The Big Red Biotech Blog

Was Clint Talking to John about Alzheimer's?

The other shoe that analysts have been talking about for a while now dropped today when Eli Lilly revealed that its Alzheimer drug, solanezumab, missed both its primary endpoints in a Phase III trial. Lilly's Lechleiter had at one time been touting this as an example of the internal R&D pipeline drugs that Lilly is expecting to lead it out of the wilderness.

He had backed off solanezumab as having to be the "saviour" though in the past few months when it became apparent that the drug would be a long shot to achieve it's clinical targets.  This was largely apparent as Pfizer's similar drug bapineuzumab failed earlier this year.

Lechleiter is not giving up yet though as he said their analysis shows the drug may be showing a positive trend in slowing cognitive decline in patients with mild-to-moderate disease. We'll see about that John.

See Fierce Biotech, Pharmalot, and In the Pipeline.

Posted by Bruce Lehr Aug 24th 2012.

Can Pharma Win the Alzheimer's Lottery?

According to the Wall Street Journal's interview of several wise guys in the institutional investment community? NO.

Wall Street Doubt Pfizer & Lilly Alzheimer’s Meds // Pharmalot.

"These drugs are long shot lottery tickets."  "Not playing. A fool's game. I have no confidence that we are anywhere near the technology to address the disease." "It's too critical not to be there -- risk/reward for the pharma group is still skewed to the upside."

Needless to say, we can be thankful most analysts aren't drug developers. They're not likely to be successful with that skepticism quotient.

In the meantime, Lilly and Pfizer keep plugging away in Phase III studies with solanezumab abd bapineuzumab respectively.  Both are expecting key results late this year.  At that time, we'll see if either has won their bet (as well as the patients targeted for therapy). If not?

The analysts say Lilly stock will drop to $37.40 (12%) and Pfizer will go down to $21.30 (6%).  And Lilly's Elan would plummet 30% to $9.80.  Just some more cheery news for your weekend.

Posted by Bruce Lehr Jun 22nd 2012.

Elan now Sitting Duck for Big Pharma Takeover?

PharmaGossip via an article from the Independent raises the question as to whether Elan is now a very attractive takeover candidate for Big Pharma now that it has sold its drug delivery business to Alkermes.

PharmaGossip: Elan move makes it a sitting duck for big boys -- Independent.ie.

Elan now is a "pure" neuroscience play with potentially attractive programs at at multiple sclerosis, Alzheimer's and Parkinson's disease. It has also lowered its debt from about $770 M to only $270 M and has cash balances hovering around $500 M. 

This should make it look a lot prettier to suitors and likely accounts for its stock increasing by 8% last week. Rumors suggest that J&J could be first in line as it already owns 50.1% of Elan's Alzheimer's unit to foot the rest of the bill to acquire it. Posted by Bruce Lehr May 16th 2011.  

Next Alzheimer's Hope Step Forward

There is some buzz in the news today about an eagerly awaited Alzheimer's drug, bapineuzumab, as it progresses in a pivotal phase III trial. The drug is being developed by Elan/J&J and Pfizer. The popular press is touting the drug as a potential - 1st drug - to treat Alzheimer's rather than just ameliorate symptoms for relatively short periods.  It may be the first drug approved that can delay or prevent disease progression.  It does this by binding the amyloid beta protein.  We'll see as the trial results become available as to its effectiveness.

I can understand the anxiousness involved with possibly having an actual treatment for Alzheimer's but I think people need to keep perspective until the trial results are available to assess that it actually works -- or on which sub-populations it actually works. Alzheimer's is a tough area.  Just this past summer, Lilly's semagacestat went down and out in a pivotal phase III trial.  This drug too was aimed at preventing amyloid beta plaques --  though it is a gamma secretase inhibitor and worked by blocking an amyloid forming enzyme. 

Bapineuzumab is a mAb that works by binding a soluble form of the amyloid beta protein in the blood.  Thus, has a different mechanism of action from semagacestat.  Lilly does have another direct rival drug to bapineuzumab, called solanezumab, that is also in pivotal phase III trials.  Solanezumab puportedly will work with a wider patient sub-population and has a somewhat better safety profile though that too needs to be proven by the trial data. See Fierce Biotech and The Daily Mail.

Both newer drugs are touted as mega-blockbusters with peak revenue predictions ranging to the $3 billion plus annually.  However, both need to make it through their respective trials and to market through the appropriate regulatory agencies.  Until then, let's keep our enthusiasm tempered. See Investor Village link to Datamonitor report.

 
Posted by Bruce Lehr April 25th 2011.

Biogen Idec MS Drug Passes Clinical Test

Biogen reported that its oral MS drug, BG-12 (dimethyl fumarate), performed well in its latest pivotal trial and met its goal in reducing MS flare-ups over two years.  The drug also met secondary goals of reducing the number of new or enlargin brain lesions and slowing the rate of disability. 

BG-12 is on the cusp of joining Biogen's other MS stable-mates, Avonex (interferon B) and Tysabri (natalizumab), to stregthen its industry leading MS franchise. In addition to the benefits cited above, BG-12 was also said to offer a good safety profile and the convenience of taking it orally is considered big plus to patients. Biogen shares were up 5% on the news. See Xconomy.

 

 

Posted by Bruce Lehr April 11th 2011.

 

Medivation, Pfizer Fail in Huntington's Trial

Medivationa and Pfizer announced today that their drug, dimebon, failed to meet its end points in a pivotal trial for Huntington's disease.  As a result, development on the drug has been stopped.

Medivation, Pfizer Fail Huntington's Test.

A phase III trial utilizing the drug against Alzheimer's in patients with mild-to-moderate symptoms will continue.

Posted by Bruce Lehr April 11th 2011.

NIH hasn't Forgotten Neuroscience Drugs

Yesterday, I made a post concerning big pharma cutting back its investment in many areas of neuroscience due to the higher risk presented in this therapeutic area and the high costs associated with it.  It was also pointed out that much of the difficulty lies with there not being many good biomarkers and model systems to work in.

Today I see a post In the Pipeline that describes a development funding opportunity being presented by NIH in the neuroscience arena:

The NIH Blueprint for Neuroscience Research is establishing a ‘virtual pharma’ network of contract service providers and consultants and is soliciting applications for U01 cooperative agreement awards from investigators with small molecule compounds that could be developed into clinical candidates within this network. This program intends to develop drugs from medicinal chemistry optimization through Phase I clinical testing and facilitate industry partnerships for their subsequent development. By initiating development of up to 20 new small-molecule compounds over two years (seven projects were launched in 2011), we anticipate that approximately four compounds will enter Phase 1 clinical trials within this program.

There you have it.  The NIH is trying to assemble the resources (in a virtual network) and provide the funding encouragment to develop new therapies for neuro diseases. And, they appear to be serious in seeking results:

Applicants must have available small-molecule compounds with strong evidence of disease-related activity and the potential for optimization through iterative medicinal chemistry. Applicants must also be able to conduct bioactivity and efficacy testing to assess compounds synthesized in the development process and provide all pre-clinical validation for the desired disease indication. . .This initiative is not intended to support development of new bioactivity assays, thus the applicant must have in hand well-characterized assays and models.

The goal is to develop at least one novel and effective drug for a nervous system disorder that is currently poorly treated and to catalyze industry interest in novel disease targets. Not everyone is loathe to pick up the challenge of developing new neuro drugs.

 

 

 

Posted by Bruce Lehr March 29th 2011.

Brain Drug R&D Drain

Both the WSJ and Fierce Biotech wrote pieces on the seemingly worrisome trend for European pharma (GSK, AZ, and Sanofi) companies, and even US (Merck), cutting back their efforts in neuroscience. The companies indicated that the risk of failure was highest in the neuro area, it took longer to complete projects and it cost considerably more. 

Generally, this was conceded to be a problem of not having any real good biomarkers to speed the research. Suggested measures to improve the situation include:

• More government investment into basic neuroscience research in academic arena
• Shared development risk through government or public funding
• More private-public partnerships to develop drugs
• More big pharma, biotech and academic collaborations

The industry has also called on the regulators to help out by "fast-tracking" reviews in this area, and have asked that longer patent terms be granted.  Bascially, they are asking that someone help underwrite the risk.  This may be ok as long as commeasurate reward flows back to the underwriters as well.

Regardless, as things stand now, new medicines in schizophrenia, stroke, bipolar disorder, depression, anxiety and autism are likely to be slow in coming with the cutbacks.  Industry observers noted that over 20 years ago, a similar exodus occurred in pursuit of new antibiotics (albeit cause underlying reason was different) with the consequence that we are facing a dearth of new meds now to battle new resistant strains. This is viewed as a strategic mistake in the treatment corridors. It woudl be great if we didn't repeat with neuro diseases that currently rank number one in terms of cost to the health care system in Europe.

Posted by Bruce Lehr March 28th 2011.

Lechleiter Dead On with Amyvid Prediction - DOH!

Lilly's John Lechleiter, somewhat under duress due to a series of late stage failures in Lilly's pipeline, has been publicly bullish on the chances of Amyvid receiving FDA approval as a diagnostic for Alzheimer's disease.  Oops!

The FDA expert committee begs to differ -- at least for now.  Lilly was told by the committee to establish a training program to ensure reader accuracy and consistency of interpretation with the test. Lilly apparently has been aware of the training needs and is working on it. However, while this doesn't represent a another pipeline failure per se -- it does represent a delayed approval and a delay in much-needed revenue generation from this product.

Lilly has an agreement to pay up to $800 M to Avid as the diagnostic test meets certain milestones -- including a $300 M upfront.  It's tough to earn any of that $300 M back if you aren't on the market.  See Fierce Biotech. 

DOH!

 

 

 

Posted by Bruce Lehr March 18th 2011.

GSK/Impax Parkinson's Drug Hits Endpoints in Ph III

GSK and its parnet Impax Pharmaceuticals reported positive results with its drug IPX066 in a phase III trial with Parkinson's disease patients.  The extended-release version of the drug induced a 37% drop in off-time (when a medication's affect has worn off) compared to a 17% decrease in patients taking an immediate release version of the drug.

Article GSK/Impax drug impresses in Ph III Parkinson's trial.

Under the terms of the companies' development and commercialization agreement, Impax wil complete the current phase III program for IPX066 and will file the drug in the US later in 2011. GSK has an exclusive license to commercialize the drug worldwide, except in the US and Taiwan. Impax shares jumped more than 10% on the clinical results news.

 

 

Posted by Bruce Lehr March 16th 2011.

GSK and Actelion Do Not Have the Perfect Sleeper

Again as reported in Fierce Biotech, GSK and Actelion have pulled the development plug on their insomnia drug, almorexant over patient tolerance conerns. This after GSK had signed a deal with Actelion in 2008 for up to $3.25 B in upfronts and milestones.

Almorexant was targeted to treat insomnia and also Alzheimer's and insomnia-related depression (it is likely inducing some of this now!).  The drug had been projected by [very] eager analysts to hit peak sales of as much as $6 B annually - that's quite a Mother's little helper.

But now due to safety concerns, instead of putting people to sleep the drug itself will be laid to rest.

Goodnight Gracie.

 
Posted by Bruce Lehr Jan 28th 2011.

Lilly Alzheimer's Diagnostic Expected to Get FDA Approval

Seeking Alpha says it is only a matter of time before Eli Lilly's newly-acquired Alzheimer’s disease diagnostic, florbetapir, wins FDA approval.  Lilly purchased florbetapir last November for $300 M from Avid Radiopharmaceuticals. 

Florbetapir, also known as AV-45 and which Eli Lilly has branded Amyvid, is an imaging agent which binds to the characteristic beta-amyloid plaques found in the brains of Alzheimer’s patients. This essentially dyes the plaques, which can then be seen on a PET scan.  Amyvid will help doctors rule out the degenerative brain disease if there is an absence of plaques.

Amyvid, and other Alzheimer’s and dementia diagnostics, will really come into their own when therapies become available and early diagnosis becomes more important, although it is possible that simpler tools will be available by then. In the meantime, with a lot of research into therapies that target beta-amyloid, Amyvid could well find an important role in clinical trials. Eli Lilly has one of the most advanced agents pursuing this avenue, solanezumab, which breaks up the beta-amyloid clumps. Amyvid should be able to track this happening.

This will be interesting to watch. The industry seems to strongly believe that companion diagnostic tests will become very important  in the future with these more complex diseases in establishing treatment effectiveness or even identifying which patient classes should receive a given therapy.

 

 

Posted by Bruce Lehr Jan 23rd 2011.

Merck Serono Teams with Domain Therapeutics on Parkinson's Drugs

Merck Serono agreed to a $178 M deal with Domain Therapeutics to target new therapies for Parkinson's disease and other neurodegenerative disorders. The deal provides Domain with Eur 2 M upfront for R&D and potential milestones of another Eu 132 M.  Merck will gain access to Domain's G-Protein Coupled Receptor (GPCR) compounds.  See Fierce Biotech.

 

 

Posted by Bruce Lehr Jan 21st 2011.

Sanford-Burnham Strikes Deal With J&J for Alzheimer's Drugs

J&J signed a new drug development agreement with Sanford-Burnham Insitute to develop new drugs for Alzheimer's and psychiatric disorders.  The deal could be worth as much as $85 M to Sanford-Burnham. The deal is with the Ortho-McNeil-Janssen division within J&J.

Sanford-Burnham Strikes Deal With J&J, Second Big Pharma Alliance in a Month.

This is just the latest Big Pharma - Academic Insitute deal with several being announced in just the past few months - many between members of Big Pharma and UCSF.  Sanford-Burnham also has a similar deal to the J&J pact with Takeda Pharmaceuticals.

 

 

 

Posted by Bruce Lehr Jan 21st 2011.

 

Biogen Idec Buys Drug Rights from Neurimmune for $32.5M

Biogen Idec bought thre CNS programsfrom Neurimmune for $32.5 M upfront plus future payments up to $395 M in future milestones.  In acquiring the 3 candidate drugs targeted to the neurotoxic proteins alpha-synuclein, tau, and TDP-43, Biogen acquires potential therapeutics aimed at Alzheimer's, ALS (Lou Gehrig's disease) and Parkinson's.

Biogen Idec Buys Drug Rights from Neurimmune for $32.5M.

"Biogen Idec is committed to becoming the global leader in the development of innovative therapies for neurodegenerative diseases," said Alfred Sandrock, senior vice president, neurology research and development, Biogen. See Fierce Biotech.

 

 

Posted by Bruce Lehr December 21st 2010.

GE Aims to Bring Alzheimer Biomarkers to Life

Fierce Biotech reports that GE will team up with J&J to find new-presymptomatic biomarkers for Alzheimer's disease. The markers will be used to accelerate diagnosis and treatment. The two will try to use GE's Flutemetamol imaging agent to identify Alzheimer's very very early in disease progression.  The tool may help J&J and its partner Pfizer select patients for treatment with new Alzheimer drug candidates, like their bapineuzumab. 

"The collaboration we are announcing today is part of this effort to understand Alzheimer's," Pascale Witz, president and chief executive of medical diagnostics at GE Healthcare. "We think defining this biosignature could allow a major step forward in managing Alzheimer's disease in patients,"

 

 

 

Posted by Bruce Lehr December 3rd 2010.

Where Has All The [Drug] Innovation Gone?

The Pharmalot blog reports on new drugs introduced at the ACS Meeting in Boston -- and unfortunately on the lack of innovation exhibited by these drugs. Fifty-eight drugs were introduced and not ONE was directed toward a previously unidentified target. Yikes!

Where Has All The Innovation Gone? // Pharmalot.

This is consistent with a post I made a couple of days ago based on information from the In the Pipeline blog. This analyzed 252 drugs and determined 58% were from pharma (vs. biotech or univiersities) but only 36% of pharma's drugs were classified as innovative (vs 65% and 62% for biotech and universities respectively). 

Citeline's Ian Lloyd commented, "There is much talk in the industry about the move towards focusing on new and innovative therapies, especially in orphan conditions, but the hard evidence is failing to match the rhetoric.”

 

Posted by Bruce Lehr November 10th 2010.

All that's Lilly that's Fit to Print

There were a couple of pieces of news on Eli Lilly that came out yesterday.  Firstly, Lilly announced that it has struck a deal to buy Avid Radiopharmaceuticals for up to $800 M - structured as a $300 M upfront plus milestones up to $500 M.  See Fierce Biotech.

Avid is a diagnostics company that has developed a new approach for the detection of Alzheimer's with its molecular imaging agent, Florbetapir F-18, used to detect amyloid plaques.  F-18 has been submitted to the FDA for approval.  F-18 allows plaques to be detected in living patients brains - something currently unavailable until after the patient's death - so a proven diagnostic for the living is considered a big step forward. Plaques viewed by Florbetapir may be visible for up to 10 years prior to symptoms developing and the test might be used to monitor disease progression as well.

Lilly just had its lead Alzheimer's therapeutic drug Semagacestat go down in phase III clinicals earlier in the year - so this purchase of a companion diagnostic signals strongly that it hasn't given up on the Alzheimer's area for investment and drug development. Lilly is still looking for the Alzheimer's home run. It has solanezumab, an antibody designed to disrupt amyloid clumps, as its replacement lead candidate to Semagacestat.  Phase III results are expected next year.

Lilly also has a BACE called LY2811376 in phase I.  BACE acts to inhibit B-secretase thought to be involved in B-amyloid formation. Thus, the diagnostic test acquired might serve as a useful companion to both these drugs either in diagnosing patients earlier for treatment or in monitoring disease progression or drug efficacy. See Seeking Alpha.

Fierce Biotech also reported that despite the possible excitment that an Avid Radiopharmaceuticals acquisition might engender, the rating agency Moody's Investors downgraded Lilly to A2 - halfway between Aaa and junk. Ouch! Basically, Moody's says Lilly has lost global competitive position through patent expirations, pipeline setbacks, and disappointing product launches of drugs that actually hit the market. The triple whammy. And, Lechleiter still refuses to buy anyone large enough to impress the analysts given the factors cited above.

 Lilly may need to pull a rabbit out of a hat or at least its pipeline for this perception to change.

 

 

 

 

Posted by Bruce Lehr November 9th 2010.

 

Roche Breaks from the Herd

We seem to be able to count on Roche to pursue plans to differentiate itself from the herd.  Unlike many of its competitors who have stated an intention to pursue generics as diversification strategy (see previous post), Roche will remain true to its roots providing innovative medicines.  It plans to expand its historic franchise in oncology drugs to include new medicines in inflammation, CNS disease, and metabolic disorders.

Roche firmly rejects the idea of "diversifying" into generic drugs, consumer health or animal health.  Says CEO Severin Schwann, "A lot of people call it diversification. I call it giving up. Call me biased, but I really believe we have one of the best industry pipelines."  That's the spirit of leadership!

Roche still spends 21% of its revenues on R&D, and 57%of their current revenues come from oncology drugs.  The new shift to the three therapeutic areas mentioned above will require Roche to form some partnerships when it comes time to go to market - basically sales force deals to access physicians beyond its base of oncology specialists.

Says Schwann, "We go where science takes us."  He also talks about Roche retaining its faith in innovation - which already separates it from many of its following rivals. (See FT.com).

 

 

Posted by Bruce Lehr October 28th 2010.

 

Pfizer Said to Muscle Up in Pipeline

 According to an article in Fierce Biotech, Pfizer's new research chief, Mikael Dolsten proclaimed at the Morgan Stanley Global Healthcare Conference in New York that its pipeline is bulking up with new home grown products just busting to get out.

These include new drugs for arthritis, Alzheimer's disease and stroke prevention.  Dolsten said the company is also turning more to biotech (as the Wyeth acquisition no doubt indicates) for external partnerships and these will also extend to research institutions.

See the Reuters story for more.

Posted by Bruce Lehr September 14th 2010.

 

Approval Rates Higher for Small Firms in Top 50 - Tufts CSDD Report

In a new study, Tufts Center for the Study of Drug Development reports that approval rates for smaller pharma companies among the TOP 50 were higher than those for the TOP 10.   This is perhaps counter intuitive.

PR IR Sept-Oct 2010 | Tufts Center for the Study of Drug Development.

The study was based on 1734 compounds that entered clinical testing between 1993-2004. The following points came out of the study:

• Success rates were 30% higher for 30 smallest firms compared to the top 10
• Small molecules accounted for 85% of drugs that entered pipeline in period
• CNS was the therapeutic class with highest share of investigational drugs
• Top 10 firms terminated a higher share of their failures in Phase I
• Large molecule approval rates outpaced small molecules 2:1
• The Phase II to Phase III transition was biggest hurdle for all firms

Another conclusion?  By failing more products in Phase I, Top 10 companies can improve productivity (return) of their pipelines by not wasting more money on late failures.  This supports the "fail fast" mantra.  The data also supports contention that large molecules will contribute a greater percentage of future industry revenues.  Also, there is support that more Phase III failures are occuring -perhaps due to the more difficult therapeutic areas being attacked - CNS, oncology, etc.

Posted by Bruce Lehr September 10th 2010.

 

Roche Signs $637 M Deal with ReMynd for CNS Therapies

Roche has opened its pocket book again to reach a deal with Belgium's ReMynd.  ReMynd has novel therapies in development to inhibit a-synuclein in Parkinson's and tau neurotoxicity in Alzheimer's.  Obviously, these are two sexy, high-value areas that have proven to be very difficult to crack up until now by a myriad of companies.

Roche will pay ReMynd up to $637 M in milestone payments should its programs prove to be successful in the clinic.  ReMynd has six programs aimed at either Parkinson's or Alzheimer's in its pipeline, and two more aimed at diabetes.  See Fierce Biotech.

 

Posted by Bruce Lehr September 7th 2010.

Amyloid Smamyloid!

A good post from Derek Low In the Pipeline reporting on interview of Mark Smith, Case Western, in Forbes.  Dr. Smith is a long time opponent of the theory that amyloid is a cause of Alzheimer's disease. He has long argued that amyloid is actually a sign of the brain trying to protect itself and that therapies geared toward removing amyloid will actually make things worse.

The recent Lilly trial seems to add some marks to his side of the ledger.  Of course, several other anti-amyloid drugs (gamma secretase inhibitors) are being tested by major pharma companies as we speak in Phase II trials.  We shall see if these trials bear similar results to that experienced by Lilly.

In the meantime, Dr. Smith predicts the field will stick with apporaches aimed at reducing amyloid until more patients are treated with other modalities not aimed at reducing amyloid plaques.

Posted by Bruce Lehr August 24th 2010.

Alzheimer's Researchers Innovate With Data Sharing

Fierce Biotech has a feel good story this morning from the world of Alzheimer's research. It seems that a 2003 effort amongst the NIH, FDA, industry, universities and nonprofits to commit to sharing data on Alzheimer's biomarkers is PAYING OFF.

The project, called the Alzheimer's Disease Neuroimaging Initiative, is basically an open innovation effort where all parties share data in real time. By putting IP concerns aside, all parties have benefitted with greatly enhanced understanding of key biomarkers.  This in turn may lead to other diseases', like Parkinson's, adopting this approach. See we're advancing the field.

Posted by Bruce Lehr August 13th 2010.