The standard cognitive test used for trials of drugs for Alzheimer’s disease is not accurate, UK researchers have found.

The ADAS Cog test, which scores patients on an aggregate of 11 components (such as language use and naming objects), underestimates the progress of dementia and variance between patients.

The report suggests that some Alzheimer’s drugs, including ones that ‘failed’ clinical trials, may be more effective than was thought.

In particular, the test is unreliable as a means of tracking the early stages of dementia, where drug interventions are likely to have most impact.

Researchers from Plymouth University examined 675 ADAS Cog test results for people with mild Alzheimer’s disease at zero, six, 12, 18 and 24 months.

Analysis of the scores at component level revealed a ‘ceiling effect’ in relation to eight abilities: from 32–83% ‘passed’ the component with equivalent scores.

A follow-up study used Rasch analysis, a technique for evaluating aggregated tests, to confirm the flaw and suggest improvements: parts of the ADAS Cog need to be more difficult, and the overall scoring method needs reworking.

“It is impossible to say precisely the extent to which the ADAS Cog’s flaws have undermined the numerous clinical trials in which it has been used,” said study leader Professor Jeremy Hobart.

“It has been used, unchanged, for many years and its apparent contribution to suboptimal trials has led a number of drug companies to rethink their strategies.

“However, it is very clear that in its current form the ADAS Cog underestimates cognitive differences between people and changes over time.”

The test “is not working in people with mild Alzheimer’s disease,” he concluded.

The ADAS Cog was recently used in the ‘unsuccessful’ drug trials of Lilly’s solanezumab and Pfizer and J&J’s bapineuzumab.

Both GlaxoSmithKline (GSK) and Eli Lilly are investing in new pharmaceutical research facilities in the UK.

GSK has provided £12m to help fund a new sustainable chemistry research facility, focusing on pharmaceutical research, at Nottingham University.

Lilly has launched new neuroscience research facilities at its Erl Wood R&D campus in Surrey, at a cost of £5.4m.

Both initiatives reflect the industry’s renewed confidence in partnership with the academic sector, triggered in part by the new ‘patent box’ legislation.

Known as the GlaxoSmithKline Carbon-Neutral Centre for Sustainable Chemistry, the new building at Nottingham University is intended to stimulate collaborations with other institutions and industry partners.

The new building, scheduled for completion in 2014, will be carbon-neutral, made from natural materials and rely on renewable energy sources.

Sir Andrew Witty, CEO of GSK, said: “The carbon-neutral laboratory will help affirm the UK as a global hub for the future of the life sciences industry. This is an opportunity to invest further in science in the UK, rethink how we approach the drug discovery process and play a role in contributing to environmental stewardship.”

“This development will be transformational in several ways,” commented Professor David Greenaway, Vice-Chancellor of the university. “The building will break new ground in sustainable construction, while the centre of excellence will shape the future of drug discovery.”

The initiative was praised by David Willetts, Minister for Universities and Science. “This new laboratory is an excellent example of collaboration between universities and industry,” he said. “It shows how businesses can benefit from the knowledge and expertise of our world-leading research base and will help keep us at the very forefront of life sciences.”

Eli Lilly’s new research facilities at Erl Wood will house 130 staff, many already employed at the site.

The investment reflects Lilly’s aim of strengthening its neuroscience portfolio, especially for the treatment of Alzheimer’s disease.

Dr Jan Lundberg, President of Lilly Research Laboratories, commented: “The UK is a great place to do bioscience research. Not only does the UK benefit from have a strong research base, the government is also able to maintain a stable pricing and reimbursement system.

“As well as financial incentives for R&D, this demonstrates that the UK government has a commitment to maintain its position as a global leader in attracting pharmaceutical investment.”

Lilly’s involvement in neuroscience research goes back two decades. The company’s drug solanezumab, currently in phase III development, has potential to slow the progression of Alzheimer’s disease.

Dr Lundberg also emphasised the importance of partnership between industry and academia. “Collaboration is absolutely essential to ensure innovative new medicines reach patients,” he said. “The science behind drug discovery is becoming more challenging.”

Novartis is expected to overtake Pfizer and become the biggest manufacturer of prescription medicines by 2018, according to new consensus data.

Research by EvaluatePharma estimates Novartis will record sales of more than $50bn in six years’ time, with its eye care business Alcon and generic unit Sandoz driving growth.

But the outlook is not good for US-based companies with only Pfizer remaining in the top five by 2018 and Sanofi, GSK and Roche maintaining a strong presence.

Data found that despite generic competition on Diovan and Glivec and disappointment from key projects such as Gilenya and its new respiratory franchise, Novartis is expected to record annual growth between 2011 and 2018 of 1.2%.

This is in contrast with AstraZeneca whose annual sales are expected to drop from $32.4bn in 2011 to $22.1bn in 2018 representing a negative growth of 5.3%.

Gilead Sciences is expected to experience the biggest increase in annual growth of the top fifteen companies with data showing sales will rise from $8.1bn to $15.7bn at a rate of 9.9% per year.

Novo Nordisk is also forecast to enter the top 15 ranked companies for the first time due to an increasing demand for its diabetes medicines. Annual growth is expected to be 7% until 2018 with sales totalling nearly $20bn.

One of the biggest casualties, data found, will be Eli Lilly. The Indianapolis research-based company currently claims to be the 10th biggest pharmaceutical company in the world. But Lilly fails to make the top 15 companies after research found a drop in sales will see it fall to 17th place by 2018. But researchers did note that Lilly’s Alzheimer’s candidate, solanezumab, could reverse the trend if it successfully enters the lucrative market.

Lilly will be replaced in the list by German healthcare giant Bayer, which also enters the top 15 global companies for the first time, with annual sales of around $16.5bn by 2018 boosted by Xarelto.

Eli Lilly Chief Executive John Lechleiter believes his company needs to focus on exploiting the potential of its pipeline instead of making drastic cost savings to overcome revenue loss.

Speaking at the annual meeting of the Pharmaceutical Research and Manufacturers of America in Boston, the CEO said that savings alone would not be enough to tackle the challenges of generic competition on its two main products.

“I don’t think we can save our way out of the enormous challenge we face,” he said. “The best course is to maintain our focus on advancing our pipeline.”

Lilly expects to lose up to $3bn this year after its psychotic disorder drug Zyprexa lost patent protection in a number of major markets. Gemzar was also exposed to generic competition for the first time last year. Exclusivity for its depression treatment Cymbalta is also set to end in 2013.

The company’s leading experimental product is solanezumab, used to treat Alzheimer’s disease. It is currently in Phase III trials. Analysts have predicted the drug could be a “lottery ticket” for Lilly if approved, and generate sales of up to $9 billion by 2020.

Mr Lechleiter insists the success of solanezumab will not define the future of the pharmaceutical company and revealed the company was developing other treatments for Alzheimer’s. “Lilly’s future does not depend on solanezumab,” he said. “While we hope the molecules that we take into Phase 3 will be successful, we’ve said all along this is a high-risk program.

“We have other approaches and other molecules in our pipeline that we will continue to move forward.”

Despite the CEO’s savings claim, Lilly decided to impose a global salary freeze for the majority of its employees to help it manage the ‘patent cliff’ in February 2012.

Pfizer’s experimental treatment for Alzheimer’s disease is the industry’s “best chance” of successfully fighting dementia, according to its research chief Mikael Dolsten.

Dolsten said that bapineuzumab, co-produced with Johnson & Johnson, had far stronger phase II clinical trial data than Eli Lilly’s rival solanezumab.

Pfizer’s new dementia drug is central to its current strategy of developing new products through partnership, thereby generating new ‘blockbuster’ drugs while cutting its R&D budget.

Speaking at the BIO conference in New York, Dolsten claimed bapineuzumab to be “so far the best chance the industry has for disease modification in Alzheimer’s”.

Alzheimer’s disease is estimated to affect 35 million people worldwide, and a drug that effectively delays the progress of dementia has become a ‘holy grail’ of the industry.

Pfizer and Lilly both plan to release the results of major phase III trials of their respective drugs in the second half of this year.

Lilly restricted its phase II trials of solanezumab to 12 weeks, whereas Pfizer devoted 18 months to phase II trials of bapineuzumab – leading Dolsten to comment: “Bapineuzumab was the only one of these two that had significant phase II data.”

The difference in approach means that Pfizer has been able to set up much larger phase III studies.

However, its phase II studies achieved mixed results. While patients in one phase II trial had almost 25% less accumulation of amyloid plaques (a suspected marker of Alzheimer’s disease) in the brain, they showed no cognitive benefits relative to those on placebo.

Both rival drugs treat patients who have already developed mild to moderate symptoms of dementia, making effective treatment very difficult. Dolsten noted that the best results would come from early diagnosis and treatment.

Pfizer is depending on its drug pipeline to overcome the negative effects of patent expiry on sales of Lipitor and other leading products. Its other new potential ‘blockbuster’ drugs include Prevnar 13, an improved form of its Prevnar vaccine against streptococcus bacterial infection; and tofacitinib, an experimental drug for rheumatoid arthritis.

Dolsten also predicted that Pfizer would develop an anti-smoking vaccine and major new treatments for diabetes and cardiovascular disease.

He noted that, having cut its annual research budget by $2 billion, the company was now looking to collaborate with other pharma companies for drug development.

Pharmaceutical giant Eli Lilly has announced a salary freeze for most of its global employees, including its senior management, to help the company survive its ‘patent cliff’.

After a quarter in which its ‘blockbuster’ antipsychotic Zyprexa lost 44% of its former market due to generic competition, the company is looking to a new dementia drug to lead its future portfolio.

In a recent US Securities and Exchange Commission filing, Lilly declared that in response to “the business challenges the company faces”, its employees in “most countries” would not receive base pay increases in 2012.

Lilly CEO John Lechleiter (pictured) and his executive team will also receive no salary increases in 2012. However, Lechleiter will receive the same $16.4 million bonus package as in 2011.

The pay freeze is intended to bridge the company from its loss of exclusivity on Zyprexa (olanzapine) to future successes. The failure of dementia drug semagacestat through negative trial results in 2010 has left the company without a fresh blockbuster.

The results of two key clinical trials of solanezumab, another Alzheimer’s medication for which Lilly has high hopes, are due by mid-2012.

Deutsche Bank analyst Barbara Ryan commented that these results may make the difference between a “significant” improvement in Lilly’s long-term “growth outlook” and the prospect of being “forced to reconsider its business strategies”.

Last week Lilly reported that sales of Zyprexa had fallen by 44% to $749.6 million in the last quarter of 2011, a much worse impact than it had forecast. As a result, the company’s Q4 profits fell by 27%.