GSK isn’t the first pharma company to set its eyes on the automobile industry. In 2009, AstraZeneca borrowed some experts in lean manufacturing from Jaguar Land Rover, who were to apply their knowledge of efficient car production techniques to medicines. I’m researching at the moment how the project went so watch this space and hopefully I’ll be able to provide an update on this in the near future.

So what is it that cars and pharmaceuticals have in common? Today, the majority of a car’s value is attributable to suppliers but before this the industry used to be dominated by Western companies, much like the pharma industry. As the industry found the need to implement aggressive streamlining and cost cutting, carmakers now maintain only a few core operations, with everything else taking place across a huge network of contractors.

In the pharma industry, we’re already seeing greater numbers of companies outsourcing certain functions, such as clinical trials, or in-licensing new compounds from smaller companies.

The article (available here) pulls out a lot more similarities between the two industries. If you like pharma and cars then it’s definitely worth a read!

The article doesn’t provide any updates on the GSK partnership, which is a shame because it’s something I’m really looking forward to hearing more about. Where as AstraZeneca was looking to cars for lean expertise, GSK is hoping to extrapolate some of the technology using in Formula 1 racing to improve its R&D, such as seeing whether real-time monitoring technologies can be applied to human studies.

Related articles

 Fast Pharma – The Best of British

Last week, the World Intellectual Property Organization (WIPO), an agency of the United Nations, founded WIPO Re:Search, a forum for public and private organizations to share intellectual property (IP) and expertise with global-health researchers. By establishing a public database of IP, WIPO Re:Search aims to help develop new drugs and vaccines to treat neglected tropical diseases, malaria, and tuberculosis. The National Institutes of Health and companies such as AstraZeneca, Eisai, GlaxoSmithKline, Novartis, Pfizer, and Sanofi have agreed to work with the group.

To join WIPO Re:Search, member organizations agree to let the group license their IP to researchers on a royalty-free basis in many cases. But some observers say that these terms will not make information accessible enough. “Instead of allowing all countries where neglected diseases are prevalent to access the products, the initiative restricts royalty-free licenses to least-developed countries only, with access for other developing countries negotiable,” said Doctors without Borders in a press statement. Many patients that suffer from neglected tropical diseases do not live in least-developed countries. “In the Americas, for example, Chagas disease affects 21 countries, but the consortium will only provide royalty-free licenses for Haiti, where Chagas is not endemic,” according to the statement.

I think that WIPO’s initiative has great potential to help ease suffering and save lives. It’s encouraging to see the pharmaceutical industry dedicate resources to treating diseases that do not necessarily represent lucrative markets. And, by pooling a large amount of expertise, collaborations such as this one promise to solve stubborn problems more quickly than might otherwise be the case. But Doctors without Borders seems to be raising legitimate concerns. Considering its overall profitability, does the pharmaceutical industry have an obligation to help countries in need?

The answer to that question as it was discussed reflected many of the larger and well-chronicled trends affecting the pharmaceutical industry, such as generic-drug incursion, declining R&D productivity, and the ongoing need for cost reduction in development and manufacturing. At one level, these pressures make outsourcing an attractive alternative to internal development and manufacturing as a means to reduce fixed cost structures and achieve greater flexibility, which is a plus for CROs and CMOs. On the downside, however, CROs and CMOs face greater competition as pharmaceutical companies, particularly large pharmaceutical companies, seek to reduce their supplier base and partner with strategic, if not preferred, providers as the choices for these potential CROs and CMOs broaden globally.

So how do CROs and CMOs make the cut or stay in the game and achieve a competitive advantage? Some suggestions offered by pharmaceutical companies were integrated service offerings, higher levels of project management, specialized technical offerings, and other approaches that meet the evolving needs of pharmaceutical companies in realizing their goals for greater flexibility while maintaining reliability and quality of supply. The choices for CROs and CMOs relate to how to adapt their business models either through increased service offerings, partnering with other contract service organizations to achieve a fuller slate of capabilities, and finding opportunity in the globalization of the pharmaceutical contract service industry. Not an easy task, but one in which has become a basic requirement for participation in the market for pharmaceutical chemical outsourcing.

Just last week, Representative Michele Bachmann (R-MN) told Fox News that the vaccine for human papillomavirus “can have very dangerous side effects.” Bachmann, who hopes to be the Republican candidate for president next year, mentioned a mother who claimed that her daughter had suffered mental retardation because of the vaccine.

Bachmann has taken a lot of heat for her remarks. The American Academy of Pediatrics and public-health efforts have denounced them. Arthur Caplan, a bioethicist at the University of Pennsylvania, offered to donate $10,000 to the charity of Bachmann’s choice if she “can produce a case in one week . . . verified by three medical experts that she and I pick of a woman who became ‘retarded’ (her words) due to the vaccine.”

Unfortunately, Bachmann is not the first to question vaccines’ safety. For years, a small but vocal group has been claiming that the vaccine for measles, mumps, and rubella causes autism. Early this year, the research paper that lent credence to this claim was revealed to rely on sloppy science and questionable methods. More recently, a panel assembled by the Institute of Medicine found no evidence that the vaccine causes autism.

Rumors that vaccines are harmful continue to circulate even in the absence of sound evidence. Comments such as Bachmann’s help foster this misperception. The group warning about vaccines’ putative dangers may be small, but it has gained media attention and could potentially influence patients’ decisions about healthcare. The pharmaceutical industry, and public officials such as FDA, would do well to publicly reaffirm that vaccines are safe. Drugmakers could describe the safety information garnered during clinical trials of their now-approved vaccines. And perhaps FDA could include a Q&A about vaccines on its website to dispel doubts. Communicating accurate information about vaccines will help the industry and patients alike.

This week, it wasn’t a vegetable that commanded the media’s attention (although this morning I did come across a piece touting the benefits of spicy broccoli for fighting cancer); instead, the flower, the British Autumn crocus, stole the spotlight following the release of a press statement from the UK’s University of Bradford. According to the statement, researchers have created a drug that has the potential to find and destroy solid tumours, regardless of cancer type.

The drug’s key active agent is based on colchicine, a natural compound that was derived from the crocus. Most media headlines have sensationalised the research (examples include: Tumors effectively cured with crocus drug,  Crocus drug that can kill tumours in one treatment with minimal side effects and Flower-powered ‘smart bomb’ to beat cancer, scientists say), but when you look beyond the hype, there’s some intriguing science.

Colchicine is well-known for its anti-cancer properties, but is highly toxic against normal tissues in the body. The researchers, however, have designed a delivery system that prevents colchicine from being active around the rest of the body where it could damage normal cells. The release of colchicine is triggered by an enzyme from a family of proteases called Matrix Metalloproteinases (MMPs), which is only usually present in high amounts in tumours.

“One role of this particular MMP in cancers is to dig a path for the tumour to grow bigger and develop new blood vessels that will help nourish the tumour,” Professor Laurence Patterson, Director of Bradford’s Institute for Cancer Therapeutics (ICT), explained in a statement. “Our novel delivery method uses the presence of this active MMP to activate the drug which attacks and breaks down cancer blood vessels, destroying the tumour’s lifeline.”

Five different types of cancer have been tested in the laboratory using mice — breast, colon, lung, sarcoma and prostate. According to the researchers, in one study, half the mice showed complete tumour remission after a single dose. The team is now in discussion with a funder to take the drug through the final stages of preclinical assessment, after which clinical trials are planned to start at St James’s University Hospital in Leeds.

Back to reality

The research (and the accompanying media sensationalism) has caused a massive stir, but the UK’s Cancer Research was charity was quick to point out in a detailed blog that the research is a long way from curing human cancers. There’s also no guarantee that it will ever be possible to translate the findings into humans (see my related blog post A Rat is Not a Human!).

Cancer Research also points out something else; the press release seems to be based on peer-reviewed work that the researchers published in July 2010. “As far as we’re aware, the team haven’t published any new results since their 2010 paper,” said Cancer Research.

It’s not all disappointing news, however. The research is still a step forward in the fight against cancer and Cancer Research admits that the research is intriguing, although it does remain cautious in its outlook.

“The researchers’ results so far are impressive, but they’re just one of several hundreds of similar intricate approaches taken to tackle cancer by researchers around the globe, which are generally referred to as ‘enzyme-prodrug therapy’, and involve activating a harmless form of a drug near or in a tumour… Overall it’s fair to say that this kind of approach is still at a relatively early stage, although the Bradford results are certainly impressive, and their beauty is in their relative simplicity.”

Related blogs and news from PharmTech
Sensationalizm Strikes Again

Research Spend On Cancer Doubles Within A Decade

A Rat is Not a Human

Earlier this month, FDA approved Roch’s Zelboraf (vemurafenib) and companion diagnostic for BRAF mutation-positive metastatic melanoma. Zelboraf is an oral, small-molecule kinase inhibitor indicated for treating patients with unresectable or metastatic melanoma with the BRAF V600E mutation as detected by the cobas 4800 BRAF V600 Mutation Test, a polymerase chain reaction-based diagnostic test developed by Roche. The B-Raf protein is a key component of the Ras-Raf pathway involved in normal cell growth and survival. Mutations that keep the B-Raf protein in an active state may cause excessive signaling in the pathway, leading to uncontrolled cell growth and survival. These mutations of the B-Raf protein are thought to occur in an estimated half of all melanomas and 8% of solid tumors. Zelboraf is being codeveloped under a 2006 license and collaboration agreement between Roche and Plexxikon, a member of the Daiichi Sankyo Group. “The FDA approval of Zelboraf marks a major step forward in personalizing the treatment of metastatic melanoma, a devastating disease that until this year had limited approved treatment options,” said Hal Barron, M.D., chief medical officer and head of global product development at Roche, in a company press release.

Among the pharmaceutical majors, Roche is most active in pursuing a strategy of combining molecular diagnostics with targeted drug development. Such an approach has the potential of developing more clinically efficacious drugs, albeit to a smaller, but better defined patient population, which serves the pharmaceutical side of the business, but also Roche’ molecular diagnostics business. 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. The recently approved Zelboraf and related diagnostic test was one of those six treatments.

Analysts are bullish on Zelboraf as a potential blockbuster due to the drug’s potential in addressing an unmet medical need in treating metastatic melanoma. It will be important to watch the financial results for this newly approved drug and related diagnostic as well as the pipeline progression of Roche’s other personalized medicines to see whether the marriage of targeted therapeutics with related molecular diagnostics may indeed represent a new winning paradigm in drug development.

Some key drug approvals thus far in 2011 include AstraZeneca’s Brilinta (ticagrelor), a cardiovascular drug, which is being positioned as a potential blockbuster to complete against the platelet inhibitor Plavix (clopidogrel) by Bristol-Myers Squibb and Sanofi, according to an Aug.1, 2011, press release by Burrill & Company, a life-sciences financial-services firm. Plavix was the second highest selling drug in 2010 on a global basis, trailing only Pfizer’s Lipitor (atorvastatin), which was the top-selling drug. In 2010, Plavix posted global sales of $8.8 billion, according to IMS Health.

Other key approvals thus far in 2011 were: Incivek (telaprevir), a hepatitis C drug by Vertex Pharmaceuticals; Yervoy (ipilimumab), a melanoma drug by Bristol-Myers Squibb; and Benlysta (belimumab), a lupus drug by Human Genome Sciences, noted the Burrill & Company analysis. More than a dozen other drug candidates are scheduled for FDA review by the end of the year, according to the Burrill analysis.

As noted by Burrill & Company, seven months of data in terms of approvals does not in of itself make a change  in terms of improved R&D drug productivity, but at least it is a positive sign. During the past five years (2006–2010), FDA has approved on average 22 new drugs per year (21 in 2010, 26 in 2009, 24 in 2008, 18 in 2007, and 22 in 2006), according to FDA information. The recent 10-year high was in 2004, when FDA approved 36 new drugs.

It is not likely that in 2011 or in the near term, the industry will reach the level of productivity achieved in 2004, but at least thus far in 2011, there is good news on the drug-approval front.

Some drugmakers have blamed what they see as a slow and overly cautious FDA for the industry’s weak pipelines. Last week, I cited drug-approval figures to show that the agency was not standing in the way of innovation. A closer look at the figures contradicts another part of the critics’ argument—the industry’s pipelines may not be so weak after all.

So far this year, FDA has approved 20 new molecular entities (NMEs), according to The Wall Street Journal. That’s nearly the same number of NMEs that the agency approved throughout all of 2010. “We’re seeing a lot of innovation, much more than in recent memory,” Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research, told The Wall Street Journal. She went as far as to say that the industry had reached a “turning point” in drug development.

The change in the industry’s approach to research seems to be helping to enhance its development productivity. Many companies have shifted from an expensive, and potentially wasteful, “mass production” approach to one that relies on collaboration. Bristol-Myers Squibb’s (BMS) recently approved melanoma drug was originally discovered by a scientist at the University of California, Berkeley. The scientist worked with small biotech company Medarex to develop the drug, which eventually appeared on BMS’s radar. After BMS and Medarex formed a partnership, the rest was history. Shire also has used this collaborative strategy successfully.

Woodcock’s comments reaffirm my belief in the industry’s ability to market innovative drugs that improve patients’ lives. If the pace of NME approvals continues at its current level, it will soften the blow of the patent cliff for many companies. Maybe reports of Big Pharma’s impending death are greatly exaggerated.

Only 40 of the more than 270 publicly traded large-molecule companies are profitable, and the rest must rely on venture capital. Companies without products on the market are having a tougher time attracting funding these days. Up-front payments have decreased about 55% in the past five years, according to Ernst & Young. Money is increasingly contingent on achieving drug-development goals. This strategy might help investors get returns more easily, but it could discourage the kind of risk-taking research that produces real innovation. Indeed, it’s becoming less important for companies to have scientific expertise and more important for them to have “market awareness,” Glen Giovannetti of Ernst & Young’s global biotech unit told Bloomberg.

Investors’ reluctance to fund early-stage biologics firms has hurt the latter’s research and development (R&D) budgets. Companies without products on the market had to decrease research spending by 1% in 2010, according to Ernst & Young. Small biopharmaceutical companies are thus cutting their research budgets just as many traditional pharmaceutical firms are doing. It seems to me that this continuing trend could become a vicious cycle in which small biologics companies keep spending less on research, which in turn prevents them from discovering potentially marketable products that could keep them afloat.

Biopharmaceutical companies do seem to be more innovative than traditional pharmaceutical companies. But it looks like the large-molecule playing field could shrink over time as big companies get bigger and small companies fail. This shift would mirror the evolution of the small-molecule industry. Likewise, market pressures are already making it harder for early-stage large-molecule firms to get R&D funding—and encouraging a conservative approach to research. If the biopharmaceutical innovation engine eventually runs out of gas, what will the drug industry do?

Definitely, says the Hay Group, a management-consulting firm. Big Pharma’s executive-compensation plans reward compliance and short-term financial gains when they should be encouraging risk-taking, according to the firm’s research. About 80% of criteria that determine incentives are financial, and only 12% relate to drug development and commercialization. Although short-term incentives are common, they’re inappropriate for the pharmaceutical industry because of its long product-development processes, according to Hay Group.

In light of Hay Group’s research, the compensation package for former Pfizer CEO Jeffrey Kindler makes no sense at all. The company was facing distinct problems when its board gave Kindler the boot in December 2010. Not only had Pfizer’s share prices languished for four years, several promising drugs had failed in late testing, including a potential replacement for Lipitor. Despite these problems, Kindler got a 60% raise over his 2009 compensation. A performance-related bonus brought his compensation to $4.9 million. Kindler seems to have been rewarded for failure, which, to my mind, is even worse than being rewarded for short-term gains.

To overcome its current challenges, Big Pharma will have to change how it defines, measures, and rewards performance, according to Hay Group’s research. Fortunately, Big Pharma can use mid-sized drugmakers and biopharmaceutical firms as models. These companies “have been much more creative in weaving pipeline and R&D measurements into their incentive strategies,” said Hay Group in a press release. By learning from these firms’ compensation strategies, Big Pharma might match their level of innovation.

It’s easy to blame circumstances for our failings, and harder to admit our own missteps. If it took Hay Group’s recommendations seriously, Big Pharma might reclaim its reputation for innovation. And achieving this goal naturally would be good for the world’s patients as well as for industry.