Adverse events data for Acthar hint at problems

ANAHEIM HILLS, Calif.—“When Questcor purchased Acthar in 2001 we were rescuing an old drug that was being abandoned by “Big Pharma,” states company President Don M. Bailey in an extraordinary 2,200-word Letter from the President and CEO on the Questcor website, adding that “This was a serious public health concern to the FDA.”

Indirectly taking exception to these assertions, the New York Times has noted that “For years, Questcor Pharmaceuticals has highlighted the potential benefits of Acthar, its immune-system drug, while saying little about its ill effects,” in an article that provided details on the first-time reporting of adverse effects by Questcor. According to the Times, the regulatory filing made by Questcor early Thursday, stated that the number of patients reporting a so-called adverse event while using the drug last year represented almost 5 percent of prescriptions dispensed. The total number of events in 2013 reported by patients, who can experience multiple ill effects, was almost 14 percent of prescriptions, up from 9.1 percent in 2011.

It was the first time Questcor, which has received a $5.6 billion takeover bid from Mallinckrodt Pharmaceuticals, had disclosed any problems experienced by Acthar patients. Disclosure followed a report last month in the Times analyzing adverse events data on Acthar from the Food and Drug Administration.

From Jan. 1, 2011, to Dec. 31, 2013, Questcor said, 1,022 patients reported 3,100 adverse events while on Acthar. The filing said that many users of the drug were seriously ill and faced life-threatening health risks. Acthar generates some 95 percent of Questcor’s revenues.

The data, which was obtained by the Times under the Freedom of Information Act, showed 20 deaths and six disabilities since 2012 among patients reported to have been using Acthar and in which Acthar was recorded as “suspect,” or the drug most likely to have been associated with the event. From January 2000 through 2011, by contrast, 13 deaths involving Acthar were submitted to the FDA’s adverse events reporting system.

When asked last month why the company had not disclosed these events, a spokeswoman quoted by the Times said that the safety profile of Acthar was well known. CEO Bailey has also said that “Acthar is an approved product that has been on the market for sixty years, so its safety profile is very well known and is supported by decades of clinical use.”

Bailey in his Acthar apologia is keen on emphasizing the positive. “Much of the medical community mistakenly regarded Acthar as merely a way of stimulating the adrenal gland to secrete natural endogenous steroids. Since synthetic steroids appeared at that time [1952] to be an inexpensive direct substitute for Acthar, R&D spending on Acthar essentially came to a halt for the next several decades,” Bailey laments.

“But the focus of our story is that Acthar is not a steroid. Instead, it is a complex formulation which includes adrenocorticotropic hormone (ACTH), a melanocortin peptide that is reported to bind a family of important receptors known as melanocortin receptors. Importantly, we are also learning that Acthar may potentially include other active peptides as well. But the key to Acthar is that it appears to bind to melanocortin receptors found in a variety of the body’s own organs and systems, including the central nervous system, the kidney, and certain key immune cells. One of these receptor types is also found on the adrenal gland, where their binding by ACTH stimulates the production of the natural steroid cortisol. Thus, there appear to be multiple Acthar mechanisms of action, of which only one element is steroid-related. For this reason, many doctors tell us that Acthar can be a useful treatment alternative in some patients who have not had overall success with treatments traditionally used for their condition. Acthar has historically been misunderstood, underestimated and under-resourced, and what many physicians think they know about the drug is not up-to-date. We are working hard to change this. As such, Acthar is now undergoing a renaissance in multiple fields of medicine – neurology, nephrology, rheumatology, and, we hope, pulmonology. This represents our opportunity and our challenge in rescuing and reviving this neglected old drug from which many thousands of patients are now benefiting.

None of the “many physicians” Daily cites is named, nor is how or for what indications they may be prescribing Acthar specified. In its Clinical Development Programs and Pipeline page on its website Questcor lists five Acthar studies as in Phase 2 to Phase 4 status. When the “more information” link is clicked you are told that you are leaving the Questcor website and offered the opportunity to cancel. If you continue, here are the indications currently said to be under study: ALS, Phase 2, ongoing but not recruiting patients; proteinuria in membranous nephrology, Phase 4, recruiting patients; diabetic nephropathy, Phase 2, recruiting patients; lupus, Phase 4, ongoing but not recruiting patients; acute respiratory distress syndrome, Phase 2, not yet open.

Bailey notes in his letter that “… we have invested heavily in developing an experienced and well-trained commercial team to educate physicians about our growing understanding of Acthar and its ability to help their patients. Our representatives are highly experienced and have often spent most of their careers educating doctors about the proper use of advanced new biological medicines. Physicians are also supported by a growing team of Medical Science Liaisons, most of whom are PhDs, PharmDs or MDs, who respond to medical inquiries and provide technical information to healthcare providers regarding the growing body of scientific and clinical evidence related to Acthar.”