The NYT Misses in its Coverage of Iplex and ALS
Last weekend’s NYT featured a lengthy story on ALS victim Joshua Thompson (“Fighting for a Last Chance at Life“) and his struggle to obtain access to the investigational drug Iplex (from Insmed) on a compassionate basis. Like most patient-centered articles in the mainstream press, the feature is heart breaking…and arguably irresponsible.
In what turns out to be really a very cloying piece, writer Amy Harmon takes the usual easy, uninformed (or perhaps just uninformative) road in pharma journalism by 1) stressing the ostensibly cruel indifference of corporate America and FDA bureaucracy; 2) downplaying the total absence of clinical data to support the use of Iplex in ALS; and 3) completely sidestepping the issue of poor medical policy as bullied into existence by an Internet-fueled public.
So here’s the…
Iplex, a synthetic insulin-like growth factor (IGF-1) that is linked to a binding protein (IGFBP-3), was FDA approved in December 2005 for the treatment of growth failure in children with severe, primary IGF-1 deficiency. The drug received a priority review and was designated an orphan drug, because of the rarity of its indication. But Iplex was removed from the market in early 2007 after Insmed settled a patent dispute with Tercica and Genentech. These companies held the patent on a similar rival drug, Increlex, a synthetic IGF-1 without the binding protein. Increlex was FDA approved in August 2005 for the same rare condition.
In its defense, Insmed pleaded that Iplex should be made available and its development continued, given the drug’s other potential indications, including ALS and multiple sclerosis. Proponents also argued that the drug’s distinctive binding protein (in contradistinction to Increlex) facilitates entry of IGF-1 into the central nervous system—a purely theoretical proposition. Bolstering Insmed’s argument was the fact that the Italian Ministry of Health had asked Insmed to make Iplex available to the country’s ALS patients, despite the fact that no clinical (or even published preclinical) data existed to support the drug’s efficacy or safety in the condition. Through several court rulings, Insmed then worked out a deal with Cephalon, the European patent owner of IGF-1, to provide Iplex to about 100 Italian citizens in an expanded access program (which the government paid for, to the tune of $100,000 USD per patient per year).
In the United States, some ALS patients had acquired Iplex off label before the drug was pulled. In online testimonials, these patients crowed about the drug’s benefits—thereby prompting individuals like Joshua Thompson and their families to invest tremendous hope, time, and effort in acquiring Iplex by whatever means necessary. Thompson even contemplated moving to Italy, until he discovered that Iplex was only available to Italian citizens.
Harmon chronicles the crusade of Joshua’s mother, Kathy, to get compassionate access to the unproven drug for her son. Perhaps most disturbing is Harmon’s unwitting example of the insidiousness of the online testimonial: Because of a single forum post maligning the effect of Increlex, when compared with Iplex, Kathy Thompson believed that only Iplex would help her son.
IGF-1 Clinical Data Disappoint
Up until recently, results of well-controlled clinical studies of subcutaneous IGF-1 (Increlex) were mixed. In a double-blind, placebo-controlled, randomized trial of 266 North American ALS patients, IGF-1 significantly slowed the progression of functional impairment in an apparent dose-dependent fashion. However, a similarly designed European study (N = 183) showed no benefits with IGF-1 treatment in ALS. Then last year, results of a definitive, phase 3 trial (N = 330) revealed no difference in the primary or secondary outcomes between IGF-1- and placebo-treated ALS patients at 2 years.*
The negative clinical-trial results with IGF-1 in ALS apparently eased the way for compassionate access to Iplex in the United States, since Tercica and Genentech could not hold a competitive position in this therapeutic area. More important, safety data provided to the FDA by the Italian Ministry informed the agency’s decision to grant restricted access to Iplex. So in March of this year, the FDA—bowing to the grass-roots demand for Iplex from Kathy Thompson and others—decided to allow access to the drug under an IND application. This decision was made to the consternation of several ALS experts (for excellent and more detailed coverage of this story angle, see the May 4th issue of Neurology Today). The 2 methods by which American ALS patients could (or can) obtain Iplex: 1) a single-patient IND application to the FDA that had to be received by March 6, 2009,** and 2) a randomized clinical trial.
Through his single-patient IND, Joshua Thompson received his first dose of Iplex on March 25th. An NYT epilogue reveals that Joshua reported subjective improvement in his swallowing with treatment; however, on April 12th, he was hospitalized with pneumonia and placed on mechanical ventilation, where he evidently remains.
ALS = amyotrophic lateral sclerosis; IND = investigation new drug.
* A small, double-blind trial of 2 doses of intrathecal IGF-1 in Japan (N = 9) provided mixed, but largely disappointing, results.
** Harmon writes that it’s unclear who’s paying for the drug.