Personalized medicine has been one of healthcare’s most anticipated and least understood treatment paradigms. Physicians remain optimistic regarding its future, however the 52 doctors surveyed differed in their views in its implications for therapeutic research and development (R&D). Patients, by contrast, were viewed as increasingly interested in embracing the therapy.

Physicians were asked in which therapeutic areas do they feel the use of personalized medicine—for example, the use of genetic testing to tailor drug therapy to an individual—would be most prevalent. Of the doctors surveyed, nearly 58 percent said oncology/hematology, followed closely by cardiology (48 percent), allergy and immunology (38.5 percent), endocrinology (32 percent), and rheumatology (nearly 29 percent). In contrast, doctors felt the therapy would be least common in orthopedic surgery and obstetrics/gynecology.

Clinicians disagreed, however, on whether financial incentives are strong enough to encourage widespread collaboration between developers, payers, consumers, and pharma. When asked, “How will the adoption of personalized medicine affect the priorities and processes for pharma/biotech R&D?” physicians’ anonymous responses ranged from, “More opportunity for profit will drive new genetic testing,” to “No effect.” (It should be noted that a greater percentage of doctors did feel that opportunities for profit and for developing new drugs would increase.)

The Cost of Adoption
Much like a new consumer technology or ‘green’ product, the limits to widespread adoption are directly affected by the costs to the patient or payer. This is backed up by the Lehrman/Bloomberg survey, in which nearly 81 percent of respondents felt the adoption rate was directly affected by the willingness of the patient or payer to pay. And even when personalized medicine is adopted, 79 percent of physicians feel it would be only narrowly embraced.

These numbers are based on several factors, not least of which is the collaboration between diagnostics companies, drug makers (including pharma companies and biotech firms), patients, and physicians, the combination of which is where survey respondents think the big push will come from. Several clinicians believed that therapeutic companies would continue to target known genetic situations where biomarkers are linked to disease. Others believed that the entire R&D paradigm would change to link effective therapy to individual patient genetic profiles. The biggest detriment to adoption seemed to fall on whether the right incentives are in place to foster collaboration between the therapeutic and diagnostic companies toward developing personalized medicine therapies—are the financial incentives strong enough to encourage the collaboration needed?

Overall, what is garnered from the Lehrman/Bloomberg survey on The Future of Personalized Medicine is that diagnostic and therapeutic companies will have to partner to champion wider adoption rates. It is this participation that will help to alleviate payer and patient concerns over paying for additional screenings as well as higher targeted therapy costs.

ACCESS TO MEDICINE INDEX 2010

GlaxoSmithKline ranked number one in a study of pharmaceutical companies offering access to medicines to emerging and developing nations, proving that the UK drug giant has a far stronger grasp on new markets than its US and Japanese counterparts.

The study ranks 20 companies based on significant criteria including pricing, patents and intellectual properties, capacity enhancement, marketing, lobbying tactics, competition, and philanthropy.The study was the brainchild of Wim Leereveld, founder and chairman of the NGO, Access to Medicine Foundation, in partnership with research firm Risk Metrics.

This is the second index that the foundation has published. The first, released in 2008, featured data submitted from only nine companies. This year, 19 of the 20 pharma firms were open and transparent with their information.

High Marks All Around
So what separates GSK from the competition?

“GSK has integrated access to medicine into its core business model, so it’s not philanthropy, it’s really part of the way they do business and part of their understanding of the importance of emerging markets,” said Afshin Mehrpouya of Risk Metrics. “As a result, they are heavily engaged in research for neglected diseases. At the same time [they are] able to sell their drugs in the emerging markets, they help with the development of the infrastructure.”

Companies at the middle or the bottom of the list treat access to medicine as a tactical issue rather than including access to medicines as a major part of their business, Mehrpoua explained.

The biggest mover among Big Pharma companies was Pfizer, which ranked 17 in 2008, but moved up to number nine this year.

“Pfizer is now seen as a player,” Leereveld said. “The company has changed dramatically. All the people [in that division] are gone and there is a new team that see [access to medicine] as a very relevant matter to perform in developing countries and they did their utmost to get their data together.”

European companies, in general, have has a longer history operating in emerging markets, giving them a lead on Japanese and American firms that relied for many years on local markets for sales.

“Given the saturation of the Western market, the decline of the blockbuster drugs, and the fast growth of the emerging markets, companies like Pfizer are moving faster to catch up with their European counterparts,” Mehrpouya said.

The Japanese are taking a play from the US pharmaceutical industry’s rulebook and restructuring itself under the auspices of a fun catch phrase: “Transformation for a New Takeda.”

The punch line, however, isn’t too funny.

According to a two-year mid-range plan announced yesterday, Takeda will cut about 1,400 positions in the US to fend off loss of revenue due to looming generic competition. That number includes about 28 percent of the sales and marketing division and 20 percent of employees at the drug development center, according to Business Week.

Takeda’s billion-dollar blockbuster Actos is set to lose patent exclusivity in two years, and the company is still reeling from generic competition with its heartburn medication Prevacid.

Most of the job losses will be in the Chicago offices, particularly in the Deerfield and Lake Forrest offices and R&D center. According to the company, it plans to “shift to lean and flexible marketing organizational networks that can flexibly respond to changes in the business environment and product mix.”

“Takeda has experienced halted development in some pipelines and delays in obtaining drug approvals,” it stated in a release. “The company has therefore decided to respond flexibly to these changes in the business environment and ensure a sustained growth trajectory by developing and implementing a Mid-Range Plan starting in the fiscal 2010, one year ahead of schedule.”

Takeda is forecasting a net profit loss of 26 percent and a 4.5 percent drop in sales. The company is banking on a number of new products—primarily in metabolic/CV, oncology, and CNS. It currently has four new treatments filed, and another 10 in Phase II trials. The company expects to recover by 2016.

Biotech firm InterMune took an ugly hit on Tuesday as news broke that its lung disease drug Esbriet (pirfenidone) will require additional clinical studies, and won’t be getting the seal of approval from FDA any time soon. The news caused InterMune’s stock to drop a staggering 78 percent, according to Reuters. Analysts have downgraded the stock to values as high as $60 and as low as the mid-teens.

Esbriet is being used in trials to treat patients suffering from idiopathic pulmonary fibrosis (IPF), a debilitating and deadly lung infection that causes inflammation and scarring. People suffering from the disease typically have only two to five years to live and a 20 percent survival rate.

The treatment was involved in two large-scale clinical trials, but the drug failed to meet its endpoints in one. However, the Phase III data that the company collected was expected to be enough to get the green light from FDA.

In a complete response letter to InterMune, FDA requested another clinical trial to further prove the efficacy of Esbriet, beyond the endpoint met in the previous study. There are currently no FDA-approved medications for IPF, and an FDA advisory committee recommended that the treatment be approved back in early March.

Dan Welch, chairman, CEO and president of InterMune, said that he intends to meet with FDA as soon as possible to find out why its committee rejected the drug, and understand how to expedite the approval process. The bad news is that the meeting may not occur for 60 to 90 days.

Welch would not elaborate on the kind of data FDA would like to see, or what type of trial the regulatory body is looking for, nor would he comment on previous discussions with FDA.

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Here’s why:

More competition. Nearly two thirds of the R&D pipelines of the major innovative drug companies are now focused on specialty drugs. Assuming some of these will be authorized for sale, the result is going to be increased competition and declining market exclusivity per therapeutic category – mirroring the trend already evident in primary care.  The overall impact is more choice for payers, leading to increased pressure on specialty’s ability to command premium pricing.

Fiscal pressures. More of the high cost burden for specialty drugs is being passed on to patients. This is shredding the argument that specialty drugs are “special needs” and thus exempt from the normal dictates of a price-conscious consumer market. The ability of industry to determine how patients contribute to the cost is critical to specialty, due to a smaller prescribing base, the need to keep as many patients as possible on therapy, and the importance of tracking compliance with complex regimens,.

Unfortunately, the trend in pharmacy benefit programs is to replicate “one size fits all” solutions introduced for asymptomatic and chronic care medicines. Industry thus has to focus on creative ways to help a key untapped constituency – the under-insured – pay for high-end specialty drugs. Occupying the vast middle ground between subsidized low-income patients and the larger self-insured employer and union pools, the needs of the under-insured must be addressed. Failure to do so will make the specialty pricing model politically non-viable. Its fate will be no different than the path for so-called “me too” drugs – can CMS negotiated prices or even price controls be far behind?

Value. Specialty’s future depends on living up to its name – the business imperative is differentiate or die. In other words, define your value to the customer, or the customer will do it for – to – you.  The challenge here is that industry is not really stepping up to the plate with the hard evidence of value where it counts, in improving health outcomes, against existing products and from a system-wide perspective. A recent survey of US payers conducted by Amerisource Bergen found that 50 per cent felt they had “zero” input into the development process for new specialty drugs, with a mere eight per cent finding it “adequate.” And almost all this input occurred during the Phase III stage, which is equivalent to stopping the clock at the eighth inning, with bases loaded.  Will companies really want the input at that point, or more directly can they do anything about it?

The discussions set up a stark display of two alternative futures. One is the politicians’ vision of a commoditized drug world focused on basic primary care. Innovation will drive more toward finding efficiencies in low cost services to meet budget priorities, rather than spreading the adoption of new technologies widely enough so smaller diseases or indications get priority. The other is the flexible application of innovation in drug discovery to seed the promise of personalized medicine, where specialty drugs can justify higher price points if they can demonstrate real value as a coordinating driver toward better health outcomes.

Achieving this latter outcome – which carries significant advantages to both industry and the patient – depends on investing a lot more in customer-based insight and doing what that insight actually tells you. Is big pharma alert and nimble enough to adapt to a environment where good prices are simply the result of a value proposition agreed with the customer? The answer will determine whether specialty remains special.  If past is prologue, what do you think?

“The difference is that I think smaller companies take more risks in Phase I and II,” said Anthony DiTonno, CEO of NeurogesX. “They make mistakes like big ones, but in our case, we were lucky enough to have a package of Phase III trials approved in Europe, where authorities view neuropathic pain differently than the US does. One of the interesting things is the difference between the regulatory pathways.”

Since neuropathic pain is very different than acute traumatic pain, it’s not something primary physicians see often. Thus, the sales team will target a very specialized group of physicians who treat nerve signal disorders. “Our approach is to capture roughly the 15,000 to 25,000 physicians out there who spend their day treating this, which includes calling on physicians in pain centers and hospitals,” said DiTonno.

Initially, the company plans to put 30 to 35 people in the field, and ramp that number up based on sales. The plan basically overlays physicians’ prescriptions by zip code. For example, in zip code 00000 there are X amount of prescriptions generated for Product A by a specific type of physician. DiTonno notes that by doing it this way, “you get to more intelligently deploy your sales force.”

So what happens if NeurogesX doesn’t receive get approved? According to DiTonno, that depends on the audience. He cautions, however, that one thing is most important for small pharma to remember: Put yourself in a position to be successful by doing all the planning you can while being extremely conservative with resources.

“Be really strict as you can be in deploying your human and financial resources. In early 2007, we decided that any activity not directly related to approval didn’t begin. We didn’t start any new clinical developments.”

In light of the economic meltdown, and the tough times that all of pharma has experienced, DiTonno emphasized that cash is king, and a kingmaker must manage it efficiently. “It’s a balance between planning for success while making sure that in the event there is a delay or a hiccup, you have the cash available to get you through whatever that hiccup may be.”

The deal adds more than $3 billion in annualized sales to its global pharmaceutical business—three-quarters of which are in international markets. Abbott will be adding the ex-US Solvay pharmaceuticals to its existing pharma division, which has been growing in double digits on an operational basis, according Abbott CEO Miles White.

“We are adding from a position of strength,” White said in a conference call. “Our business has performed well in developed countries with branded products, such as Humira.”

Solvay offers Abbott a portfolio of complimentary products in cardiology, neuroscience, and gastroenterology; as well as new compounds, such as pancreatic enzymes and hormonal therapies.

Abbott also gains control of Solvay’s vaccine pipeline—an area Abbott has yet to enter—and a small diagnostics business. Seventy percent of Solvay’s business is branded generics, sold mostly outside of the United States.

Solvay is currently trying to boost its $200 million influenza vaccine business by establishing cell-culture production capabilities to be used for seasonal and pandemic flu vaccines.

The biggest gain for Abbott is Solvay’s existing penetration in emerging markets. Solvay is currently active in 50 countries with products in 150 countries. Solvay has a broad emerging markets infrastructure with a presence and brand loyalty in Russia, Brazil, and India.

White estimates combined sales in emerging markets to be about $4 billion by 2013. Solvay sales in Russia last year exceeded $150 million; twice what Abbott sold in that country.

“Solvay also gives us approximately $500 million in additional incremental research and development capacity that we’ll use to drive future pharmaceutical growth,” White said. “This extra funding power also provides us with additional flexibility to access opportunities through licensing and external partner agreements.”

Abbott expects the transaction to close in the first quarter of 2010.

Steven Paul, Lilly

Last week, Lilly announced a major restructuring plan focused around the creation of one Developmental Center of Excellence and several individual business units. The media (Pharm Exec included) focused on the news that 5,500 jobs were being cut as part of the plan. This week, we’re talking to Lilly to find out what the company’s R&D structure will look like beyond the elimination of positions.

Steven Paul, president of Lilly Research Laboratories and executive vice president of science and technology, filled Pharm Exec in on the details.

Could you clarify the role of the new Developmental Center of Excellence? Is it simply a coordination vehicle?

Its main purpose is to speed innovation to patients and to the market. Yes, it is a coordinating vehicle—we have put there the key functions for clinical development, including all the key elements such as process research development, regulatory, safety, and project management. There is going to be a single operating model at Lilly, which we piloted for the past 12 to 18 months, and that’s something we call critical chain, which is a way of seamlessly developing drugs.

Why the change?

The reason we are doing this is because we have a terrific Phase I and II pipeline—we have 64 individual molecules in development, 21 in oncology, and our goal is to get those molecules into Phase III and into the marketplace and to patients.

There are three key pillars from a technology and methodology perspective. One is critical chain methodology—a project management tool that we piloted. One hundred percent of the projects using critical chain methodology are on track, either at or ahead of their milestones, as compared to about 60 percent of our traditional development projects. We will expand this to all of our projects by the end of this year.

The other pillar is something we call advanced analytics. This is the use of clinical trial modeling and simulation, as well as adaptive, seamless design. In other words, moving from Phase I to II and from Phase II to III without stopping.

We piloted this on four projects. We literally determined the dose in Phase II—in a multi-arm study—moved the two doses that were optimal into Phase III without stopping, and continued on with the commercial development of the molecule.

This can save enormous amount of time, and you can do it on the front end. For a few molecules you could probably do it for Phase I, II, and III. Not all molecules will meet the criteria for this. It obviously requires that you have enough clinical trial material. But when you have a validated target and the molecule is behaving very well in Phase I through proof-of-concept, at that point, these kinds of trials can literally cut years off the development time of a molecule.

The third pillar of this Center of Excellence is the idea of tailored therapies. Lilly has been very successful with tailoring, but we now believe that it needs to be applied across the portfolio in a much more robust way, beginning in Phase I and not after a drug is in Phase III or on the market. Tailoring the right patient, right dose—these are essential for determining whether a drug works.

Are you altering the end points in a trial as a molecule is moving through the trial?

Not necessarily the end points. For example, because the purpose of Phase II is to pick the dose of a molecule—and to confirm efficacy and safety—you usually stop at the end of it. You look at the data, look at the best two or three doses, and move into Phase III. This way you can stop the doses that you don’t want and enroll patients into the programs that you do want.

You can also do this on the basis of tumor response. Let’s say you are in Phase II for an oncology drug that works in breast cancer. Now we know that virtually no oncology drug works for all people that have breast cancer. But let’s say you have a marker—logical or molecular—now you can determine which type of breast cancer is responding to your drug and without stopping. You literally keep enrolling patients that have that type of breast cancer.

CNS doesn’t seem to have its own business units, yet it has been a major Lilly franchise.

I think this was misinterpreted in the press release and something we are trying to clarify with the public. We are very interested in CNS, and the biggest products we have right now are CNS drugs—Zyprexa, Cymbalta, etc. But they are mature products that will lose patent protection over the next few years, beginning in 2011, so they were put into the developed markets business unit. But we have a very robust science pipeline. In fact, we have two Phase III molecules for Alzheimer’s disease. So we have not, by any means, lost interest or enthusiasm for CNS.

How are your business units different from similar models in other companies, such as J&J and Pfizer?

When we make a commercial decision on a molecule—traditionally after Phase II—at that point the molecule will move into the business unit with two exceptions. In oncology we will move all Phase I molecules into the business unit, because we often do Phase I trials for cancer in cancer patients. The other business units will pick up the molecules at the commercial decision time.

What about benchmarks? Is it all about speed to market or the number of new compounds being commercialized?

We have an unprecedented amount of molecules in early stages and mid stages, so our success as company as we transverse the patent cliffs is going to require that we speed innovation to patients. If you didn’t have enough good stuff to speed to patients, none of this will be effective. We feel we’ve got the quality molecules we need to make this work.

Is there a deadline for the restructuring plan?

This is all going to occur by January 1, 2010. We are well on our way for the Development Center of Excellence because we’ve been piloting critical chain, adaptive designs, and tailored therapies for some time. We are ready to go, and this will be rolled out at our analyst meeting in December.

Have you substantiated the number of people being laid off as opposed to positions being eliminated?

No. Frankly, we don’t have the answer to that question. We’ve done very well over the years with attrition. We’ve already reduced by 7,000 people by attrition over the last few years. We hope this predominately occurs by attrition, but obviously it might not. We don’t know the percentages, but that will all be worked out in the next few months.

Pfizer announced, last week, that it was partnering with technology firm Private Access to launch an online social network to help patients find clinical trials more easily.

According to Pfizer, a top complaint from physicians is difficulty in matching patients with trials. “Finding volunteers has been a big issue for anyone conducting a clinical trial. Not just pharma companies, but any researcher conducting a trial,” said Kristen E. Neese, director, worldwide communications, Pfizer.

The problem is twofold. One the one hand, patients are concerned about sharing their personal health information; on the other hand, there hasn’t been a central location for patients to look for clinical trials and have their information matched with the most appropriate trial for them.

Pfizer Senior Strategy Director Usama Malik told Pharm Exec on Wednesday that the difficulty finding patients is causing drugs to take longer to get to trials, and in turn, raising costs.

“The clinical trials industry is highly fragmented,” Malik said. “Pharma companies, traditionally, haven’t worked in unison to increase value. They don’t speak to each other about the holistic opportunity for patients, providers, and pharma [to work together].

The new site will offer best-of-kind services including:
• Education and awareness for specific conditions and clinical trials
• Trial recruitment via patient posts and traditional research requests
• Some form of social community

Since 2002, Pfizer has posted every clinical trial its been involved with on NIH’s trial bulleting, but the drug giant wanted to establish a network that offers a more personal experience for the user. “This builds on that by creating more of a social networking site where patients can share their information and find trials that meet their specific needs,” said Neese.

For example, a diabetes sufferer can go to clinicaltrials.gov, type “diabetes,” and get thousands of protocol listings. Sorting through the different criteria is daunting, said Neese. The new site will allow patients to determine if they want to share their private information with researchers who are looking for patients that meet their specific criteria.

Much as a person would be asked to befriend someone on Facebook, a patient could be alerted that a researcher is looking for patients with diabetes; the patient will then be asked if they would like to share their information with this researcher.

“We have a long term vision for this site that includes not only Pfizer clinical trials, but all clinical trials,” Neese says. “We want this to be a tool that is going to be useful to patients. For it to work, it has to include more than just Pfizer.”

The site is scheduled to launch within the next year.