Welcome to your weekly digest of approaching regulatory and clinical readouts. In the run-up to Christmas, next week will be busy for the FDA’s advisory committees. Bristol-Myers Squibb/AstraZeneca's lipodystrophy project metreleptin will be discussed on December 11 and a panel on Forxiga, their diabetes candidate, is scheduled for the following day.
In a small study metreleptin produced encouraging results treating metabolic disorders associated with lipodystrophy, a rare disorder. Since the only approved drug is indicated for HIV-associated disease, metreleptin could dominate this niche market. The companies will hope that the SGLT-2 inhibitor Forxiga will finally see a smooth path to market after receiving a complete response letter in January over potential cancer imbalances.
Bristol and Astra are seeking to have metreleptin indicated for treating metabolic disorders such as diabetes or hypertriglyceridemia associated with inherited or acquired lipodystrophy, which is characterised by a loss of adipose tissue and an accumulation of fat in the blood or around organs (Lipodystrophy could give metreleptin a new lease of life, May 7, 2013).
Patients also lack circulating leptin, a hormone that regulates energy intake and expenditure. Metreleptin has orphan drug status in the US and EU, and was given US priority review status, but in July the FDA announced that a three-month extension was needed, giving a PDUFA of February 24 2014. Japanese approval came earlier this year.
Subgroup analysis from a small NIH study showed that, in 15 patients aged between 12 and 18, 12 months’ metreleptin caused statistically significant reductions in HbA1c and triglyceride levels. Metreleptin was initially being developed for obesity in combination with pramlintide, but this work was discontinued in 2011, and its originator, Amylin, was bought last year jointly by Bristol and Astra for $7bn.
Merck KGaA’s Egrifta (tesamorelin) is the only marketed product for lipodystrophy, but is indicated for the reduction of excess abdominal fat in HIV-infected patients. Last year sales were $23m. Leerink Swann analysts note that, with limited options for inherited or acquired lipodystrophy, sales of metreleptin could reach $100m by 2018, with JP Morgan forecasting $300m peak revenue.
Astra and Bristol will have their fingers firmly crossed again when Forxiga (dapagliflozin) comes under scrutiny in the US for the second time. Risks of elevated genitourinary infections with the SGLT-2 class are well known, but Forxiga fell on reports of an imbalance in breast and bladder cancers disclosed just weeks leading up to its first panel. The setback allowed Johnson & Johnson’s Invokana (canagliflozin) to become the first SGLT-2 to the US market when it was approved earlier this year (Adcom backing gives canagliflozin a chance at an open diabetes field, January 11, 2013).
After the complete response letter Bristol submitted new studies and additional long-term data. Results at EASD showed that 31.8% of patients taking 10mg Forxiga achieved goal HbA1c levels of less than 7%, versus 11.1% of patients on placebo at week 24, with a p value of <0.0001. 48.6% of patients taking Forxiga and 51.4% of those on placebo experienced adverse events, most of which were mild or moderate.
Forxiga's PDUFA date is set for January 11, and according to EvaluatePharma 2018 sales could reach $805m, with Invokana forecast at $1.1bn. The diabetes market is becoming crowded, and another SGLT-2 is hot on the heels of Forxiga: Boehringer and Lilly’s empagliflozin has an FDA action date at the end of January and an advisory meeting has not been disclosed. 2018 sales are forecast at $650m.
Despite the US setbacks, Forxiga was first to market in Europe after being approved in November 2012. This and the subsequent US approval of Invokana could suggest that safety fears of the class have been allayed.
American Society of Hematology
This year’s ASH meeting is taking place on December 7-10 in New Orleans, and our reporter Jacob Plieth will be attending. Follow @JacobEPVantage on Twitter for live updates (ASH preview – The industry’s next test of a post-Jakafi world, Nov 8, 2013).