair. "Leaving aside Dr. Hogarth’s potential bias as an attending physician," she wrote — which is a clever way of saying that we ought to consider his bias. Parker is ill-placed to cast such aspersions; but leaving aside her potential bias as the CEO of a struggling company that could go bankrupt if its still-experimental flagship treatment fails, Hogarth was in a position to comment on Mohr’s trial because he was one of the people charged with picking up the pieces.

But if Hogarth’s qualifications might be questioned, that’s certainly not the case with Peter Lipsky, the editor-in-chief of Nature Clinical Practice Rheumatology and Autoimmunity Branch chief at the National Institute for Arthritis and Musculoskeletal and Skin Diseases. I asked Lipsky today about Hogarth’s criticisms and Parker’s reponse. Said Lipsky,

If you search for other trials in which two anti-TNF drugs are being used at the same time your search will most likely be fruitless.

It’s very unusual to have a trial in which two anti-TNF agents are used. It becomes very difficult to interpret data when you’re using a drug that targets, very precisely, a specific biological mediator in an individual who is already having that mediator targeted.

Image: John Beeler

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• Targeted Genetics Fires Back at Washington Post, but Evades Charges

• Gene Therapy: Is Death an Acceptable Risk?

• How to Run a Better Clinical Trial

• The Ethical Challenge of Gene Therapy Trials

• Tests Clear Gene Therapy of Jolee Mohr’s Death, but Targeted Genetics Doesn’t Learn Lesson

• Controversial Gene Therapy Trial Was Poorly Designed, Says Doctor

• Controversial Gene Therapy Trial Restarts