AbbVie's Duopa successor in Parkinson's rejected again after FDA flags 3rd-party manufacturer issues

A little over a year after being slapped with an FDA rejection, AbbVie has hit another regulatory wall in its bid to debut a more convenient Parkinson’s disease successor to its established formulation of carbidopa and levodopa.

The U.S. Food and Drug Administration (FDA) has once again rejected AbbVie’s ABBV-951 for controlling motor fluctuations in patients with advanced Parkinson’s disease, the company said Tuesday.

The agency’s complete response letter (CRL) flagged observations discovered during an inspection of a third-party manufacturer listed in AbbVie’s drug application. The inspection at the facility did not involve ABBV-951 or any AbbVie medicine, the drugmaker stressed.

AbbVie’s prospective therapy is a combination of foscarbidopa and foslevodopa, which are the respective prodrugs for the carbidopa and levodopa included in AbbVie’s 2015-approved Parkinson’s treatment Duopa. Prodrugs are versions of medications that become active once they enter the body.

Despite the rejection, AbbVie remains committed to working with the FDA to bring ABBV-951 forward, Roopal Thakkar, M.D., SVP, and chief medical officer of global therapeutics at the company, said in a statement.

The FDA’s rebuff did not flag any issues related to the safety, efficacy or labeling of AbbVie’s drug candidate, including the combination’s subcutaneous pump device, which has caused problems for the drugmaker in the past.

Last March, ABBV-951 was rejected because the FDA needed additional information about the candidate’s delivery device.

ABBV-951, which analysts at Evercore ISI have hailed as one of AbbVie’s “biggest new product launches over the next year or two,” is designed to offer a convenience edge over the nearly decade-old Duopa, which comes in a gel form and must be administered orally with a pump through a stomach tube.

ABBV-951, for its part, is given continuously under the skin via a pump.

AbbVie added in its Tuesday press release that it’s not on the hook to run any additional efficacy or safety trials related to the drug candidate or its delivery device.

Previously, Wall Street analysts projected ABBV-951’s peak sales could reach $1 billion, though the Evercore team last year said it “wouldn’t be surprised” if the drug eventually surpassed the $2-billion mark.

Meanwhile, AbbVie’s prodrug Parkinson’s combo could eventually face competition in the form of Mitsubishi Tanabe Pharma’s ND-0612—also a continuous subcutaneous infusion but of liquid levodopa and carbidopa—which the Japanese company acquired in its $1.1-billion acquisition of NeuroDerm in 2017.

Thankfully for AbbVie, ND-0612 was also hit with a CRL earlier this month, Mitsubishi Tanabe revealed in a recent filing. Details on the rationale behind the rejection were slim, with the company simply noting that it would review the complete response and work with the FDA to address the regulator’s comments.

Elsewhere, infusion pump-based therapies have posed problems for other drugmakers developing Parkinson’s disease drugs, too.

Look no further than Supernus, which in April received a third rejection of its prospect SPN-830 tied to product quality and the drug’s infusion device master file.  

At the time, Supernus said it had submitted product quality data that the FDA had yet to review, adding that it planned to discuss requested information and steps to resubmit the master file for the delivery technology with the FDA. The rejection came after the FDA wrapped up a successful pre-approval inspection of the device manufacturer’s facility in February.

Supernus was not deterred and remains “committed to bringing SPN-830 to the market,” CEO Jack Khattar said in a statement earlier this year. “We will work with the FDA to address the CRL and to successfully resubmit our SPN-830 NDA.”