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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FDA whacks Alexza Pharma with CRL for Adasuve

Posted under Adasuve, Alexza Pharmaceuticals, Blog, Companies, Diagnostics, FDA, Funding, loxaprine, Medical Devices, Medical Supply, Pharmaceuticals, Regulatory, schizophrenia, Startups, Universities, Videos by rmcbride

Alexza Pharmaceuticals ($ALXA) was dealt another blow in its pursuit to gain approval of Adasuve from regulators. The FDA shot down the company's latest application because of manufacturing deficiencies related to the device used to take the inhaled antipsychotic drug, the company revealed last night.

The drug developer's shares tumbled 32.8% to 41 cents per share in pre-market trading.

U.S. regulators denied the company's application for Adasuve--a quick-acting inhaled version of the old drug loxaprine for outbursts from schizophrenia and manic episodes--in a complete response letter (CRL). The FDA stated in the CRL that manufacturing deficiencies would have to be addressed before Adasuve could be approved. Executives tried to put a positive spin on the CRL, pointing out that no new safety or clinical issues cropped up in the letter. But as biotech commentator Adam Feuerstein indicated on Twitter, that doesn't tell investors whether regulators felt that the company had resolved previous safety concerns. 

Adasuve promises patients with schizophrenia and biopolar I the benefits of easy administration and fast activity of loxaprine, The Wall Street Journal reported. Yet the inhaled version of the drug has raised concerns about its potentially deadly pulmonary effects and the risks associated with improper use of the treatment. Despite those concerns, the drug narrowly passed muster late last year in an FDA advisory panel's 9-8 vote to back approval. Yet the glow from that small victory quickly vanished when the FDA said in January that its decision on approval would be delayed by three months.

Alexza executives plan to address the CRL in a conference call this morning, no doubt in an effort to reassure investors that a way forward exists for the troubled program. The CRL also brought up the issue of Adasuve's product labeling and a REMS plan that has been proposed to limit potential dangers of the treatment, yet the details of those items were murky in the company's release.

- here's the release
- see the WSJ report

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Biotech startup Mnemosyne snags $5.4M A round for neuropsych R&D

Posted under Blog, Companies, Diagnostics, Funding, Medical Devices, Medical Supply, Mnemosyne, Pharmaceuticals, schizophrenia, Startups, Universities, Videos by John Carroll

A fledgling biotech in Providence, Rhode Island has put together a $5.4 million A round to fund its plans to develop new treatments for neuropsychiatric disorders. Launched nearly two years ago with seed funding from the Slater Technology Fund and private investors, Mnemosyne has been focused on N-Methyl-D-Aspartate--or NMDA--receptor pharmacology.

Mnemosyne's scientific founders are pursuing a trail of evidence that suggests the NMDA receptor is the key to a range of neuropsychiatric conditions. And they're starting off with research that points to malfunctioning NMDA receptors as a prime suspect for schizophrenia. The round was led by Access BridgeGap Ventures with the Slater Technology Fund adding to its investment in the company.

"Completing the Series A financing will enable us to ramp up the pace of our discovery programs considerably," stated Kollol Pal, Ph.D., president and CEO.

Pal tells FierceBiotech that the Series A money should be enough to get the biotech to the stage where it has identified a lead small molecule for development. A Series B round can be raised to get into the clinic. And the first shot is likely to center on an NR2B potentiator, a subunit in the NMDA receptor area that its scientists--a group that includes the prominent Mark Bear, a professor of neuroscience at MIT and a Howard Hughes Medical Institute investigator--strongly believe has great potential as a treatment for schizophrenia.

The biotech is getting into early-stage neuropsych work at a time Big Pharma companies like GSK ($GSK), AstraZeneca ($AZN) and Pfizer ($PFE) have been dramatically slashing their own discovery work in the field. But Pal says that he's had no trouble getting companies interested in their work and the potential of an NR2B potentiator.  

"They say 'Come back to us when you have an interesting compound,' " says Pal. And now that's just what he intends to do. Like a lot of start-ups, Mnemosyne is big on concept and small on staff. Three employees are at the company now, says Pal, and a CRO is collaborating on development.

- here's the press release

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Alexza shares spike after antipsychotic wins weak embrace from FDA panel

Posted under Adasuve, Alexza Pharmaceuticals, Bipolar disorder, Blog, Companies, Diagnostics, Funding, Medical Devices, Medical Supply, Pharmaceuticals, schizophrenia, Startups, Universities, Videos by John Carroll

Alexza Pharma ($ALXA) just barely managed to clear one of the big hurdles that threatened to once again block its marathon effort at winning an FDA approval of the inhaled antipsychotic treatment Adasuve (formerly AZ-004). An expert FDA committee voted 9 to 8 in favor of an approval yesterday evening, with a number of critics clearly remaining unhappy with the safety issues that have hobbled the program before.

Just days ago investors were dumping shares in Alexza after reading regulators' concerns about the potentially lethal pulmonary effects of the treatment in patients with asthma or COPD. Those same risks persuaded the FDA to reject Alexza's initial try at an approval. But a majority of the FDA panel felt that the biotech's risk mitigation strategy, which would demand that patients are carefully screened and then monitored for the first hour after treatment, satisfied their safety concerns.

"This product offers the potential to be a significant contributor to an important need," noted Andrew Winokur, director of psychopharmacology at the University of Connecticut School of Medicine in Farmington, according to a report from Bloomberg. Alexza provided "impressive efficacy data."

Adasuve is a vaporized version of the old antipsychotic loxapine. Inhaling it with the use of a new device developed by Alexza offers a quick method for dealing with bouts of schizophrenia and bipolar mania. But a number of specialists in the FDA remain worried that the drug could wind up in the wrong hands, or administered without all the necessary precautions.

Investors, who have alternately fled and embraced Alexza's shares, initially responded to the positive vote by pushing its battered shares up more than 70%. By mid-morning some of those gains had been given up as analysts considered Alexza's chances at finally winning an approval from a skeptical FDA. Some analysts say an approval could pave the way to a market worth about $150 million in annual revenue.

Alexza now faces a PDUFA deadline on February 4.

- read the press release
- here's the report from Bloomberg

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