What Allergan Proposes in its "Free-Speech" Complaint

In its recent "free-speech" complaint for declaratory judgment and injunctive relief against the US government, Allergan proposes its "speech" to healthcare providers about the risk of Botox spread after injections for spasticity—an off-label indication. But the company logically fears that its proposed speech, which would include only truthful, nonmisleading statements about the off-label use of Botox, puts it in criminal and civil jeopardy. (For background on this story and the FDA's safety requirements re Botox risks, go here.)

First Allergan claims that the FDA-approved boxed warning for Botox,* the mandated Dear Health Care Provider letter, and altered Medication Guide provide only general warnings about the distant spread of toxin. These communications do not provide specific guidance for physicians**—for instance, details about patient selection, toxin dose, number of injection sites, frequency of administration, and injection technique—that would tangibly reduce the risk of remote spread when using Botox for spasticity. Allergan also proposes that it would inform physicians about the expected time frame to observe a therapeutic effect with Botox, when used for spasticity.

Allergan acknowledges that its proposed speech would not alter the official labeling for Botox, but the company recognizes that much of its proposed speech would "fall within the FDA's expansive definition of 'labeling'" and could lead to federal misbranding charges. Discussions about the safety of Botox treatment for spasticity may also be interpreted as promoting Botox for spasticity, and such an interpretation could lead to federal charges of distributing an unapproved "new drug" in the eyes of the FDA (meaning, an existing drug for a new indication).

Following the logic a step further, Allergan writes: "Even by filing this complaint and thereby exercising its First Amendment right to petition the Government, Allergan fears that it will run afoul of the FDA's regulatory regime by demonstrating its knowledge that Botox is sold to physicians who use it to treat spasticity and other off-label conditions. On the Government's view, Allergan's possession of this knowledge—and its choice to defend its constitutional rights—violates 21 CFR §201.128 [which relates to the drug maker's knowledge of intended uses] on its face."

Allergan justifies its fear of prosecution for the off-label promotion of Botox by acknowledging that the company is the subject of a DoJ investigation in the Northern District of Georgia.

* Text of boxed warning advising of distant spread of toxin: "Postmarketing reports indicate that the effects of Botox and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children and adults, and in approved indications, cases of spread of effect have occurred at doses comparable to those used to treat cervical dystonia and at lower doses."

** Allergan reports that it "does not seek to engage in direct-to-consumer communications about the off-label use of Botox."