This week Eli Lilly’s Eric Siemers offered a detailed look at the experiences of Alzheimer’s patients followed after the failure of its high-profile, late-stage study for semagacestat at the Alzheimer’s Association International Conference in Paris. The study was halted about a year ago after researchers determined that patients taking the drug scored worse on cognitive skills compared to the placebo arm. They also demonstrated an increased rate of skin cancer.

In the follow-up, Siemers said that the semagacestat patients continued to fare badly on cognitive skills, failing to recover and return to baseline after they stopped taking the treatment, a gamma secretase inhibitor. And as the Wall Street Journal notes, that could have serious consequences for researchers at Bristol-Myers Squibb and EnVivo Pharmaceuticals, who have been studying similar types of Alzheimer’s drugs.

BMS says it is closely looking to see if its drug triggers a similar effect in clinical trials. A spokesperson for EnVivo contacted FierceBiotech today to note that its Alzheimer’s program is a modulator of gamma secretase rather than a direct inhibitor, which it believes will steer clear of the same safety concerns raised by semagacestat. And other experts say that the jury is still out on that class of drug.

“I don’t think it’s dead,” Marc Cantillon, executive director of the Coalition Against Major Diseases, tells the WSJ. But anyone operating in the same development field would have to study the Lilly data closely.

Challenged with  series of setbacks on its late-stage pipeline,  Eli Lilly is setting to take a new approach for its early research and development programs. The US pharma hopes to share some of the R&D costs through the new approach.

Lilly plans to raise up to $750 million through three funds; and the company will put $50 million as a starter for each fund.  Extra  funding will be from venture capitalists. A slate of experimental drugs will be explored by virtual drug companies, with Lilly getting first shot at licensing any promising therapies developed as a result of the program.

 ”We think this is a very different kind of model,” Lechleiter, the Lilly CEO, told the Times. “This way we are not limited by our own resources and we can have more ‘shots on goal.”

This new approach will expand the company’s early-stage pipeline without forcing Lilly to foot the entire R&D bill. Additionally, the developer can select the most promising programs to advance into mid and late-stage trials. 

Eli Lilly is teaming up with the Juvenile Diabetes Research Foundation (JDRF), a leading charitable funder of type 1 diabetes research,  to support study of  regenerative medicine for treatment of type 1 diabetes.

The organisations will fund an early-stage research work looking for new approach of reprogramming selected cells to convert them into insulin producers, which would replace the ones destroyed by the disease.

The funding will be targeted at the research project led by Dr Pedro Herrera at the University of Geneva.  The research will be focused on investigating how alpha cells in the pancreas can sometimes spontaneously turn into insulin-producing beta cells. This project will last for three years and will receive financial support worth $1.4 million  from Lilly and JDRF.

 “We are delighted to be partnering with Lilly in this study. The regeneration of beta cells is a very exciting area of research for JDRF and whilst this research is at an early stage, we are hopeful that it could lead to better treatments for type 1 in the future,”  said Rachel Connor, Head of Research Communication at JDRF..

Dr Philip Larsen, chief scientific officer for diabetes drug discovery at Lilly, said: “This research is an example of regenerative medicine, a new frontier in science that replaces or regenerates new cells, tissues or organs.”

Lilly recently established a diabetes focused research centre in China  and started to collaborate with Boehringer Ingelheim on the development of a number of new diabetes drugs created by both companies.

An FDA experts panel said Thursday that  the  Alzheimer’s imaging agent Amyvid (florbetapir) from Eli Lilly is not ready  for approval in a vote of 13-3.  However, all the panelist agrees that the imaging drug designed to help screen for Alzheimer’s disease could be useful if the company can set up an effective training program to show physicians how to use it–and prove that the training works. The panel of advisers voted 16-0 in favor of approval for Eli Lilly’s Amyvid on the condition that the company demonstrates the images can be consistently interpreted by physicians who have received training in reading the scans.

Amyvid is an injection agent under development for highlighting brain plaque in medical imaging scans. While panelists said the chemical helped improve visibility of the plaque, they were concerned about the widely different interpretations when doctors examined the brain scans.

Lilly is applying for the approval of Amyvid to spotlight beta-amyloid in the brain, a condition that occurs in Alzheimer’s. But the company said it is not trying to use it to diagnose the disease, as there’s still no consensus on whether large concentrations of the protein actually trigger the illness.

Eli Lilly aquired the experimental drug Amyvid when the company bought its developer, Avid Radiopharmaceuticals last year with $300 million.

Alzheimer’s affects 5 million seniors in the U.S. and will take an even greater toll as baby boomers move into old age. The disease attacks neurons in the brain, leading to problems with memory, thinking and behavior. There is no cure for the disease, and scientists aren’t even sure what causes it.

Eli Lilly announced a global agreement with Boehringer Ingelheim to jointly develop and commercialize four experimental diabetes compounds that are in mid- and late-stage development, as well as an option to include a fifth compound.  The compounds in the porfolio are Boehringer Ingelheim’s two oral diabetes agents, linagliptin and BI10773, and Lilly’s two basal insulin analogues, LY2605541 and LY2963016. The deal also covers the option to co-develop and co-commercialize Lilly’s anti-TGF-beta monoclonal antibody.

Under the terms of the agreement, Lilly will make an initial EUR 300 million one-time payment to Boehringer Ingelheim. Boehringer Ingelheim will also be eligible to receive up to a total of EUR 625 million in success-based regulatory milestones for linagliptin and BI10773.  Lilly will be eligible to receive up to a total of $650 million in success-based regulatory milestones on its two basal analogue insulins, and a further $525 million should Boehringer Ingelheim elect to take its options on the anti-TGF-beta antibody. The companies said they will share ongoing development costs equally.

“We are very excited about this new and extensive alliance with Boehringer Ingelheim, with whom we have partnered successfully in the past,” said John C. Lechleiter, Ph.D., Lilly chairman and chief executive officer. “Working together, we will comprise one of the most robust diabetes pipelines in the pharmaceutical industry. For Lilly, this alliance expands our range of offerings for people with diabetes, strengthens our diabetes care capabilities and offers the prospect of near-term revenue opportunities as we address the upcoming loss of patent exclusivity for several of our products.”

Eli Lilly announced that the US regulators had approved their new underarm testosterone lotion, which the company acquired last March from Acrux, an  Australian drug delivery business.  The approval leads to an $87 million milestone payment for Acrux, which saw its shares jump to a record AU$3.36.

“Lilly is proud to expand our focus in men’s health,” said David Ricks, president, Lilly USA. “The addition of Axiron to our product portfolio reinforces Lilly’s commitment to provide innovative treatment options for patients.”

The testosterone replacement therapy have approved in several forms including tablets, skin patches, injections and topical gels. The company hopes that the Axiron underarm spray delivery will be preferable to other forms of dosing.

It is estimated that as many as 13 million men aged 45 or older in the United States have symptoms of low testosterone, including decreased sexual desire, fatigue, depressed mood and osteoporosis.

Adverse reactions reported during clinical testing of Axiron included skin reactions, increased red blood cell count, headache, diarrhea, vomiting and an increase in blood levels of Prostate Specific Antigen, a screening marker for prostate cancer.

Lilly gets the rights of the Alzheimer’s diagnostic Florbetapir

Eli Lilly & Co said on Monday that it would buy privately held Avid Radiopharmaceuticals, a Philadelphia based company for up to $800 million.  Under the terms of the agreement, Lilly will pay Avid $300 million upfront  to acquire the diagnostics company that is developing a diagnostic agent for a protein linked to the degenerative brain disease Alzheimer’s.

Avid could also be eligible to receive up to another $500 million milestones depending on future regulatory and commercial achievement relating to florbetapir, a Phase III-stage imaging agent used with positron emission computed tomography (PET) for identifying Alzheimer disease (AD) plaques in the brain.

“The acquisition of Avid Radiopharmaceuticals aligns well with Lilly’s innovation-based strategy, offers potential near-term revenue opportunity, leverages our neuroscience expertise, and will immediately bolster our diagnostics capabilities,” commented John Lechleiter, Lilly chairman and CEO. “We look forward to partnering with Avid’s experts during the regulatory process for florbetapir and are intent on gaining FDA approval for this promising diagnostic intended to help clinicians and researchers identify the presence of beta-amyloid plaque in the brain..”

Avid’s florbetapir was designed to test for fragments of beta-amyloid plaque in the brain,  which is a main suspected cause of Alzheimer’s disease. The agent, now awaiting US regulatory approval, is the first beta-amyloid imaging compound to enter multi-centre clinical studies in the U.S.

The compound has  been evaluated in more than 12 trials and 700 healthy and AD patients to date, and additional clinical studies in the EU, South America, Australia, and Asia are also under way.

Data from an analysis of the first six subjects enrolled in the Image-to-Autopsy study showed that the florbetapir PET images correlated strongly with postmortem histopathology findings. The PET images correctly identified which subjects had beta-amyloid deposits but also showed where in the brain the deposits had accumulated.

In addition to florbetapir, Avid is also carrying out Phase I/II trials with 18F-AV-133 for imaging vescular monoamine transporter (VMAT2) in disorders such as Parkinson disease and dementia with Lewy bodies, which involve dopaminergic degeneration. Avid is separately undertaking early clinical evaluation of its 18F-VMAT2 PET compounds for imaging beta cells in the pancreas as a potential approach to diagnosing beta-cell dysfunction associated with type 1 and type 2 diabetes.

Lilly has suffered setback in the Alzheimer’s pipeline as the company halted the development of semagacestat, a new agent as a potential treatment for Alzheimer’s disease as two late-stage studies showed it didn’t slow the disease’s progression and may have even worsened patients’ conditions.

Cymbalta usage extended

Eli Lilly’s blockbuster antidepressant Cymbalta (duloxetine hydrochloride) has received expanded approval from the U.S. Food and Drug Administration to treat chronic musculoskeletal pain, stemming from conditions including lower back pain and osteoarthritis.

Since its approval as an antidepressant in 2004, some 30 million people in the United States have used the drug. Chronic musculoskeletal pain is the fifth indication the agency has granted for the drug.  The US regulator also has sanctioned Cymbalta for the treatment of diabetic pain, generalized anxiety disorder and fibromyalgia.

It is already used ‘off-label’ for a range of conditions such as musculoskeletal problems, headaches and nerve pain, noted the FDA, which assessed the efficacy of Cymbalta in chronic low back pain and osteoarthritis in four trials involving 600 patients. At the end of the study period, patients taking Cymbalta had a significantly greater pain reduction compared with placebo.

The most common side effects from Cymbalta use include nausea, dry mouth, insomnia, drowsiness, constipation, fatigue, and dizziness. More serious adverse reactions have included liver damage, allergic reaction, pneumonia, depressed mood, and suicidal thoughts and behavior, the agency said.

The FDA has also warned that Cymbalta should never be used in patients who have recently taken a type of antidepressant called an MAOI, or Mellaril (thioridazine), or who have uncontrolled glaucoma.

The approval comes after the FDA’s Anesthetic and Life Support Drugs Advisory Committee voted 8-5 in favour of expanding the pain indication but 4-9 against supporting its use to treat osteoarthritis, concerned about the known serious side effects associated with the drug. These include liver damage, allergic reactions, pneumonia, depressed mood, suicide and suicidal thoughts.

New Diabetes Centre Deepening Lilly Presence in China

Eli Lilly said today the company is planning to open a new research centre focused on diabetes in China, “where the incidence of the disease has reached epidemic proportions”.  Estimated 92 million people in China – 10% of the adult population – are sufferers of diabetes, according to a recent publication in New England Journal of Medicine. 

 The new R&D centre will be based in Shanghai, where Lilly’s main operations and R&D efforts are located, the new centre, headed by Bei Betty Zhang, vice president of research for Lilly Research Laboratories in China, will initially employ 100 scientists and support staff, “the majority of whom will be hired from within China”, the company stated.

 David Moller, head of endocrine and cardiovascular research and clinical investigation at Lilly, said that “given key differences in the molecular basis of diabetes in Chinese and other Asian populations, a major focus at this centre will be on discovering therapies that target critical aspects of the disease.”

 ”Our strategy in China, and throughout the world, is to bring innovation to patients,” said Jacques Tapiero, senior vice president and president of Lilly’s emerging markets business area. “By establishing a diabetes research center in China, Lilly will be better able to discover medicines that are well suited to the particular needs of patients with diabetes in China.”

 The company is working with the China Diabetes Society and the European Foundation for the Study of Diabetes to support collaborative programmes between Chinese and European academic centres. It has committed 1.8 million euros over three years to the scheme.

 Jan Lundberg, president of Lilly Research Laboratories, added that the Shanghai facility “will complement our existing network of collaborations in China and also will enable us to further gain the insights of China’s talented scientists inside and outside of Lilly”.

 Lilly’s presense in China can be traced back to the early 1990s. The company has R&D operations based in Shanghai and manufacturing facilities in Suzhou. Lilly Asian Ventures,  a venture capital fund focused on the Chinese bio-pharma industry, was established in 2007 and has made more than $40 million investments so far.

 The company has a mojor diabetes product portfolio including  the Humalog and Humulin product families for type 1 disease, and Byetta and Actos, for type 2 diabetes, and Lilly’s R&D pipeline includes experimental thearapies for diabetes and other metabolic disorders in various stages of clinical development.

 Lilly’s pipeline suffered a few setbacks recently. Last month Lilly and partner MarcoGenics have to stop enrollment into ongoing clinical studies with the humanized anti-CD3 monoclonal antibody teplizumab, due to disappointing Phase III results.

Also in last month, the company and its partners Amlyn, Alkermes confirmed that the US FDA had requested additional trial data on the type 2 diabetes drug Bydureon, before it could consider approving the therapy.