Takeda’s ARB approved to a muted reaction
While Takeda sounded off over securing FDA approval for blood pressure pill Edarbi (TAK-491), it seems investors have held back the fanfare. Approval of the Japanese company’s second-biggest sales growth driver over the next six years was met with a muted market reaction - the stock gained just 1% to ¥4,065 - perhaps reflecting uncertainty over the drug's commercial potential (Event - Takeda's ARB may be approvable but commercial potential uncertain, February 4, 2011).
The once-daily angiotensin II receptor blocker (ARB) enters an increasingly genericised and competitive market, making for a tricky promotional effort which will have to draw heavily on some decent head-to-head clinical data against the current ARB incumbents, Diovan and Benicar. As such, analysts are divided over how well Edarbi will sell, with forecasts for 2015 ranging from $273m to $738m; in contrast, Diovan and Benicar achieved sales last year of $6.1bn and $2.9bn, respectively.
At a dose of 80mg/day, Edarbi, generically known as azilsartan medoxomil, was significantly better during pivotal trials at lowering blood pressure over a 24-hour period than the highest doses of Novartis' Diovan and Daiichi Sankyo's Benicar. Meanwhile, side effects including the most common – diarrhoea – were manageable.
The regulator issued a restrictive ‘boxed’ label warning, albeit only to recommend against use by pregnant women. Given that all drugs affecting the renin-angiotensin system can be fatally damaging to a developing foetus, this warning is not surprising.
Added to the label was a further note to monitor patients with renal impairment, as renin-angiotensin-modulating drugs have been implicated in blocking urinary function, causing abnormal build-up of nitrogen-based waste compounds, and with renal failure on rare occasions.
Forecasts mark varying opinion
EvaluatePharma’s consensus for Edarbi, taken prior to this approval, stood at $572m in 2015 global sales, rising to $717m the following year.
While these figures are not a patch on Takeda's current ARB blockbuster Blopress, which generated global sales last year of $3.2bn, more telling perhaps are the banks’ broadly different predictions of Edarbi’s commercial potential.
Exceeding most forecasts is Nomura which sees $738m in 2015 sales. Barclays Capital is less optimistic, pencilling in $409m, while at the bottom of the scale sit Deutsche Bank with $300m, and Bank of America-Merrill Lynch slightly lower still at $273m.
Takeda’s pipeline is under considerable pressure to deliver with the loss of patent protection on multi-billion dollar franchises.
Blopress loses US patent protection next year, sold as Atacand by global partner AstraZeneca, while Takeda desperately needs to plug the hole that will be left by $4.3bn-selling anti-diabetic Actos when it loses patent protection, also in 2012.
A follow-on DPP-IV inhibitor anti-diabetic, Nesina, should be filed in the US over the course of this year. As Takeda’s biggest potential growth driver – launched in Japan last June – Nesina could yet breach the $2bn barrier by 2016.
Meanwhile analysts at Bank of America-Merrill Lynch wrote earlier in the month that they expect Takeda to make a major M&A announcement prior to Actos’ patent expiry, to offset some of these losses to revenues and profits.
Edarbi has undoubtedly impressed in the clinic as a worthy successor to Blopress, and could similarly see approval in Europe mid-year. However, with generic ARBs of Diovan, Blopress and Bristol-Myers Squibb's Avapro poised to flood the market over the next 18 months, purely on cost alone it is hard to imagine large numbers of patients and payers opting for a branded alternative.
As such, Edarbi's potential is most likely to be found as an alternative therapy for patients failing other ARBs, which still remains an unmet need and appears to be the main thesis for the FDA sanctioning the drug's use.
As Dr Norman Stockbridge, director of the Division of Cardiovascular and Renal Drugs Products at the FDA Center for Drug Evaluation and Research, put it: “High blood pressure remains inadequately controlled in many people diagnosed with the condition, so having a variety of treatment options is important.”