Personalized medicine, which targets individualized treatment and care based on personal and genetic variations, holds much promise for the pharmaceutical industry. Several pharmaceutical majors continue to invest in this emerging field as evident by Roche’s $5.7-billion bid last week for Illumina, a provider of gene-sequencing tools and related analytics.

Roche, perhaps, more than any other pharmaceutical company, is banking heavily on the combination of diagnostics and drug development to drive pharmaceutical innovation. In reporting its 2010 results in February 2011, Roche reported that it had 12 new molecular entities in late-stage development, of which six were potential personalized healthcare medicines with planned companion diagnostic tests, which included Zelboraf (vemurafenib) and its companion diagnostic for BRAF mutation-positive metastatic melanoma. FDA approved Zelboraf for treating BRAF V600E mutation-positive, inoperable, or metastatic melanoma and the cobas 4800 BRAF V600 Mutation Test, a diagnostic test developed by Roche, in August 2011.

Earlier this month, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended that Zelboraf be granted full marketing authorization as a monotherapy for treating adult patients with BRAF V600 mutation-positive unresectable or metastatic melanom. The corresponding European Commission decision on the marketing authorization of Zelboraf is expected in February 2012. Marketing authorization submissions for Zelboraf also are under review by health authorities in Australia, New Zealand, Brazil, India, Mexico, Canada, and other countries worldwide.

Roche also is using its diagnostic strategy to support new indications for existing drugs. Last month, it reported that the cobas EGFR Mutation Test was CE-marked, an indicator of a product’s conformity with EU requirements, and is now commercially availabile in Europe and other countries that recognize the CE mark. The cobas EGFR Mutation Test is a companion diagnostic to identify patients with non-small-cell lung cancer (NSCLC) who harbor mutations in the EGFR (epidermal growth factor receptor) gene and who may benefit from treatment with anti-EGFR tyrosine kinase inhibitors, such as Roche’ Tarceva (erlotinib). Tarceva, an oral EGFR inhibitor, was first approved in September 2004 to treat locally advanced or metastatic NSCLC after failure of at least one other chemotherapy treatment. It later was approved by the European Commission in September 2011 as a first-line monotherapy in people with locally advanced or metastatic NSCLC with EGFR-activating mutations.

Other companies also are reporting success with certain personalized medicines. In August 2011, FDA approved Pfizer’s Xalkori (crizotinib) for treating locally advanced or metastatic NSCLC that expresses the abnormal anaplastic lymphoma kinase (ALK) as detected by an FDA-approved test. The agency approved the drug along with a diagnostic test for the ALK gene abnormality, Abbott Molecular’s Vysis ALK Break Apart FISH Probe Kit. Up to 7% of those patients with NSCLC, typically patients without a history of smoking, have the gene abnormality.

Although personalized medicines will likely hold only a small part of the overall pharmaceutical market by value and volume in the near term, these successes portend of a changing paradigm in drug development.

A magazine ad for Boniva, fronted by actor Sally Field, generated the DDMAC (now the Office of Prescription Drug Promotion, or OPDP) Untitled Letter last year due to following phrase: “After one year on Boniva, 9 out of 10 women stopped and reversed their bone loss.” That didn’t jibe with the scientific data, DDMAC said in the letter, before requesting that all ads containing the phrase be removed from the campaign.

Genentech went a step further. In September of last year, the company began running corrective magazine ads addressing the overstated claim. The corrective ad states that the violative ad “may have given you the wrong impression.” It goes on to state that “Boniva has not been proven to stop and reverse bone loss in 9 out of 10 women and is not a cure for postmenopausal osteoporosis.” The corrective ads will run though April 2012.

Unlike their mild-mannered, Untitled Letter cousins, Warning Letters are considered more severe, and they typically mandate corrective ads to clear up any overstated claims or minimized risk information. Given that Genentech received the former communique and not the latter, it’s notable that the company chose to run corrective ads without a mandate.

After speaking with DDMAC about the Untitled Letter, Genentech worked with the agency to create and then “voluntarily” launch the corrective ads last September, according to Chris Vancheri, director, public affairs, at Genentech.

In a statement, Genentech said that in addition to the corrective advertisements – which are running in several women’s magazines, including Weight Watchers and this month’s WebMD the Magazine – “our clinical specialists have reached out to health care providers” to inform them about the corrective ads, which intend to “clarify the benefits and risks of Boniva in women suffering from post-menopausal osteoporosis.”

Sally Field was the face of Boniva beginning in 2006, but Vancheri says Field is “no longer engaged” on the campaign. GlaxoSmithKline signed a co-promotion deal with Roche on Boniva in 2001, but the companies broke the partnership in 2010.

On Friday Roche confirmed it had come to the end of its tether with state-funded hospitals in Greece. In an interview with the Wall Street Journal, CEO Severin Schwan announced that the company has increased shipments of drugs to pharmacies in the country, while cutting off supply to those Greek hospitals that have failed to pay their drugs bills or have paid them in government bonds. Roche has been stung by Greek bonds before, having had to sell a recent batch at a 26% discount. Further, if Greece defaults on its euro debt its government bonds would be rendered worthless. Bloomberg stated recently that Greece has a 98% chance of defaulting in the next five years (although, as we speak, the EC and the IMF are trying to agree on another bailout).

The move seems yet another international blow for an already beleaguered country, but the decision is pragmatic: Schwan explained that some Greek hospitals haven’t been paying their bills for three or four years. “There comes a point where the business is not sustainable anymore,” he added, not unreasonably. There has been talk across the EU of co-opting the private sector to underwrite a portion of the eurozone losses, but clearly Roche (and others) have already been doing this as far as Greek hospitals are concerned. Even the most philanthropic private sector company is going to have to think hard about dishing out ‘aid’ to a country in Greece’s position.

But as Jeff Harding writes on dailycapitalist.com, it is the eurozone that is in serious trouble; Greece is “just a symptom.” From a creditors’ perspective, following the logic of the ‘domino effect’ that threatens to envelop similarly cash-strapped countries (Italy, Spain, Portugal), Roche, and eventually the rest of Big Pharma, might find itself having to cut off supply to hospitals all over Europe. So far the Swiss drugmaker has countered the ethical implications of its draconian move, saying patients in Greece haven’t been deprived of their medication as a result. (They now have to take their prescriptions to a local pharmacy, and bring them back to the hospital if they need to be administered by a specialist.) Thus, it is considering implicating the same measures in Spain. But just how feasible is this for large and increasingly elderly patient populations? We may find there is more of an outcry when similar cut-offs are imposed on countries that are currently viewed with more sympathy than Greece.

This isn’t shock news exactly — the company’s announcement of an imminent cost-cutting initiative was widely reported in September and the mooted cost-savings and number of job losses has been much speculated on. But the final announcement of the figure — which swells to 5,500 when the jobs to be transferred to third-party outsources are factored in — makes for depressing reading when added to the roll call of announced and planned Big Pharma layoffs of the last two years. Since 2008 this has stood at — Pfizer: 16000; Schering-Plough: 6000; Merck: 7000; J&J: 7800; AstraZeneca: 7600. (A fuller list is available this month in Pharm Exec’s ‘Inside Outsourcing’ supplement.)

Still, analysts are pointing to a sliver lining for Roches. John Bird of Datamonitor maintains that the restructuring will help in the long run. Despite the slow down in performance over last year — mainly due to a decline in demand for Roche’s influenza drug Tamiflu — Bird says “the company’s operating profit in 2009 was above average and the cost savings announced will help cement Roche’s strong fiscal position over the next six years.

You have to abate to accumulate, it seems.

This is a huge problem for Roche who purchased the treatment as part of its merger with Genentech. The drug firm could see sales drop by $1 billion if FDA agrees with the panel and ceases use of the drug for breast cancer. The drug earned Roche $5.7 billion in 2009.

“We are disappointed by the committee’s recommendation and believe Avastin should continue to be an option for women with this incurable disease,” stated Sandra Horning, Roche’s global head of clinical development hematology/oncology, in a release. “We will continue to discuss the data from the more than 2,400 women who participated in three Phase III studies with the FDA. This recommendation does not impact Avastin’s approved uses for other cancer types.”

Avastin (in combination with chemotherapy) was given fast-track approval in early 2008, because it treated HER2 negative breast cancer, a form of the disease with few treatment options. FDA requested that Genetech release the results of two post-market trials to determine how effective the drug is at improving patient lifespan.

According to the two trials, the treatment only slowed cancer progression by approximately a month and didn’t do anything to boost patient survival. Additionally, patients taking Avastin had more adverse reactions than patients taking chemotherapy alone.

FDA will give a final ruling on Sept. 17.

I had the opportunity to catch up with a few seasoned participants who are widely known throughout the HBA for their commitment to the organization—Charlotte Sibley with Shire, Ilyssa Levins, president of the Center for Communication, and Shellie Caplan, founder of Caplan Associates. First timers like Ellen Chi, principal research scientist in San Diego for Johnson & Johnson, came out to get prospective on career development. “It’s not too common you find women in pharma, so it’s nice to hear how women in the industry [at the conference] started their careers,” she said.

Hot topics of conversation are in long supply, including plenty about two companies: Roche and Genentech. And it’s no surprise: At the peak of transition and in HQ territory, the merger is one change never quite experienced before in pharma, said Jennifer Cook, vice president portfolio management of Genentech, who opened today’s morning welcome address by sharing her thoughts. “The culture of leadership that emerges for this new company will be most important,” she said. “We’ll need every employee going through this time of transition to ask themselves ‘what can I do?’”

The keynote speaker, best selling author Libby Gill, might have provided the solution. Gill shared three strategies for creating a culture of bold leadership: Develop your own leadership DNA or determine how you lead; clarify, simplify, and execute your vision of success; and then pursue a radical sense of purpose.

But perhaps the highlight of Gill’s speech came when she shared an ancient proverb to a ballroom with more than 600 women in it: “If you’re leading and nobody is following, maybe you’re just taking a walk.”

Well, I doubt anybody’s “walking” here. Empowered women are everywhere and ready to change the status quo. Stay tuned to find out how Renee Tannenbaum, chief commercial officer, Elan Pharmaceuticals, is leading her company’s operations to new heights.

In addition to inflammation, the Nutley operation serves as headquarters for Roche’s oncology disease biology area, as well as RNA therapeutics—an emerging area based on increasing understanding of how genes are activated in cells. Pharm Exec recently got the opportunity to speak with the facility’s Director of Human Resources Marcie Geremakis, who shared her thoughts about the ongoing recruitment process.

Pharm Exec: What are the biggest challenges for HR during these times?
Marcie Geremakis: One of the challenges we’ve been addressing is that on the Roche Nutley site there are some functions moving to San Francisco as part of our acquisition of Genentech. It’s a growing mode, so we have to make it clear to the external world that we’re growing and looking for people to come in. We always want to represent ourselves truthfully to a candidate that this is happening.  

Another challenge when recruiting a candidate is to present the mission of research at Roche, making it very clear that this is what we’re all about, this is what the job is about, and this is what their responsibilities would be. In a time of organizational change, it’s very important to do that with a clear and consistent message to a candidate coming into any organization.

PE: How is Roche creating a work environment that encourages innovation, and vouching for job security in midst of such a challenged business model?

MG: By being committed to clarity as a message and purpose as an organization. We are committed to delivering and communicating news to employees. In the research world, we’ve made the mission of our research very clear, including our goals for 2010 and 2011.

I think that people find stability in our message. They also become aware of the type of work environment we have here at Roche, at Nutley in particular, and how we value talent and how we take care of talent. So, I think that’s the message [potential employees] get both when we interview them and when they come on board.

PE: What is being done at the company to address corporate reputation?
MG: It’s a very exiting time for the people we’re bringing to Roche for the first time. With the acquisition with Genentech, we are forming a new relationship, so the research population is very excited about Roche’s prospects for the future. The message has been a motivating factor.

I don’t want to leave out the other units at Nutley that have been affected by the transitions. However, in this time of organizational change, we as a company have handled it very well.

PE: How do you envision the human resources role at pharmaceutical companies in the near future?
MG: Roche is a company that embraces the HR function. In these times of organizational change, it’s a key part of the business, and one thing we’ve maintained is our focus on talent management. We work very hard at developing employees and giving people an opportunity to broaden their skills. At this time, we have to be even more diligent in helping our current employees to develop and remain productive in a stable environment. We also have to acquire the right type of talent as the initial step in [seeding] the talent pipeline.

That is where HR has served the business well at Roche research. HR is part of every leadership team on the Nutley site and globally. We have a strong presence in how the organization functions and will continue to lead new initiatives to move the business forward.

The risk of over-production has paid off: world orders for swine vaccines will see billions of dollars in extra revenue for the biggest pharma companies. GlaxoSmithKline, Roche, Sanofi-Aventis, Novartis, and Baxter are all expected to report very healthy first-half earnings as a result of a wealth of government contracts for vaccines and antiviral medicines.

According to a report in the UK Financial Times, GSK has sold 150m doses of its pandemic flu to the UK, US, France and Belgium, and sales of Roche’s Tamiflu have been boosted by orders from the both the public and private sectors. From the US government alone,
Novartis has received an order for $346 million for antigen and $343.8 million for adjuvant, a total sale of nearly $690 million. Total swine flu vaccine sales could ultimately net Novartis between $1 and $1.5 billion.

But, ahead of the publication of the company financial reports, there already seems to be indications of potential backlash about pharma’s return on investment with regard to the swine flu orders. In the UK media, GSK has already been obliged to justify the price of approx. £6 per dose that it has set for its vaccine, with CEO Andrew Witty explaining: “We’ve deliberately been very responsible about pricing — the vaccine is not being sold at a special premium…”

The pandemic has been saturating the UK news much more than in other countries; in the US, it has featured nowhere near as prominently on the agenda. The UK media is notorious for turning against those that it previously championed. One wonders, then, whether this price-based backlash is likely to spiral over the coming months, as the vaccines finally hit the market.

It’s very possible, in the UK at least, that the knights in shining pharma that promised to come to the swine flu rescue just a few weeks ago could be soon be subject to the wrong kind of press attention — once again!

“Clearly, people who are used to abusing domain naming system for drug names are doing it for the Swine flu as well,” said MarkMonitor chief medical officer Fred Felman. “They are using the brand Tamiflu to try and gain some credibility to sell products from pharmacies that are uncertified. It’s predicating sales on the fear and concerns of people.”

Typing Tamiflu in Google returns a number of sponsored links to online pharmacies, mostly claiming to be in Canada. None are official sites of the drug’s manufacturer, Roche. More than half make reference to swine flu.

MarkMonitor, authors of the annual “BrandJacking” report, track the existence, content, and brand use of a Web site. The company does not have access to transactional data, nor can it account for the credibility of the drugs being sold.

“Based on previous buying experiences—we have bought drugs in the past—the drugs are rarely real, and most often the product is never shipped,” Felman said.

Who’s Watching Who
So who should be responsible for taking down these sites—FDA or the pharma companies? At the moment, it seems the Web-hosting companies and search engines are taking the lead. Both Google and Yahoo are quick to take down problematic and/or illegal paid search ads, and hosting sites such as GoDaddy have been authorized to remove infringing sites without notification (if they fall on a banned list).

FDA, in the past week, has issued at least a half dozen warning letters to companies claiming to sell a cure or prevention medication for H1N1. However, if the Web site isn’t created on US soil, it doesn’t have to abide by FDA’s rules.

“The important thing for the pharma company is to have tools in place to identify abuse so that they can take action, because the brands that suffer worst are the ones that don’t do anything,” Felman said. “If you let this fester, and let the criminals think your brand is an easy target, that’s who they’ll target. If you enforce, you see counterfeiters move to another brand.”

Roche could not be reached for comment by deadline.

• Just days after its purchase of Genentech, Roche has made another acquisition, albeit a much smaller one, of the German firm Innovatis. Roche will pay EUR 15 million for the cell analytics company.

• Oxford Gene Technology (OGT) is to acquire Sense Proteomic, a UK-based company engaged in the discovery of disease-specific biomarkers based on its innovative functional protein array technology.

• ACM-Pivotal, which provides clinical trials services to the pharmaceutical and biotech industries, has been acquired by its US counterpart for an undisclosed sum. Following a management buy-out in 2005, Pivotal and ACM Medical Laboratories formed an alliance to extend their global capabilities and have been operating as ACM-Pivotal for the past three years.

• US-based contract research organization (CRO) Covance has expanded its clinical pharmacology footprint in Europe by acquiring Swiss Pharma Contract (SPC), a clinical research company based in Basel, for an undisclosed sum.