Failure to launch for 2010's big hopes

Having set out the hopes for the biggest and brightest product launches anticipated in 2010, it is time for EP Vantage to take a look at how they fared (Which of 2010's launches will be future blockbusters?, January 19, 2010). The answer is not particularly well – long-overdue approval for Amgen’s Prolia and Dendreon’s breakthrough with Provenge were more than offset by regulatory delays and rejections to the likes of AstraZeneca’s motavizumab and Certriad.

Of the 20 biggest biotech and conventional products that analysts expected to reach the market last year, just eight managed to make it compared to ten successes in 2009 (Failure to launch for 2009’s big hopes, January 15, 2010). The year was not great for big pharma either, involved in just four of the product lift-offs in 2010. As such, forecast sales for the product class of 2010 have been reduced by 25% with over $5bn wiped off estimates for 2014 (see table below).

Lift off

In general terms, biotech products fared better than more conventional drugs. Five of the eight launches were biotech agents, with Provenge the runaway success as the industry’s first approval of a cancer vaccine (Relief all round as Dendreon bags landmark Provenge approval, April 30, 2010).

So far demand for Provenge has outstripped supply and Dendreon is predicting a tenfold increase in manufacturing capacity through 2011. As such, sales of Provenge in 2010 at $45m are expected to rapidly increase with consensus estimates for 2014 doubling to $2.16bn; revenues could even exceed $3bn by 2016.

Of the other big biotech launches last year, Prolia and Pfizer’s pneumococcal vaccine, Prevnar 13, were much more predictable. Prolia had been slated for launch in 2009, but finally won approval in June as a treatment for post menopausal osteoporosis (Amgen gets early surprise from FDA with Prolia approval, June 2, 2010). Subsequent approval for reducing skeletal-related events (SREs) in certain cancer types and encouraging data for preventing bone metastases suggest Amgen has a multi-billion dollar product in its hands (Amgen data confirms Xgeva potential, December 14, 2010).

Although Prevnar 13 is essentially just an extension of an existing franchise – a 13-valent vaccine compared to the older 7-valent Prevnar introduced by Wyeth ten years ago – approval and launch last year was critical for Pfizer; the vaccine is now the pharma giant’s most valuable product with an NPV of $18.6bn (With US backing Prevnar 13 aims for blockbuster status, February 25, 2010).

Last year’s approval and launch for Savient’s gout drug (Krystexxa), Acorda’s MS agent (Ampyra), and Auxilium’s Dupuytren's contracture therapy (Xiaflex), were all hugely important as the first commercial products to emerge from their respective pipelines.

Meanwhile the launch and rapid uptake of Shire’s Gaucher’s agent, Vpriv, was an added bonus for the UK specialty group given Genzyme’s manufacturing problems which are significantly limiting its capacity to produce Cerezyme.

Damp squibs

Of the products that failed to reach the market last year, causes for the setbacks range from modest regulatory delays to outright rejection, resulting in some companies ditching all further development.

Perhaps the biggest single disappointment was the failure of Amylin, Eli Lilly and Alkermes’ anti-diabetic Bydureon, hitting the shares in all three partners (FDA crashes party of three with Bydureon rejection, October 20, 2010). Somewhat surprisingly the FDA requested more cardiovascular safety data on the once-weekly product which was supposed to build on Byetta’s success as a twice-daily therapy. Approval for Bydureon is now anticipated in 2012, significant delay giving Novo Nordisk’s once-daily agent Victoza more time to eat into Byetta’s market share.

Unfortunately for AstraZeneca it was involved in a couple of significant setbacks in 2010.

Its drug for the prevention of respiratory syncytial virus infection motavizumab (formerly Numax) was discontinued after a second complete response from the FDA in September (Second motavizumab complete response could make AstraZeneca think twice, September 1, 2010); archived forecasts for 2016 sales dropped dramatically from $930m in August to $112m in December. It is still being developed as a non-prophylactic – a phase II trial will complete this month. However a much smaller target population will not bring big financial reward (AstraZeneca scales back motavizumab, December 21, 2010).

AstraZeneca also dropped development of mixed dyslipidemia drug Certriad in December, following March’s rejection by the FDA. The company and its partner Abbott Laboratories decided that the delay and competition from generic combinations of statins and fenofibrates meant the product was not financially viable (Astra pulls plug on Certriad, December 23, 2010).

Development of Comfyde, Johnson & Johnson’s anti-epileptic was dropped for the epilepsy indication, having received a complete response from the FDA in August 2009. Phase II trials in diabetic neuropathy continue, but the loss of its primary indication sent 2014 sales consensus down from $472m in January to just $97m by September.

Human Genome Sciences and Novartis’ hepatitis C interferon drug, Zalbin, filed in late 2009, was also scrapped after negative opinion on the risk/benefit profile from both FDA and EMA in October.

The regulator also requested new trials in a complete response in April to Cell Therapeutics, for non-Hodgkin’s lymphoma candidate Pixuvri (pixantrone; BBR 2778), not satisfied by the scope of pivotal data that were submitted (FDA makes quick work of Pixuvri, April 12, 2010). As a result, archived forecasts diminished to a tenth of their value; in February 2010 consensus was $647m for 2016 global sales, in June it was $68m. New data showing overall survival benefit raised hopes once again in June, and an FDA decision is expected this quarter. Furthermore the EMA accepted a marketing application in November and a decision is now expected next quarter.

Delays

One of 2010’s biggest would-be approvals, MannKind’s inhaled insulin Afrezza, was delayed by four weeks in December, in order for the FDA to conduct further reviews. Shares in MannKind rose as many were expecting an outright rejection. Analysts were at odds though, some confident of a January approval, while others doubtful the FDA was convinced by the data submitted (Clinical and regulatory events over the Christmas period, January 4, 2011).

GlaxoSmithKline and Human Genome Sciences’ lupus drug Benlysta was delayed beyond its December PDUFA, with the FDA expected to make a decision on March 10, 2011. Commercial restrictions are expected after Benlysta brought questionable efficacy in some patient groups (Benlysta wins adcom backing but questions remain over potential, November 17, 2010).

Meanwhile the FDA requested additional time to review Merck KGaA’s oral MS therapy Movectro (cladribine), seen as the biggest competitor to Novartis' Gilenya. A decision is expected at the end of February. The pill was rejected in Europe in September after an advisory board felt benefits did not outweigh its risks, although did win approval in Russia and Australia during 2010 (Negative EU vote on cladribine leaves Gilenya strolling to the finish line, September 24, 2010).

Cadence’s injectable formulation of acetaminophen, Ofirmev, almost made it over the finishing line in 2010. Manufacturing deficiencies identified in a complete response letter in February were resolved and FDA approval was granted in November (Market marches to different beat following Cadence approval, November 3, 2010). The company plans to roll out the product in the first quarter this year.

Lastly InterMune’s Esbriet (pirfenidone) had a rollercoaster year. It was rejected in the US in May, with requests for an additional trial, as archived forecasts plummeted from $1.3bn in 2016 sales in April to $63m by June (InterMune left gasping by FDA rejection of pirfenidone, May 5, 2010). Esbriet nevertheless received European approval in December 2010, sending the company’s stock skyrocketing as multiple analysts upgraded their ratings (InterMune receives welcome European approval gift for Esbriet, December 20, 2010).

Notable others

While the picture painted above is not a particularly bright one, it is worth noting a couple of products which are not included in this list but their success redresses the negative balance somewhat.

Novartis’ oral MS pill, Gilenya, was undoubtedly one of the stand-out approvals last year, its surprisingly rapid FDA approval surpassing expectations with sales now projected to reach $2.5bn by 2016. Gilenya does not appear in the analysis above because a year ago sales estimates were much more modest and a launch had not been slated until early 2011 (Novartis wins strong label for first oral MS pill, September 22, 2010).

Novo Nordisk’s diabetes agent, Victoza, does not appear in this list either because it had already gained approval in Europe in 2009. However, a somewhat surprising FDA approval in January 2010 has led significant upgrades to forecasts which now stand at $1.4bn by 2016 (Victoza's victory could be short lived, January 26, 2010).

As such, the product class of 2010 was far from outstanding but largely in keeping with success rates in prior years.