Today's Top News Monday, March 28, 2016 | By John Carroll
| | Alder CEO Randall Schatzman |
Alder Therapeutics ($ALDR) posted positive--and competitive--data for their Phase IIb study of a new CGRP drug for migraine, keeping it in the hectic race aimed at coming up with the first new drug approval in the crowded space. And investors responded by driving up Alder shares by 55% in early trading this morning. The Bothell, WA-based biotech says that their 300-mg and 100-mg doses of an intravenous injection of ALD403 reduced the average number of migraines 75% among 33% and 31% of the patients taking those two doses, respectively, hitting the primary endpoint in the trial. And the developer added that their data indicate that the drug can be given on a quarterly basis, making it competitive with some major league rivals in the field now positioning themselves for the market. Their two doses, along with a 30-mg group, also hit a secondary endpoint for an immediate and durable drop in migraine days from the start of the 12-week study period. And 8%, 5% and 4% of the 300-mg, 100-mg and 30-mg drug arms were free of migraines through the quarter. A 10-mg dose was judged subpar. "Evaluation of ALD403 continues to exhibit a potential best-in-class profile, which includes immediate, significant and durable migraine prevention with infrequent quarterly dosing," said CEO Randall Schatzman in a statement. "Today's data also support our quarterly dosing strategy via a single intravenous, subcutaneous or intramuscular injection. With our commitment to the accelerated development of ALD403 reinforced by today's positive results, we look forward to advancing our development plan, and assuming FDA approval, independently marketing ALD403 in the U.S. to meet the critical medical needs of the 13 million patients nationwide who are candidates for migraine prevention therapy." Little Alder is likely going to face some heavyweight competition with its drug. Teva ($TEVA) already posted positive Phase IIb data from their study of the CGRP therapy TEV-48125. Eli Lilly (LY2951742) and Amgen (AMG334) are also racing along with their own late-stage efforts, as everyone looks to drugs that target calcitonin gene-related peptide, or CGRP, a chemical involved in inflammation and pain signaling. As often happens in a Phase III showdown, the developers are already trying to position themselves with better dosing schedules and easier administration. To that end, Alder reported some encouraging bioavailability numbers for a subcutaneous version of their drug. But as ISI Evercore's Umer Raffat notes this morning, the data don't align neatly, as the developers produce a mixed bag of results on headache days, migraines and more, using different standards on the severity of the migraines being treated. "TEVA reported their data on a monthly basis," notes Jefferies' Brian Abrahams, "but averaging out the 50% and 75% responder rates for each month at TEVA's go-forward dose, the rates look generally comparable to what ALDR showed (16% and 14% for TEVA). Still, comparisons are limited by: 1) unknown differences in baselines (ALDR's patients may have been sicker); 2) Total quarterly dosing for TEVA in ph.II was ~4-12x higher than for ALDR at ALDR's potential quarterly SC doses; and 3) TEVA calculated their data slightly differently (reductions in moderate to severe headache days, vs. reduction in overall migraine days over the 12 weeks)." That will all be sorted out in Phase III now, as payers brace for a new generation of migraine drugs for a tough-to-treat affliction. - here's the release Related Articles:
Big Pharma pushes new migraine drugs into Phase III with blockbuster hopes
Alder hunts for a new partner after Bristol-Myers nixed a $1B deal
Shooting for IPO glory, Alder cites trial success with migraine drug
Friday, March 25, 2016 | By John Carroll
Acadia's regulatory and research crew will face some tough questions come Tuesday's FDA advisory committee review of its Parkinson's antipsychotic drug pimavanserin ($ACAD), but a scan of the agency's internal review document issued today suggests that the door is still open to a possible approval. The long-delayed FDA assessment acknowledges that the 34-mg dose of pimavanserin (Nuplazid) did significantly improve symptoms of Parkinson's. But regulators clearly red-flagged their safety concerns, noting a distinct increase in the number of deaths as well as adverse events among the patients taking the drug compared to the control arm of the study--even if there was no obvious clue what was triggering those events. Because of the safety issues, the agency in particular wants to have a discussion with the outside experts about the questionable meaningfulness of the clinical benefit of the drug. "While the applicant will present evidence that the treatment effect represents a clinically meaningful change," writes Mitchell Mathis, director of the division of psychiatry products, "the Division's medical officer will present his interpretation of the same data and reach a different conclusion." None of that seemed to spook investors, though. Acadia's shares shot up 25% in early trading on Monday. Analysts have pegged 2020 revenue from Nuplazid at $1.4 billion, making this one of the top drug prospects up for review this year. The FDA has designated the therapy as a "breakthrough" drug warranting a quick response from regulators. "Serious adverse events (AEs) occurred in 16/202 (7.9%) patients taking pimavanserin 34 mg versus 8/231 (3.5%) placebo-treated patients" in the studies, noted the FDA review. And it was also clear to the regulators that the rate of AEs increased with the dosage of the drug. But that's also not necessarily damning. This is a patient population, after all, that suffers a high mortality rate, as well as adverse events. The regulators were also unable to explain the differences. States the FDA: "As with the disproportionate increase of serious adverse events in the pimavanserin 34 mg daily group compared to the placebo group, there is no obvious unifying pathophysiologic process or unique adverse event that drives or dominates this disproportion." Side effects and increased mortality rates among Parkinson's patients taking antipsychotic meds is common, though, as a new study from investigators at the University of Pennsylvania has just pointed out. Looking over VA records on some 15,000 Parkinson's patients, the researchers found that patients starting on the drugs were twice as likely to die over the next 6 months compared to a similar patient group who stayed off drugs. Another concern San Diego-based Acadia will face on Tuesday: The review noted that the agency only has one positive trial to consider in making a decision on the drug, even though it typically would require at least two positive studies. That, also, was not presented as a deal killer by the FDA reviewers. Like many other FDA reviews, the regulators in this case wanted to highlight the weaknesses in Acadia's case. But they accomplished that without sounding the kind of alarm that usually signals an odds-on rejection by the outside experts. This review will center on a risk/benefit analysis where there is no obvious outcome. And that should make Tuesday's panel review all the more interesting, as Acadia has a lot riding on the vote. - here's the review (PDF) Related Articles:
Acadia finally delivers long-delayed application for 'breakthrough' Parkinson's drug
Acadia craters as takeover buzz is silenced by (another) NDA delay, CEO exit
Acadia's shifting calendar spurs market-moving takeout rumors
Acadia surges after nabbing 'breakthrough' title for late-stage Parkinson's drug Friday, March 25, 2016 | By John Carroll
| | Forum CEO Deborah Dunsire |
Forum Pharmaceuticals' rare, high-risk strategy to launch ambitious late-stage trials for schizophrenia with a single major investor has ended in failure, triggering a company-wide reorganization. And with a companion Phase III program for Alzheimer's on indefinite hold at the FDA, the Waltham, MA-based biotech is hinting that its options for staying in business are dwindling. The company announced on Thursday that encenicline (FRM-6124) had failed its two co-primary endpoints for function and cognition in two Phase III trials that had recruited some 1,500 patients. The Boston Business Journal reports that Forum has already notified state officials of plans to ax 77 jobs--about half of its workforce--with another 12 on the chopping block based on their study results. In their statement the company said that it needed to "appropriately scale its spending and resources and to evaluate a potential path forward, if any." Stephen Knight, a partner at F-Prime Capital (until recently known as Fidelity Biosciences) recruited ex-Millennium chief Deborah Dunsire to run the high-profile effort at Forum about two years ago. She told me at the time that it was exciting to steer a company like Forum into big Phase III studies for a pair of tough targets like schizophrenia as well as Alzheimer's, which has defied the efforts of a long lineup of contenders over the past decade. Their drug is designed to enhance synaptic transmission in the brain by sensitizing the alpha-7 nicotinic receptor, improving cognition in patients. But the company says the drug was defeated in the schizophrenia studies by a high placebo response. The FDA still has the Alzheimer's side of the program on hold after a "small" number of patients taking the drug reported severe gastrointestinal events last fall. Alzheimer's and big Phase III studies like this cost hundreds of millions of dollars to pull off, which is why a small biotech and single primary investor would almost never take on the risk alone. Typically it's giants like Eli Lilly ($LLY), Johnson & Johnson ($JNJ) and Roche ($RHHBY) that dominate the late-stage cognition field. Now Forum has just as big a failure, but none of the resources needed to withstand a setback of this magnitude. Related Articles:
The FDA eases up on Forum's schizophrenia program with Alzheimer's trials still on hold
Feds clamp a hold on Forum's PhIII Alzheimer's study following GI events Monday, March 28, 2016 | By John Carroll
Shares of San Diego-based Apricus Biosciences ($APRI) were crushed this morning after the biotech reported that its experimental testosterone-boosting drug had failed both the primary and secondary endpoints in a Phase IIb study among men with secondary hypogonadism and sexual dysfunction. And the setback raises some additional issues for the entire drug class. Researchers noted that fispemifene at 450 mg did boost testosterone among the men in the study, but failed to improve erectile function or low libido, missing out on providing a clear clinical benefit--an urgent necessity in the wake of the FDA's increased vigilance on testosterone therapies. As a result, the biotech plans to bury the program and focus on other work. The biotech's shares were routed on the news, plunging by about half. The drop left the company's shares in penny stock territory. "We are obviously disappointed with these results," said Apricus CEO Richard Pascoe. "As a consequence of these results, we will discontinue all development of fispemifene in symptomatic secondary hypogonadism, and focus our resources on our other homegrown pipeline assets." Testosterone replacement therapies have come under scrutiny at the FDA, where regulators have grown increasingly alarmed at the prospect of the overuse of the treatments, worried about evidence of increased risk of heart attacks and strokes. As a result, regulators have sought to limit treatment to a narrow group of patients who would clearly benefit from their use. After the FDA rejected Repros' testosterone therapy recently, Apricus says it affirmed its study design on fispemifene with regulators, centering on clinical benefit measures. That raised regulatory bar will likely plague other developers in the field. And Apricus signaled that their failure could have significant implications for the class. "While we did see statistically meaningful changes in testosterone levels into the low normal ranges with fispemifene, the compound's ability to increase those levels sufficiently to demonstrate clinical benefit is limited, and may be an issue with the entire SERM class," said Dr. Barbara Troupin, chief medical officer of Apricus. "The regulatory benchmark for approval of a compound in secondary hypogonadism in men is the achievement of a symptomatic clinical benefit, using patient-reported outcome measures in a defined patient population. Achievement of biochemical or PK normalization of testosterone into the low normal range is not sufficient for regulatory purposes." - here's the release Related Article:
Quality issue keeps Apricus Biosciences from getting Swiss approval for Vitaros Monday, March 28, 2016 | By Ben Adams
Dr. Reddy's Laboratories ($RDY) has signed a $490 million drug licensing deal with California's XenoPort ($XNPT) as the struggling biotech looks to shed its R&D ahead of a rumored sale of the company. Hyderabad, India's Dr. Reddy's will be granted exclusive U.S. rights for the development and commercialization of XenoPort's oral new chemical entity, XP23829. The generic, drug development and manufacturing firm said it now plans to develop XP23829 as a potential treatment for moderate-to-severe chronic plaque psoriasis--and may also develop XP23829 for relapsing forms of multiple sclerosis, as it has a similar mechanism of action as Biogen's ($BIIB) marketed MS drug Tecfidera. Dr. Reddy's will hope to have better success with the treatment than XenoPort after it posted mixed results for the drug in a Phase II study for psoriasis last year. The CA-based company initially declared the trial a success and outlined plans for a late-stage effort--but later relented and cut the program altogether. In October, the biotech also announced plans to lay off 25 workers, while its CEO Ronald Barrett--who helped start the company in 2009--announced his imminent retirement. Under the deal, XenoPort will receive a $47.5 million up-front payment and an additional $2.5 million for transfer of certain clinical trial materials to Dr. Reddy's Laboratories. It could also get up to $190 million if it hits certain regulatory targets, on top of which it may gain a further $250 million if it also reaches key commercial milestones. Dr. Reddy's has in addition promised to pay up to mid-teens royalties if things go really well, meaning it could take $490 million-plus from the deal. Raghav Chari, executive VP of the Proprietary Products Group at Dr. Reddy's Laboratories, said: "XP23829 complements our internal development efforts, which have primarily focused on the mild-to-moderate psoriasis segment to date. "In other markets, fumarates have been used as first-line choices of treatment prior to initiation of biologic therapies in patients with moderate-to-severe psoriasis. We intend to initiate the registration program for XP23829 as soon as feasible so that we can accelerate the availability of this important treatment choice for moderate-to-severe psoriasis patients in the U.S. market." XenoPort said earlier this year it was looking to sell off its entire R&D portfolio--its only other remaining candidate is the mid-stage Parkinson's disease treatment XP21279. At the start of the year, Reuters reported XenoPort was in fact looking to sell itself completely--and this latest deal looks like it may still be heading in that direction. XenoPort has just one approved asset to date: the restless legs syndrome treatment Horizant and has put all of its efforts behind this drug. It was first approved in 2012 but quickly turned out to be a sales disappointment, with partner GlaxoSmithKline ($GSK) abandoning its stake in Horizant shortly after launch. The biotech has since begun a trial for the drug as a potential treatment for patients with alcohol use disorder. New CEO Vincent Angotti said in a statement that his firm was now "fully focused on our Horizant commercialization effort," but did not disclose any further details about the biotech's future. - check out the release Related Articles:
Dr. Reddy's grows U.S. sales even in face of FDA action
Struggling XenoPort could be sold Sunday, March 27, 2016 | By John Carroll
| | Emulate CSO Geraldine Hamilton |
The investors behind Emulate say now's the time to move their organs-on-a-chip tech to the proverbial next level, offering a $28 million B round fashioned to fuel a marketing drive and more than double the size of its staff as it gets disruptive with preclinical R&D. The preclinical drug testing world is ready for the plug-and-play stage of organs-on-chips, says president and CSO Geraldine Hamilton about the Harvard spinout. Emulate is ready to start handing over the instrumentation and software necessary to make their products a regular feature in industry as well as academic labs. And they're getting the added financial backing from the Swiss billionaire Hansjörg Wyss, LabCorp (parent company of the big CRO Covance), NanoDimension, Cedars-Sinai Medical Center, OS Fund, Atel Ventures, and new investor ALS Finding a Cure. Hamilton says the company expects to see its workforce swell over the next year, using the new funds to grow from 40 to about 85 staffers to help drive marketing efforts. And the extra cash will also be used to expand its offerings of small, chip-based organ substitutes for lung, liver, intestine, and skin with new systems for the kidney, heart, brain and more. Hammered out at the billionaire founder's namesake Wyss Institute, Emulate's tech will be used first to augment and then one day perhaps succeed the animal testing that has long been the gold standard for testing drugs before they are tried in human trials. The scientific currency of that gold standard, though, has long been debased by a history of unreliability. Only a tiny fraction of what's successfully tested in animals--and frequently touted in headlines around the world--winds up as a new treatment on the market. Mice, for example, can make for poor models of human biology, often failing to transmit the complex safety and efficacy signals needed to see if researchers are starting down the right track. Emulate's organs-on-chips could help improve the odds, or at least help winnow out future failures earlier. And with the controversial economics of drug development dominated by talk of billion dollar-plus costs for clinical stage development at the industry giants, the fledgling Emulate expects to be helped by more industry collaborations like the pioneering pact it struck with J&J. "This really positions us to go to next stage of growth," says Hamilton, who will now start looking to the rank-and-file players in preclinical work to help establish the chip technology. The chips are especially helpful in looking at a drug's mechanisms of action, she adds. But plenty of hurdles remain for the technology adoption to take place. The FDA still relies on animal testing to establish a safety baseline on drugs. And in some fields, like immuno-oncology and metabolics, animal testing is particularly weak--fields in which Emulate can look to make early inroads. Even in cases where primates are used as the industry standard, as in infectious diseases, the chips can provide a much less expensive, earlier inspection of a drug's potential. Hamilton's not committing to any particular timeline for profitability. But she and her investors believe the time is ripe to give the tech--and their dream--a shot at it. - here's the release Related Articles:
J&J teams with Emulate to use organ-on-a-chip technology in R&D programs
J&J details a slew of early R&D partnerships--including at least 5 in med tech Monday, March 28, 2016 | By Ben Adams
The metalloproteins specialist Forge Therapeutics and Active Motif, which develops tools to help "turn off" certain genes, have penned a new deal in epigenetic research. The two biotech companies--both based in California--said in a statement they aim to validate emerging epigenetic targets in cancer and demonstrate the drugability of the family of iron-containing lysine demethylases known as Jumonji KDMs. The research collaboration--financial details of which were not disclosed--will combine Forge's expertise in the field of metalloenzymes and Active Motif's experience in epigenetics and related technologies. "Other epigenetic targets such as histone deacetylases and methyl transferases have been validated therapeutically, however the Jumonji KDM family has been lagging behind due to a lack of suitable chemistry and limited biological tools available to early-stage companies," said Zachary Zimmerman, CEO of Forge Therapeutics. "The Forge drug discovery engine has generated several full length inhibitors that are selective and potent for individual KDMs and subfamilies of KDMs, and we look forward to probing epigenetic biology using Active Motif's suite of technologies." Cancer, autoimmune and neurological disorders can all be caused by abnormal epigenetic activity and may be helped by "turning off" related genes that are causing a disease. In fact, some companies are already doing this, with Celgene ($CELG) leading the way with its blood cancer drug Vidaza and T-cell lymphoma treatment Istodax. And just last week Google's funding arm GV also backed a new Cambridge epigenetics spinoff in a $21 million funding round. Historically, methylation of Arg and Lys residues has been considered a stable, irreversible process due to the slow turnover of methyl groups in chromatin. But the discovery in recent years of a large number of histone Lys demethylases (i.e., KDMs, belonging to either the amino oxidase or the JmjC family) completely changed this point of view and suggested a new role for dynamic histone methylation in biological processes. Since overexpression, alteration, or mutation of a number of KDMs has been found in many types of cancers, such enzymes could represent diagnostic tools as well as epigenetic targets to modulate for obtaining novel therapeutic weapons against cancer. A recent report by Citigroup estimates that the epigenetic oncology market could be worth around $10 billion a year by 2025. Joseph Fernandez, CEO of Active Motif, added: "Active Motif's expertise in epigenetic research tools and complex epigenetic analysis combined with the prowess of Forge Therapeutics to quickly generate compounds that specifically inhibit epigenetic modifying proteins positions this collaboration to become a preeminent epigenetic drug discovery effort. This cutting-edge research aims to help advance novel therapeutics for oncology indications." - see the release Related Articles:
Google backs Cambridge epigenetics spinoff in a $21M round
Merck bets up to $515M on an epigenetic project for cancer and blood disease | Sponsored Content | | By Maggie Gunther From start-ups to leading global companies, Greater Fort Lauderdale provides a stimulating and supportive business environment for success in the life sciences. Allergan, Stryker and Teva are among the major medical device, biomedical, pharmaceutical and clinical research companies with R&D, manufacturing and distribution facilities in Greater Fort Lauderdale. South Florida is home to one of the nation's most dynamic industry clusters with convenient access to leading research institutes and academic institutions. To the north are Scripps Florida, Max Planck Florida Institute, and Torrey Pines Institute for Molecular Studies. In Greater Fort Lauderdale – a longtime home for many biomedical companies – Nova Southeastern University is expanding its life science research facilities, and the University of Miami's Miller School of Medicine is investing in its biomedical research and commercialization programs. The region's academic institutions, research parks and economic development organizations have joined together to form Life Sciences South Florida. BioFlorida is the voice of Florida's life sciences industry with regional chapters that represent nearly 5,500 establishments and research organizations in the biotechnology, pharmaceuticals, medical devices/diagnostics and bioagriculture sectors. BioFlorida's initiatives provide a strong business climate for the advancement of innovative products that improve lives and promote economic benefits to the state.
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