Genentech drug picked for pioneering $100M Alzheimer’s trial

Posted under Alzheimer's, bapineuzumab, beta amyloid, Blog, Companies, crezenumab, Diagnostics, Funding, Genentech, Medical Devices, Medical Supply, NIH, Pharmaceuticals, Pipeline, semagacestat, solanezumab, Startups, Universities, Videos by john

The NIH has agreed to help bankroll a pioneering $100 million study of Genentech's experimental Alzheimer's therapy crenezumab. Investigators will test the drug in a region of Colombia where a particular genetic mutation is known to trigger the early onset of Alzheimer's, with an eye to determining if they can stop the memory-wasting ailment before it starts.

The NIH has agreed to pay for $16 million of the study, with private donors putting up $15 million more and Genentech adding the rest--about $65 million--to bankroll the effort. The announcement is part of an ambitious effort announced Tuesday to find an effective treatment for the disease by 2025 in the hopes of thwarting a steadily growing epidemic of Alzheimer's as the baby boomer generation turns gray and old.

The news is a coup for Genentech, which had one of 25 therapies considered for the public/private study. Like a number of other therapies in the pipeline, crenezumab targets the toxic protein beta amyloid, which accumulates in the brain of Alzheimer's victims. But while amyloid remains a prime suspect in the disease, investigators have yet to determine whether eliminating or reducing the levels of toxic material is a safe and effective approach to treating the illness.

Earlier attempts to target beta amyloid have met with failure, if not outright disaster, as was the case with Eli Lilly's ($LLY) semagacestat. But in a common strategy, investigators have been testing the treatments in patients with advanced cases. In this instance, the drug will be studied in patients who have yet to see the disease develop to the point where it has already wreaked havoc on the brain. Investigators also believe that crenezumab may be less likely to cause tiny brain hemorrhages which can afflict patients. The drug is currently in mid-stage testing after completing positive early-stage groundwork.

"This will be the first test of an anti-amyloid treatment in a preclinical stage, where it has the best chance to have the most profound benefit," Dr. Eric Reiman, executive director of Banner Alzheimer's Institute, told reporters today. Banner is leading the study.

Two other drugs, bapineuzumab and solanezumab, are in late-stage studies that wrap this summer. Analysts have generally been skeptical of the outcomes, noting the deep uncertainties that surround the disease and past failures.

The news is also a boon to AC Immune, a Swiss company which partnered with Genentech on the program back in 2006.

- get the story from Reuters
- here's the article from The New York Times

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Big Pharma’s high-risk pursuit of CNS gold faces major market doubts

Posted under Alzheimer's, Big Pharma, Blog, CNS, Companies, Diagnostics, Eli Lilly, Funding, gantenerumab, ISI Group, Johnson & Johnson, Medical Devices, Medical Supply, neuroscience, Pfizer, Pharmaceuticals, Pipeline, Roche, schizophrenia, semagacestat, solanezumab, Startups, Universities, Videos by john

Here's an interesting number for anyone interested in the risks and rewards of drug development: Two of every three analysts and fund managers recently queried by the ISI Group say they expect that new Alzheimer's drugs in late-stage testing at Eli Lilly and Pfizer/J&J will fail. 

The poll comes up in a broad look at Big Pharma's relentless pursuit of CNS gold by Bloomberg. The story starts off with a look at Roche's ($RHHBY) central nervous system picks, which include a mid-stage Alzheimer's drug as well as a shot at schizophrenia. Analysts have been pushing Roche to show that it can succeed in developing new drugs outside of the cancer arena. And the stakes spiked considerably last week when Roche tanked its high profile cholesterol drug after it failed to register efficacy in Phase III.

Drawn by the prospect that even a modest success against a disease like Alzheimer's will deliver Lipitor-sized rewards for years to come, pharma companies have been diving ever deeper. In Lilly's ($LLY) case, the push to complete a late-stage program for solanezumab follows the failure of semagacestat. But this time around Lilly says it has a better understanding of the disease. And Roche has ventured into the same arena, with four of its 10 brain drugs focused on treating the memory-wasting disease. Its Alzheimer's program--gantenerumab, which reduced amyloid in a small study--is now in mid-stage testing.

Not all pharma outfits are as bullish. Big setbacks in depression prompted AstraZeneca ($AZN) to restructure its CNS division, downsizing its staff and looking for outside partners to share the risk. GlaxoSmithKline ($GSK) famously decided to stay away from high-risk CNS drugs several years ago. And fresh reversals later this year could prove an even more painful setback for the field, where the high failure rate may force other companies to change tactics as well. 

"The central nervous system will remain the highest of the high-hanging fruit," Citigroup's Andrew Baum tells Bloomberg. And fewer hands will be reaching for it if the market turns even more skeptical about the odds of this game. Lilly, for one, is already in a weak position with one of the industry's weakest late-stage pipelines. Another blow could force major changes.

- here's the article from Bloomberg

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Pfizer turns to late-stage pipeline to make up for Lipitor crash

Posted under Alzheimer's, Alzheimer's disease, bapineuzumab, Blog, Companies, Diagnostics, Eliquis, Funding, Lipitor, Medical Devices, Medical Supply, Pfizer, Pharmaceuticals, Startups, tofacitinib, Universities, Videos by john

As expected, Lipitor sales are being blasted by generic competition in the U.S. And with Pfizer's ($PFE) sales numbers plunging, the pharma giant is staying focused on the fate of a trio of late-stage therapies that are desperately needed to fill a growing gap.

For the record, Lipitor sales in the U.S. dropped 71% in the first quarter. But Pfizer is betting that after years of pipeline snafus and bad deal-making strategies, it can demonstrate once and for all that it has turned the corner on a smarter, more focused development approach.

The three main characters in that story line are tofacitinib, a potential blockbuster for rheumatoid arthritis with an August PDUFA date, the anti-clotting drug Eliquis, up for a decision in June, and the high-risk Alzheimer's Phase III studies for bapineuzumab.

Some analysts have been fretting over safety issues for tofacitinib, as Dow Jones' Peter Loftus reports. But many still expect it to fare well at the FDA, which is an experienced hand at considering the risk/benefits of new RA treatments. Eliquis, meanwhile, is widely considered an odds-on favorite for an approval. The wild card is bapineuzumab, partnered with Johnson & Johnson. According to Dow Jones, Pfizer expects late-stage data in the summer. But TheStreet's Adam Feuerstein tweeted this morning that the first Phase III trial is finished but Pfizer wants to wait until the second study is completed later in the year before releasing data. 

For Feuerstein, one of many Alzheimer's skeptics who have seen a series of R&D fiascos in the space, that's an ominous sign. A number of analysts note that an approval would be worth billions, but the odds of success are slim. A pair of regulatory wins ahead of the data release, though, would soften any blow from a bapi failure.

- here's the story from Dow Jones

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Elan chases a holy grail of Alzheimer’s treatment: Prevention

Posted under Alzheimer's, bapineuzumab, beta amyloid, Blog, Cambridge University, Companies, Diagnostics, Drug Discovery, Elan, Funding, Medical Devices, Medical Supply, Pharmaceuticals, R&D, Startups, Universities, Videos by rmcbride

After struggles to develop an effective remedy for Alzheimer's disease, Elan's ($ELN) support of research at Cambridge University could unlock targets for a drug that offers a preventive treatment for the memory-stealing disease and other illnesses involving misfolding proteins in the brain. 

While the findings are very early-stage, an investigator from Cambridge University has used nuclear resonance imaging and computer modeling to capture the misdeeds of a protein known as beta amyloid, which forms into clumps in the brains of Alzheimer's patients. And the research could yield targets and lead to drugs that act on the proteins at the point at which they are about to turn bad and form into clumps associated with the disease, according to a Bloomberg report.

Michele Vedruscolo, the Cambridge University biophysicist working with Elan, published her findings in Science. The study shows the minute steps in the process of protein malformation with unique detail, shining new light on potential openings for drugs to intercede before the plaques form. In concept, a drug that could prevent the hallmark plaques associated with Alzheimer's would be akin to the benefits of statins such as Pfizer's ($PFE) Lipitor, which acts on an enzyme linked with formation of heart attack-associated cholesterol. What's more, the imaging technique used in Vedruscolo's study could detail the activity of another bad-acting proteinsin Alzheimer's called tau, Bloomberg reporter Elizabeth Lopatto told me via Twitter.

"This is potentially a game changer for drug discovery," Dale Schenk, Elan's chief scientist, wrote in an email to Bloomberg. "We look forward in the future to applying the principles described in this work to other proteins."

Of course, this could all amount to nothing for patients. Theories about ways to combat Alzheimer's have often failed to hold true in clinical trials, as Elan and other companies such as Eli Lilly ($LLY) have learned with earlier programs that fell short. Yet with a dearth of effective drugs against the disease, which affects more than 5 million people in the U.S. alone, any drug with a relatively clean safety profile and a modicum of efficacy could bring incredible riches to its developers.  

Ireland-based Elan has a sizable stake in Alzheimer's drug development. After selling most of its rights to an antibody against the disease to a Johnson & Johnson ($JNJ) unit, Elan retains a quarter of the rights to the potential blockbuster known as bapineuzumab, which J&J and partner Pfizer have in late-stage development. The Phase III data on the program are expected later this year, with the fate of the drug having potential multibillion-dollar implications for its owners.

- read the Bloomberg article

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