Memorandum

FDA approves J&J’s Invokamet XR (canagliflozin/metformin extended-release) – September 22, 2016

Executive Highlights

  • The FDA has approved J&J’s Invokamet XR, a once-daily formulation of Invokana (canagliflozin) and extended-release metformin.
  • Invokamet XR will hold an indication for first-line therapy in adults with type 2 diabetes, and will be available in pharmacies as early as next week (September 28).
  • We spoke with J&J’s VP of Medical Affairs Dr. Paul Burton about how Invokamet XR “rounds out” the company’s Invokana franchise and offers flexibility to patients and providers.

Earlier this week, J&J announced the FDA approval of its extended-release combination product Invokamet XR (canagliflozin/metformin XR). The once-daily formulation is indicated as first-line adjunct therapy to diet and exercise for adults with type 2 diabetes. This decision arrives the expected 10 months after the company submitted the XR version of Invokamet to the FDA. The product’s approval follows that of the twice-daily formulation of Invokamet, which was approved in 2014 and which received an expanded first-line therapy indication in May 2016.

As emphasized in J&J’s announcement, and by VP of Medical Affairs Dr. Paul Burton in a separate conversation we had with him, once-daily dosing of Invokamet affords busy patients and providers much-needed flexibility and convenience. To this end, we’re enthusiastic about the availability of SGLT-2 inhibitor/metformin XR combinations as first-line diabetes treatment options. The recent announcement further emphasized that the first-line indication for Invokamet XR aligns with current AACE/ACE and ADA/EASD guidelines, which recommend dual therapy for patients with A1c >7.5% after three months on metformin monotherapy and for patients with A1c >9% right off the bat. Indeed, Dr. Burton emphasized that Invokamet XR might be most advantageous for patients with A1c >9% who are having difficulty reaching target. He added that “the more great medicines there are available, the better things are for patients,” and we couldn’t agree more. The introduction of Invokamet XR in the US is terrific news, and we’re excited to see this product benefiting patients as early as next week – it hits pharmacies September 28.

  • Dr. Burton suggested that Invokamet XR’s availability in four doses makes the product an attractive option for healthcare providers by offering the flexibility to prescribe the drug to a wide spectrum of patients. Invokamet XR will be available in four tablets: (i) 50 mg canagliflozin/500 mg metformin XR; (ii) 50 mg canagliflozin/1,000 mg metformin XR; (iii) 150 mg canagliflozin/500 mg metformin XR; and (iv) 150 mg canagliflozin/1,000 mg metformin XR. The recommended dosing is two tablets once-daily, whereas regular Invokamet is dosed as one tablet twice-daily. As a result, Invokamet XR wouldn’t necessarily reduce pill burden, but may help improve adherence in that patients will only need to remember to take the medication once a day rather than twice. For comparison, AZ’s Xigduo XR (dapagliflozin/metformin extended-release) is available in five doses, four of which involve one tablet once-daily while the largest dose is split into two tablets. We’re curious if the higher quantities of canagliflozin molecule required to achieve similar efficacy as dapagliflozin may play a role in the need for two tablet dosing with Invokamet XR – Xigduo XR formulations only contain either 5 mg or 10 mg of dapagliflozin (combined with 500 mg, 1000 mg, or 2000 mg of metformin XR) compared to the 50 mg or 150 mg doses of canagliflozin in Invokamet XR. Given this difference in dose administration, we’re eager to see how Lilly/BI’s SGLT-2 inhibitor/metformin XR formulation Synjardy XR (empagliflozin/metformin extended-release) will be dosed.
  • Though exact pricing on Invokamet XR is still unknown, Dr. Burton remarked that the company’s goal is to price the drug “on par with Invokana.” We’re glad to hear that Invokamet XR won’t be priced at a significant premium over Invokana. Given the low cost of metformin, we imagine patients on Invokana would have had to make tough choices between affordability or convenience if Invokamet XR were priced as a significant premium to separate Invokana and metformin therapy. We’ll be curious to see how Invokamet XR is positioned on formularies relative to Xigduo XR, and how the approval of Synjardy XR next year shakes things up further. Notably, J&J’s Invokana franchise remains the frontrunner in the SGLT-2 inhibitor market in sales and prescription volume, largely due to its first-to-market position in the US, which generally accounts for the bulk of diabetes drug revenue worldwide. Outside of the US, AZ’s Farxiga franchise launched first and enjoys greater access and sales as a result.
  • Invokamet XR will now be the second SGLT-2 inhibitor/metformin XR product to hit the US market. AZ’s Xigduo XR was previously launched in the US after an October 2014 FDA-approval. An FDA decision for Lilly/BI’s Synjardy XR is expected by 1Q17. Across the pond, AZ’s twice-daily Xigduo was first-to-market in Europe, followed by J&J’s twice-daily combination in this class, called Vokanamet in the EU. Lilly/BI’s twice-daily formulation of Synjardy joined European markets one year later, in May 2015. Extended-release metformin is not yet commercially available in Europe, which hinders the availability of once-daily combination tablets of an SGLT-2 inhibitor with metformin.
  • “The approval of Invokamet XR rounds out much of the research and development we’ve done with canagliflozin and Invokana.” Dr. Burton shared his view that the recent FDA decision adds an important piece to the Invokana franchise. We look forward to hearing additional commentary from J&J on Invokamet XR during its 3Q16 earnings update (slated for October 18). We’ll be watching to see how this once-daily tablet affects sales for the company’s Invokana (canagliflozin) franchise overall.

 

-- by Payal Marathe, Helen Gao, and Kelly Close