#1: F. Hoffman-La Roche

Headcount                   80,653

Year Established        1896

Pharma Revenues     $35,629        -1%/-5%*

Total Revenues          $45,643         1%/-3%*

Net Income                  $8,548            9%/4%*

R&D Budget                $7,845          -5%/-8%*
 

* Converted at avg. exch. rate / based on reported currency (EUR)

Top-Selling Drugs in 2010

Account for 77% of total biopharma sales, same as in 2009.

PROFILE

A funny thing happened on the way to the top. Just 18 months ago, Roche’s Avastin was on the march to becoming the world’s top-selling drug. A few failed trials and regulator/payor restrictions later, and Avastin wound up posting a 5% decline in 4Q10 and a 6% drop in 1Q11. Now it’s not even the top-selling drug at Roche! (That honor went to Rituxan in 1Q11.)

It began with a missed endpoint in a Phase III trial in prostate cancer in March 2010 (noted in last year’s report, a long with failures in stomach and early colorectal cancers). Then the big shoe dropped in July 2010 when an FDA advisory panel questioned Avastin’s effectiveness as a breast cancer treatment. The panel voted 12-1 against keeping that indication for the drug, and the FDA followed its suggestion in December 2010.

Avastin had received accelerated approval for Avastin in breast cancer in 2008, but the FDA cited several trials that showed Avastin failed to prolong overall survival in breast cancer patients or slow down the disease enough relative to the risks of Avastin’s side effects. It’s not the first time that a drug with accelerated approval ended up losing that indication, but it’s certainly the most high profile one.

Roche, naturally, appealed the FDA’s ruling. So while the rest of the biotech industry was gathered in Washington DC in late June for the BIO conference, Roche executives were at the FDA’s White Oak Campus in Silver Spring to argue for Avastin’s reinstatement as a breast cancer treatment. The FDA’s ban is pending the outcome of the hearing process, but if it’s upheld, it could lead to a $1 billion drop in Avastin revenues. (The EMA still considers Avastin beneficial against breast cancer.) (UPDATE: The FDA upheld its ruling.)

Meanwhile, the UK’s NICE considers Avastin too expensive for colorectal cancer treatment, given the benefits (six extra weeks of life, on average). Roche tried developing a new patient access scheme, but was rejected by the inaptly named institute. 

Oh, and Roche is still battling to keep pharmacists from giving patients Avastin instead of Lucentis for wet macular degeneration, going so far as to highlight the higher death rate in patients treated with Avastin instead of Lucentis for that indication. 

What does all this mean? Well, Roche has revised its peak sales estimates of Avastin from $8.7 billion to around $6.7 billion and, given that it posted $6.2 billion in 2010 sales, that may mean this is as good as it gets. That’s an awfully big number, but Roche was expecting a lot more from the Avastin engine when it acquired Genentech in 2008. (And Avastin did just post good results against ovarian cancer, so there’s still a potential for growth.)

But enough about Avastin. What else is going on at our Top Biopharma company? In last year’s report, Tamiflu posted the biggest single-year revenue gain of any drug we covered, driven by H1N1 pandemic influenza stockpiling. This time around, it posted the biggest drop in revenues, losing $2.1 billion in revenues. (The next largest loss came from Merck’s Cozaar/Hyzaar hypertension drug, which shed $1.5 billion after losing patent protection.)

This year didn’t start well for Roche, either. The pharma division posted a 10% drop in revenues (in CHF) in 1Q11, although a huge currency flux made those numbers look good in dollars. Even if you exclude the trailing sales of Tamiflu, Roche Pharma dropped 8% in the quarter.

These declines, combined with some serious pipeline problems (as well as pricing pressures in Europe and healthcare reform dues in the U.S.), led Roche to break out the old Operation Axe-cellence (whoops! I meant “Excellence”). Following up on 2009’s restructuring and layoffs, Roche in September 2010 announced that it was reviewing operations. By November, it had decided that 4,800 jobs will be cut, 800 will be transferred and 700 will be outsourced, and more facilities will be shut down or consolidated. The company plans to cut, transfer or outsource the jobs of 2,650 people from sales and marketing, 1,350 from manufacturing, 800 from product development, 600 from research and early development, 640 from diagnostics and 260 from back-office functions. This latest round of cuts is designed to yield $2.4 billion in annual savings, but will cost $3.2 billion to implement, continuing through the end of 2012. There were R&D cuts, including the decision to cancel all RNA interference programs, but no talk of merging Roche and Genentech’s early R&D units.

As I wrote, the restructuring wasn’t just the result of Avastin restrictions and no Tamiflu sales. Roche has had some late-stage pipeline problems, too. The Phase III trial of GLP-1 diabetes treatment taspoglutide was called off due to a high rate of gastrointestinal reactions. Roche cancelled the trial in September 2010 and returned rights to partner Ipsen in February 2011. At one point, taspoglutide had peak annual sales estimates of $2.0 billion.

In August 2010, the FDA issued a Refuse To File letter for the accelerated BLA of Herceptin-followup T-DM1. The agency contended that the Phase II trials of T-DM1 that formed the basis of the BLA “did not meet the standard for accelerated approval because all available treatment choices approved for metastatic breast cancer, regardless of HER2 status, had not been exhausted in the study population,” according to a Roche statement. The company is continuing its Phase III trial and expects to re-file in mid-2012.

That said, Roche has around a dozen NMEs in Phase IIb or III, half of which have accompanying diagnostic tests for personalized medicine applications. At the recent ASCO meeting, Roche made a splash with vemurafenib, a melanoma treatment that reduced risk of dying by a mind-blowing 63% in one trial. In June 2011, Roche joined forces with Bristol-Myers Squibb to put vemurafenib in dual treatment with BMS’ recently approved Yervoy, to put a double-whammy on melanoma in certain genomically-defined patient populations. In all, the company hopes to make as many as 10 new drug submissions by the end of 2013.

More than double the size of the #2 biopharma, Roche is in no danger of losing the top spot in our ranks. However, the company has a tough road ahead. Its products are effective but expensive, making them lightning-rods in the new age of payor-austerity. Also, the threat of biosimilars is still years ahead: Avastin is protected until 2018, by most standards, but Herceptin and Mabthera have patent expiries in Europe in 2014 and 2015, respectively. If Roche doesn’t get its next generation of bio-blockbusters on the market, it could be looking at a long, slow decline. (Or, of course, a mega-merger.)  —GYR
 

THE LOWE DOWN

The verdict on the merger? So far, so pretty good, at least from the outside. It’s created the biggest oncology company in the world, thanks to Avastin. And no matter how big the company is, Avastin is so big by itself that, for some time to come, it’ll be the biggest factor in how people see the whole company. Oncology being the ever-fragmented field it is, there always seem to be more patient populations and treatment combinations to add some Avastin to, which generates a steady supply of news for the analysts. Works in another indication? Things are good. Provisional approval being rolled back? Things aren’t so good.

That’s sort of a shame, since they have a lot of other things going on, including a nearly J&J-like number of outside collaborations. But there are worse problems than having lots of attention paid to your huge-selling cancer drug, as many other companies can demonstrate.

Of course, Roche (like everyone else) has had its pipeline problems and its rounds of layoffs. But overall, between these folks and Novartis, the Swiss pharma industry is looking pretty respectable these days. —Derek Lowe
 

ACQUISITION NEWS

Target: Marcadia Biotech

Price: $287 million, plus $250 million in potential milestones

Announced: December 2010

What they said: Pretty much nothing. The company put out no press release about the purchase and only revealed the price two months later. In its annual report, the company noted, “In December Roche acquired Marcadia Biotech, a privately owned U.S. company focusing on the development of innovative therapeutics for metabolic diseases. Marcadia’s research and development programs on new peptide therapies for the treatment of type-2 diabetes and obesity will be integrated into Roche’s R&D portfolio. These include next generation peptides such as MAR701, currently in Phase I development for type-2 diabetes.”

On the diagnostic side of the business (which, admittedly, is growing ever more intertwined with the drug side, much to my chagrin), Roche acquired BioImagene in August 2010 for $100 million in cash. BioImagene is a provider of digital pathology laboratory solutions, creating high-res, whole-slide digital images from glass microscope slides.

In March 2011, Roche bought PVT, for approximately $90 million, plus $38 million in milestones. PVT’s product portfolio covers automation of pre- and post-analytical tasks, such as centrifuging, pipetting, sorting and archiving across a large variety of sample formats. The company’s products “enable clinical laboratories to reliably manage low to very high sample volumes and to arrange their lab space with great flexibility,” according to a Roche statement.
 

OUTSOURCING NEWS

With its November 2010 Operational Excellence restructuring announcement, Roche noted that it would transfer or outsource 1,500 jobs, in addition to 4,800 layoffs. It appears that the outsourcing activity involves sales reps, with several reports indicating that Tamiflu’s sales would be conducted by a contract sales organization.

In September 2010, Argenta extended its small molecule discovery outsourcing collaboration with Roche unit Genentech. The agreement permitted Genentech to place projects with Argenta’s sister division, BioFocus. That division provides integrated medicinal chemistry, in vitro biology and ADME services. Argenta and Genentech began working together in 2005, with Argenta providing computer-aided drug design and other services to screen NCEs against Genentech-defined targets. Both Argenta and BioFocus are owned by Galapagos NV. 

Next Profile: Amgen