Teva to Buy Auspex Pharmaceuticals for $3.2 billion

Teva Pharmaceutical Industries has purchased Auspex Pharmaceuticals after an offer for all of the outstanding shares of Auspex at $101.00 per share in cash, representing total consideration of approximately $3.2 billion in enterprise value and approximately $3.5 billion in equity value. 

Teva hopes the transaction will enhance revenue and earnings growth profile and strengthen its core central nervous system CNS franchise with the addition of Auspex's portfolio of movement disorder medicines.

The company describes Auspex as “a biopharmaceutical company specializing in applying deuterium chemistry to known molecules to create novel therapies with improved safety and efficacy profiles.” Its lead investigational product, SD-809 (deutetrabenazine) leverages Auspex's deuterium technology platform and is being developed for the potential treatment of chorea associated with Huntington's disease, tardive dyskinesia, and Tourette syndrome, with a pharmacokinetic profile that allows for lower doses.

Transaction Highlights Per TEVA

  • Strategic fit – strengthens Teva's leadership position within CNS and expands presence into underserved movement disorder markets
  • Teva's existing capabilities and infrastructure in CNS are expected to accelerate the potential for SD-809 and Auspex's additional pipeline assets
  • Near-term value creation – SD-809 for Huntington's disease is expected to be approved and launched commercially in 2016
  • SD-809 is currently in Phase 3 for tardive dyskinesia and Phase 1 for Tourette syndrome
  • SD-560 (deuterated pirfenidone) is currently in development for idiopathic pulmonary fibrosis

Study: Use of Anti-Clotting Drug More Than 3 Hours After Stroke Should Be Re-evaluated

Advice to use the anti-clotting drug alteplase more than three hours after an acute stroke should be re-evaluated, say researchers writing in the British Medical Journal (BMJ).

Most major stroke guidelines support use of alteplase up to 4.5 hours after stroke onset, but Dr. Brian Alper and colleagues believe that current guidance is based on uncertain evidence and they call for urgent reconsideration of the available data to guide policy decisions.

Researchers examined comprehensive sources of evidence and advice, including American Heart Association and American Stroke Association guidelines, a 2014 Cochrane review, and a 2014 meta-analysis of individual patient trial data. Each of these sources suggests that alteplase is more beneficial than harmful when given 3-4.5 hours after the onset of ischaemic stroke.

The researchers analyzed the data supporting these conclusions and found inconsistent evidence on the effects of alteplase at 3-4.5 hours after stroke.

For example, some data support an increase in good functional outcome at three months, and others show a worse functional outcome at six months. As such, any single estimate of effect from currently available data is therefore likely to be unreliable, they write.

The authors acknowledge this may not “settle” the issue, but conclude: “Unless and until there are data showing unequivocal benefits to outweigh known harms, we believe that there should not be any strong recommendation or encouragement for use of alteplase beyond three hours after stroke.”

Blood Test Can Help Identify Stroke Risk Following Heart Surgery

The results of a blood test done immediately after heart surgery can be a meaningful indicator of postoperative stroke risk, according to a new study out of Wake Forest and published in the March online issue of the Annals of Thoracic Surgery.

An acutely elevated level of blood urea nitrogen (BUN)—a measure of kidney function detected through blood testing—was the most powerful predictor of postoperative stroke among the study's subjects.

Up to nine percent of cardiac surgery patients suffer post-operative stroke, and these events are significantly more serious and more frequently fatal than those experienced in the general population.

In the case-controlled study, researchers analyzed nearly 5,500 adults 18 to 90 years old who underwent cardiac surgery from 2005 to 2010 and identified 180 who suffered a stroke within 10 days of surgery. An elevated BUN level was not only the most accurate predictor of stroke in this group, it greatly exceeded the predictive accuracy of more commonly recognized risk factors such as smoking, pre-operative high blood pressure and emergency surgery.

The test that measures BUN is inexpensive and routinely administered before and after all cardiac surgeries, researchers say. However, the test is most effective as a predictor for stroke if it is administered immediately after surgery rather than at the discretion of the physician, which is the current practice, said Martinson K. Arnan, assistant professor of neurology at Wake Forest Baptist and lead author the study.

“Based on our research, we need to more carefully monitor patients with high BUN postoperatively for any symptoms of stroke so that they may benefit from therapy immediately,” he said. “Anything that can help us better assess that risk can help decrease the incidence of stroke, decrease disability and reduce expenses.”

Drug For Opioid-induced Constipation Meets Phase III Endpoints

Naldemedine met its primary and secondary endpoints in a phase III study (COMPOSE I) for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain receiving opioid therapy, according to Shionogi, the drug's maker.

Naldemedine is an investigational peripherally acting mu-opioid receptor antagonist (PAMORA).

Study results showed that naldemedine (0.2mg tablet given once daily) statistically significantly improved the frequency of spontaneous bowel movement (SBM) compared with placebo over 12 weeks. Naldemedine was generally well-tolerated with the most commonly reported side effects being gastrointestinal disorders. This is the first phase III data generated from the COMPOSE program.

The COMPOSE program is a global comprehensive development program comprised of 7 clinical studies being conducted in patients with OIC with cancer or chronic non-cancer pain. 

COMPOSE I is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The study was designed to evaluate the efficacy and safety of naldemedine therapy, versus placebo, in 547 patients receiving chronic opioid therapy, who experience OIC accompanied by chronic non-cancer pain.

Meta-analysis: Dementia Screening Tool More Useful in General Setting

A new meta-analysis suggests that the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) performs better in the general hospital setting than in the specialist memory setting. The research was published online March 10 in The Cochrane Database of Systematic Reviews.

Ultimately, the authors conclude the IQCODE can be used to identify older adults in the general hospital setting who are at risk of dementia and require specialist assessment, and that it is useful specifically for ruling out those without evidence of cognitive decline.

The IQCODE is a questionnaire instrument that requires an “informant” who knows the patient well to rate cognitive change over time on a 5-point likert scale in an attempt to identify dementia. The authors note that in secondary care, there are two specific instances where patients may be assessed for the presence of dementia: in the general acute hospital setting, where opportunistic screening may be undertaken, or in specialist memory services where individuals have been referred due to perceived cognitive problems. 

For the analysis, authors whittled down 72 possible studies describing IQCODE test accuracy to 13, representing data from 2745 individuals (51% with dementia). The “secondary care” setting included all studies that assessed patients in hospital (e.g. acute unscheduled admissions, referrals to specialist geriatric assessment services etc.) and those referred for specialist ‘memory' assessment, typically in psychogeriatric services.

Researchers found a statistically significant difference in test accuracy between the general hospital setting and the specialist memory setting (P = 0.019), suggesting that IQCODE performs better in a ‘general' setting. Additionally, they saw no significant differences in the test accuracy of the short (16-item) versus the 26-item IQCODE, or in the language of administration, which supports the cross-cultural use of the tool.

They reported significant heterogeneity in the included studies, including a highly varied prevalence of dementia (10.5% to 87.4%). “Across the included papers there was substantial potential for bias, particularly around sampling of included participants and selection criteria, which may limit generalizability,” they write. “There was also evidence of suboptimal reporting, particularly around disease severity and handling indeterminate results, which are important if considering use in clinical practice.”

“Exploding Head Syndrome” Affects More Young Than Thought

An unexpectedly high percentage of young people experience “exploding head syndrome,” a psychological phenomenon in which they are awakened by abrupt loud noises, even the sensation of an explosion in their head, researchers say.

Researchers from Washington State University found that nearly one in five—18 percent—of college students interviewed said they had experienced it at least once. They also found that more than one-third of those who had exploding head syndrome also experienced isolated sleep paralysis.

The study is the largest of its kind, researchers say, with 211 undergraduate students interviewed by psychologists or graduate students trained in recognizing the symptoms of exploding head syndrome and isolated sleep paralysis. The results appear online in the Journal of Sleep Research.

Based on smaller studies, some researchers have hypothesized that exploding head syndrome is a rare condition found mostly in people older than 50. “I didn't believe the clinical lore that it would only occur in people in their 50s,” said Brian Sharpless, one of the researchers and a Washington State University assistant professor and director of the university psychology clinic. “That didn't make a lot of biological sense to me.”

The disorder tends to happen as one is falling asleep and may stem from problems with the brain “shutting down.” But instead of shutting down properly, the auditory neurons are thought to fire all at once, Sharpless said. It can last just a few seconds but can lead some people to believe that they're having a seizure or a subarachnoid hemorrhage, he added.

Repurposed Experimental Cancer Drug Investigated for Alzheimer's

A compound originally developed to treat cancer potentially could be used to treat Alzheimer's disease, new research suggests.Researchers demonstrated that the saracatinib restores memory loss and reverses brain problems in mouse models of Alzheimer's, and now are testing saracatinib's effectiveness in humans. The study was funded by the National Institutes of Health as part of an innovative crowdsourcing initiative to repurpose experimental drugs.

Researchers from the Yale University School of Medicine, conducted the animal study, published for early view on March 21 in the Annals of Neurology External Web Site Policy, with support from the National Center for Advancing Translational Sciences (NCATS) through its Discovering New Therapeutic Uses for Existing Molecules (New Therapeutic Uses) program. Launched in May 2012, this program matches scientists with a selection of pharmaceutical industry assets that have undergone significant research and development by industry, including safety testing in humans, to test potential ideas for new therapeutic uses.

Through NCATS' New Therapeutic Uses program, Yale neurobiology researcher, neurologist and senior author of the study Stephen Strittmatter, MD PhD, and colleagues obtained saracatinib (AZD0530), which the biopharmaceutical company AstraZeneca previously developed to treat cancer. Strittmatter and his team knew from previous studies that a protein called Fyn kinase plays a central role in how amyloid beta clusters damage brain cells. Saracatinib targets the same Fyn protein and already had cleared several key steps in the development process, giving Strittmatter's team a critical head start on the research.

“The investigational drug already had been developed, optimized and studied in animals as well as tested for safety in humans, so our ability to obtain this asset through NCATS and AstraZeneca gave us an incredible shortcut in the drug development process,” Strittmatter explained.

Effort Focuses on Migraine in Children

Although migraine in children can have a major impact on their health, school performance, family and social lives, kids who experience the condition often come up against barriers to getting help, specialists warn.

“Young migraine sufferers endure the same obstacles to getting relief from their pain as older migraine sufferers, including not having their pain taken seriously,” says American Migraine Foundation Chair David W. Dodick, MD, FRCP (C), Professor of Medicine at the Mayo Clinic College of Medicine in Scottsdale, AZ. “Many myths and beliefs persist in our culture that make it difficult to get a proper diagnosis and treatment.”

Dr. Dodick points out that even those with migraine themselves tend to downplay the impact of the pain on their lives and families. Those around them, including family members, may also unwittingly set up barriers to help.

Physicians may also dismiss a child's head pain.

Working with Phoenix Children's Hospital pediatric neurologist/headache specialist Marcy E. Yonker, MD, the American Migraine Foundation has added a range of resources and information on migraine in children to its website: http://www.americanmigrainefoundation.org. n

FDA ACTIONS

FDA Fast Tracks Drug for Duchenne Muscular Dystrophy

FDA has granted Fast Track designation for Santhera's Raxone/Catena (idebenone) for the treatment of Duchenne Muscular Dystrophy (DMD). 

FDA's Fast Track program facilitates the development and review of important drugs intended to treat serious conditions and fill an unmet medical need for the purpose of getting them to the patient earlier. Santhera previously announced that the Phase III trial (DELOS) in DMD met its primary endpoint and demonstrated that Raxone/Catena delayed the loss of respiratory function.

“On the basis of the positive data from our Phase III trial with Raxone/Catena in DMD we have started to prepare a New Drug Application and plan to meet with the FDA in the coming weeks to discuss our NDA dossier in a pre-NDA meeting,” said Thomas Meier, PhD, CEO of Santhera.

FDA Lifts Breaks on Pain Drug Study

Pfizer and Eli Lilly are preparing to resume the Phase III clinical trial for tanezumab after FDA lifted a partial hold on the pain drug.

In December 2012 FDA put restrictions on clinical studies of tanezumab, and other pain drugs that work by blocking nerve growth factor (TNF), after witnessing side effects in animal studies conducted by other companies. Later, in 2013, Pfizer signed an agreement with Lilly to jointly develop and sell tanezumab for several pain-related conditions.

Initially tanezumab showed promise as a therapy for pain in the knee and lower back, but Pfizer in 2010 suspended large late-stage trials of the drug for those conditions due to reports that patients' osteoarthritis had worsened, according to a report by Reuters. The FDA, however, later recommended that the osteoarthritis trials continue if the company enacted certain safety measures and patients did not simultaneously take other nonsteroidal anti-inflammatory drugs.

FDA Unsure if Schizophrenia Drug Caused Deaths

After a review, FDA was unable to determine whether the injectable schizophrenia drug Zyprexa Relprevv (olanzapine pamoate) caused two recent patient deaths.

In a statement the agency said: “We are unable to exclude the possibility that the deaths were caused by rapid, but delayed, entry of the drug into the bloodstream following intramuscular injection. The study suggested that much of the drug level increase could have occurred after death, a finding that could explain the extremely high blood levels found in the two patients who died 3 to 4 days after receiving injections of appropriate doses of Zyprexa Relprevv.

“On the basis of all of the information reviewed, we are not recommending any changes to the current prescribing or use of Zyprexa Relprevv injection at this time.”

Treatment with Zyprexa Relprevv may help improve the symptoms of schizophrenia, which include hearing voices, seeing things that are not there, and being suspicious or withdrawn. The labeling for Zyprexa Relprevv carries a boxed warning, FDA's most serious type of warning, for post-injection delirium sedation (PDSS). PDSS is a serious condition with signs and symptoms consistent with olanzapine overdose, in particular, sedation (including coma), delirium, or both.

Following the deaths of the two patients who received appropriate doses of Zyprexa Relprevv, FDA requested the drug's manufacturer, Eli Lilly and Company, to conduct an animal study to test whether movement of olanzapine into blood after death could lead to higher-than-expected blood levels of the drug. The study showed that some animals had increases in drug levels in the blood after death, which could account for the higher-than-expected blood levels found in the two patients who died.