Cancer Drug Returns, and with it FDA's Willingness to Go After its Manufacturer

Earlier this week, the US Food and Drug Administration (FDA) made a quiet but important announcement: Supplies of the drug Doxirubicin Liposomal Injection, a widely used cancer drug that has been experiencing massive shortages since 2011, have been resolved. But with the resolution of that shortage has come something else that has been in short supply in recent months as well: regulatory scrutiny for the drug.

Background

In late 2011, regulators became aware of mounting drug shortages they said were caused by several factors, but most notably manufacturing problems found at a number of facilities that made sterile injectable drugs like Doxil (doxorubicin). Those problems caused the facilities to be shut down, creating difficulties for many patients and physicians who said they either could not find any supplies of the drug available, or did not have a sufficient amount of the drug to ensure a complete treatment regimen could be followed.

In the wake of mounting public outcry, FDA Commissioner Margaret Hamburg announced in February 2012 that the agency would be working with Sun Pharma FZE to allow for the limited import of a Doxil substitute, Lipodox, manufactured at an FDA-inspected facility in India.

"We are confident using regulatory discretion to ensure the safety and utility of this product," FDA Associate Director Valeria Jensen, head of FDA's drug shortage program, said at the time. The agency went on to approve the drug a year later in February 2013, ending the use of discretion in that particular case.

February 2013 brought other good news for Doxil, as regulators signed off on a consent decree that allowed Ben Venue Laboratories, the site that once manufactured the drug, to resume limited manufacturing operations. And while the drug's sponsor, Janssen, said a shortage situation still existed as of a week ago in a 30 May 2013 letter to healthcare providers, FDA's 4 June 2013 update to its list of products experiencing shortages cleared the drug of any problems, noting that the "product is currently available" from Janssen and Sun Pharma.

Untitled Letter

But even as patients may be celebrating their ability to obtain Doxil more easily, Janssen might not be quite as pleased. That's because in late May 2013, just as shortages were showing signs of abating, FDA sent the company an Untitled Letter chiding it for improperly marketing the drug on its website using unsubstantiated claims, rendering it misbranded.

The 22 May letter references claims made against the drug's label for ovarian cancer, a condition for which it has received FDA approval. The problem, regulators said, it that the marketing materials for the drug contain an entire section claiming an association between levels of a biomarker (the CA-125 biomarker) and clinical responses to Doxil therapy.

Such an association has "not been demonstrated by substantial evidence or substantial clinical experience," regulators wrote. Janssen's materials reference several retrospective evaluations of primary data that did not meet federal standards for evidence.

FDA's Office of Prescription Drug Promotion (OPDP) called for Janssen to immediately cease the dissemination of the marketing claims. As of the time of publication, that webpage appears to have been removed in its entirety, though a link to a non-existent webpage on the topic still exists here.

The letter is the first to be sent to Janssen since Doxil began experiencing shortages, potentially reflecting a new willingness of the agency to focus on regulatory improprieties associated with drugs once their shortages ease or end.

Untitled Letter to Janssen