Memorandum

Intarcia’s ITCA 650 receives FDA Complete Response Letter – September 27, 2017

Executive Highlights

  • The FDA issued a Complete Response Letter (CRL) today for Intarcia’s GLP-1 agonist candidate ITCA 650 (implantable exenatide mini-pump). This is disappointing news, but according to the company announcement, no new pivotal trials or long-term activities will be required, and we’re keeping our fingers crossed for a swift resubmission.
  • Intarcia filed a 1.3 million-page New Drug Application (NDA) in November 2016, which was accepted for active review this past February. It’s unclear at this time whether the FDA’s concerns pertain to the continuous release of exenatide, to the Medici platform technology (implantable mini-pump, high temperature stability components, placement/removal kits), to human factors related to a drug/device combo, or to some other aspect of clinical data.

Intarcia announced today that the FDA has issued a Complete Response Letter (CRL) for ITCA 650, its implantable exenatide mini-pump providing continuous subcutaneous release of the GLP-1 agonist. The company submitted a New Drug Application (a whopping 1.3 million-page document) in November 2016, and the NDA was accepted for active review in February 2017. According to Intarcia’s announcement, management hopes to meet with FDA soon to discuss next steps, but the content of the CRL suggests that no new pivotal trials or long-term activities will be necessary. As we learned from CEO Mr. Kurt Graves when the drug candidate was filed, this was “not your typical NDA” – there were multiple, complicated pieces. The submission covered not only the pharmaceutical agent itself, but also the novel delivery device (Intarcia’s Medici platform technology including the implantable mini-pump, components that confer high temperature stability, and placement/removal kits for the implantable). Moreover, Mr. Graves alluded to a host of additional human factors that come into play when seeking approval for a drug/device combo. All this upped the NDA page count to 1.3 million. It’s unclear as of now whether the FDA’s concerns pertain to the continuous release of exenatide (the mini-pump works for three months in its initiation phase, and for six months in its maintenance phase), to the Medici technology, to human factors, or to some other aspect of clinical data (glycemic efficacy, CV outcomes, etc.). To be sure, there was a lot there that is new. We can’t overlook that ITCA 650 is unlike any other GLP-1 agonist already on the market, and FDA had its work cut out to thoroughly review all aspects of safety and efficacy. That said, the CRL still comes as disappointing news, and we’d certainly like to see a swift resubmission so that the number of people open to GLP-1 therapy continues to grow.

Since positive phase 3 results (first announced in October 2014), we’ve been keenly excited about the potential for ITCA 650 to bring innovation to the GLP-1 agonist class, and to grow the market as a whole by increasing uptake. The mini-pump reduces injection burden, often cited as a reason (one reason!) for low adherence to GLP-1 therapy. In turn, poor medication adherence leads to a gap between clinical trial results and real-world outcomes for people prescribed a GLP-1 agonist. ITCA 650 would circumvent the adherence issue entirely, offering a patient-friendly solution that should also pique payers’ interest.

Recent data presented at ADA 2017 (a post-hoc analysis of FREEDOM-1 and FREEDOM-2) showed how Intarcia’s candidate delays the need for other diabetes therapy. The phase 3 program found significant A1c-lowering and weight loss (which was sustained through at least nine months). FREEDOM-CVO found the exenatide mini-pump to be non-inferior vs. placebo on CV outcomes, and it’s important to note that this CVOT was designed to meet a safety endpoint in line with FDA’s 2008 guidance. There have even been rumors that the daily price of ITCA 650 would be less than that of once-daily injectable GLP-1 agonists.

Unfortunately, our pricing and reimbursement questions can now be pushed back, as we await more details on the CRL and Intarcia’s timeline for ITCA 650 resubmission. Interestingly, as a sidenote, Intarcia also won’t have to deal with PBMs, which could be a major advantage from multiple perspectives. Although that isn’t directly relevant to today’s news, it could well be quite noteworthy down the road.

  • Intarcia’s news release calls out the company’s strong financial position. More than $600 million have been raised through the current Series EE equity financing through September 2017, and just last week, the company added four new highly-respected board members in preparation for the “next stage of growth” – Dr. Jay Skyler, Dr. Patrick Conway, Mr. Jim Rosenthal, and former Nebraska Senator Mr. Bob Kerrey (read more about them here).

 

-- by Payal Marathe and Kelly Close