Adcom backing gives canagliflozin a chance at an open diabetes field

Johnson & Johnson’s diabetes pill canagliflozin has stepped a little closer to becoming the first drug in its class to reach the US market. A positive FDA advisory committee vote signals that diabetes specialists are growing comfortable with the safety profile of its class, which include Forxiga and the phase III candidate empagliflozin.

With a 10-5 vote in favour of approval, canagliflozin just hit the two-thirds “yes” vote threshold that seems to be a surest route to quick approval. FDA approval by the March action deadline is not a certainty, of course, but things are looking up for both the drug and the class; first-mover advantage is shifting to J&J.

Risk management

Some risks of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor class are well known and have been well defined. The inhibitors block reabsorption of glucose in the kidneys and thus increase urinary glucose excretion; this in turn leads to elevated genitourinary infections.

AstraZeneca and Bristol-Myers Squibb’s Forxiga, known generically as dapagliflozin, fell in the US on an imbalance of breast and bladder cancers, although it has received European Union endorsement (Event – J&J hopes canagliflozin flourishes where Forxiga failed, January 4, 2013). Thus, the FDA staff’s view on canagliflozin’s safety was eagerly awaited.

In briefing documents released before the adcom meeting, FDA staff noted elevated risks of cardiovascular events in the first 30 days of treatment in a dedicated safety trial, along with renal events. Because of the SGLT-2 mechanism of action, strict labelling to address renal safety issues was always likely, and the expert panellists’ debate confirmed that likelihood.

The cardiovascular trial is still ongoing, and thus full data might answer the question about how great the risk actually is; analysts from UBS said the integrity of that trial could be under threat if canagliflozin, which has the proposed trade name Invokana, is approved as enrolees might be tempted to drop out in order to be sure of being prescribed the drug. Thus an additional cardiovascular safety trial could be a condition of approval.

Reading tea leaves

Getting a first US approval in the SGLT-2 class would be a good sign for Astra and Bristol-Myers, not to mention the pairing of Eli Lilly and Boehringer Ingelheim. The latter two reported positive topline phase III data for their SGLT-2, empagliflozin, earlier this week, putting it on a solid track toward submission this year (Lilly diabetes risk-sharing starts to unwind as Boehringer pulls back, January 8, 2013).

Forxiga’s fate seemed to be sealed by poorly timed disclosure of the cancer imbalance in the last weeks leading up to its adcom. EU approval suggests that at least some of the immediate fears have been allayed in the regulatory community; a US resubmission with new data is expected in 2013.

Meanwhile, empagliflozin’s prospects will become much clearer once the US and German partners disclose data at the American Diabetes Association meeting later in the year.

The entire class is forecast to generate about $2bn in sales in 2018, with canagliflozin accounting for $900m, according to EvaluatePharma data – seemingly a healthy amount until it is compared to the glucagon-like peptide-1 agonist Victoza, which is forecast to generate $2bn alone in 2013, only its fifth year on the market.

One of the reasons the SGLT-2 class is not expected to be so robust is that with much diabetes prescribing in the hands of primary care practitioners, the well-documented urinary complications become an additional patient management worry. Still, another product that can help keep patients from advancing to insulin treatment would be a welcome addition.

Thus there will be quite a few crossed fingers in big pharma executive suites as the canagliflozin decision nears  most of all at the New Jersey headquarters of J&J, which could get about a year’s head-start in a novel class that promises a blockbuster opportunity.

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @JonEPVantage on Twitter

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