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AMERICAN SOCIETY OF CLINICAL PSYCHOPHARMACOLOGY (ASCP)
June 2014
Hollywood, FL
by Lynne Peterson
June 16-18, 2014
The annual meeting of the American Society of Clinical Pharmacology (ASCP) is a forum for issues in clinical research in psychiatry. It used to be known as the NCDEU (New The ASCP meeting offered a peek at Clinical Drug Evaluation Unit) meeting and was sponsored by the National Institute of both the good and the bad news in Mental Health (NIMH). Now, it is run by ASCP but with the partnership of NIMH, the psychopharmacology drug National Institute on Drug Abuse (NIDA), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the FDA. Researchers are struggling with trial design issues, especially assay sensitivity A lot of big pharmas have pretty much exited the psychopharmacology development area. and the increasing rate of placebo There is still a lot of work being done in multiple sclerosis and Alzheimer's disease, but response, and a slowdown in big pain, schizophrenia, and depression have quieted down. pharma interest in pain, schizophrenia, Daniel Burch, MD, vice president and therapeutic area head for neuroscience at Pharma- Promising drugs include: ceutical Product Development (PPD), a contract research organization (CRO), said,  Alcobra's metadoxine ER for
"Neurology is busier than it ever has been…but psychiatry is in a little bit of a lull…Big pharma will jump back into depression and schizophrenia if cognition targets work out."  Alkermes' ALKS-5461 for depres-
sion and aripiprazole lauroxil for A key issue in the field right now is the lack of assay sensitivity, which he said was a big topic of discussion at the ASCP meeting – and which is good for his business, "If you have  Cerecor's CERC-301 for depres-
a dramatically impactful drug, then you can show an effect on a small sample size, but these diseases are complex and pretty intractable…The challenge now is finding the right targets and making sure you have the right assay…A lot of this meeting is about trial Intra-Cellular Therapies' ITI-007
for schizophrenia and more.
Johnson & Johnson's Ketanest, a
Dr. Burch said another hot topic right now is the placebo response in clinical trials, "There nasal ketamine for depression. is some natural force going on that we don't understand…Placebo response in depression  Pherin Pharmaceuticals'
trials has been going up, up, and up. Why? There are lots of reasons it might be going up, aloradine for anxiety. but no one knows for sure…And as placebo goes up from 20% to 30% to 40%, it is much more difficult to show separation from the active drug…What can be done about it? Are we getting the patients in the trials? At the end of the day, a lot of this is very sub-jective. There are even websites where people can learn to be depressed subjects to get in trials. That is particularly a problem in southern California, New York, and Florida." Stephen Snyder, Publisher 2731 N.E. Pinecrest Lakes Blvd. Among the other points about specific disorders that Dr. Burch made were: Jensen Beach, FL 34957 "For Alzheimer's I don't think we will come up with something dramatic; probably it
Fax 772-334-0856 will be a cocktail that slows the disease or improves symptoms or a combination of both…We will see what happens with the BACE inhibitors and beta-amyloid, but there are other things being investigated for symptoms." Trends-in-Medicine has no financial connections with any pharmaceutical or medical device company. The information and opinions expressed have been compiled or
arrived at from sources believed to be reliable and in good faith, but no liability is assumed for information contained in this newsletter. Copyright 2014.
This document may not be reproduced without written permission of the publisher.


June 2014/ASCP Page 2

 "Autism drugs have been disappointing [so far]."
granted orphan drug status by the FDA in December 2013 as a potential pro-cognitive agent in Fragile X syndrome, a genetic "Degenerative diseases are tough. We don't understand
disorder that causes intellectual disability, behavioral and all we need to know about the biology. We need a lot of learning challenges, and various physical characteristics, but it basic research and translational stuff to say will it turn into also is being investigated in ADHD and other cognitive dis- something meaningful in the lab."  "In depression, the jury is not quite out on NMDA antag-
onists and ketamine drugs…Depression is still an area of Dr. Rubin described it as rapidly effective with no potential for high unmet need. The problem there is assay sensitivity… abuse or addiction in animal models. The mechanism of action The only drugs approved for depression work through the is not yet fully understood, but he said it is monoamine- monoamine pathway (serotonin, dopamine)…If the independent, a GABA/glutamate modulator, and a serotonin Alkermes drug [ALKS-5461] is successful, this will be the 5-HT2B receptor antagonist. first approval not in that pathway, so it is pioneering in that perspective…The trial design is unusual but it may be a Completed Phase II trials include: good way to help with assay sensitivity…And I would watch  A 120-patient, 6-week Phase IIb study in Israeli adults with the Intra-Cellular Therapies drug [ITI-007]…The NMDAs ADHD. The primary endpoint was CAARS-INV, which work in people who failed other therapies and will be rapid Dr. Rubin said is an accepted endpoint by the FDA for registration studies, and the drug showed a "moderate"  "In multiple sclerosis, neuroprotection is the next fron-
effect (0.4 point effect size), which started at Week 2 and tier. Anti-CD20s will be really good advances, and they continued out to Week 6. In a subgroup of predominantly have to top that. They have to find ways to get nerves inattentive ADHD patients, there was a bigger effect (0.9). He said, "That is considered a strong effect size…We see a preferential effect on the predominantly inattentive subtype,  "In pain, we still have the opiates, the COX-1 and -2
and we believe that merits further exploration." In terms of inhibitors, and Neurontin [Pfizer, gabapentin], but not much safety, there were no serious adverse events, some nausea else. It is kind of like Alzheimer's disease – a pretty tough and initial insomnia, but no effect on appetite or mood. nut to crack. The key may be to go after syndromes…The 5-HTP inhibitors – on top of acetylcholinesterase inhibitors  A 36-patient, crossover, single-dose Phase IIb study in – for symptomatic Alzheimer's are interesting." Companies ADHD. The high dose (1400 mg) significantly improved to watch in this space: Lundbeck, Otsuka, and GlaxoSmith- the TOVA ADHD score (p=0.009), but the low dose was not significant.  "Schizophrenia is in a little lull right now. There is a lot
A 300-patient Phase III trial in ADHD is underway in the U.S. of cognition work being done. The nicotinic receptor antag- and Israel with the 1400 mg dose, and a pediatric ADHD study onists are very important there…Will they be dramatic? is expected to start soon. A Phase IIb study in Fragile X Probably not. You will probably need 200-500 patients to adolescents and adults is about to start, with a pivotal Fragile X show a difference." study planned for 2015. INTRA-CELLULAR THERAPIES' ITI-007
– a serotonin 5-HT
2A receptor antagonist for schizo-
phrenia, bipolar disorder, and other neuropsychiatric
A session on drugs in the psychopharmacology pipeline indications
highlighted some possible winners – and a few failures. Kimberly Vanover, PhD, vice president of clinical develop- ment at Intra-Cellular, said that a 335-patient, placebo- ALCOBRA PHARMA's metadoxine extended-release
controlled Phase II trial in acute schizophrenia met the primary – a synthetic antioxidant for ADHD and cognitive
endpoint (PANSS score change) with the low dose (60 mg QD) disorders
but not with a higher dose (120 mg QD), adding, "We can't Jonathan Rubin, MD, MBA, chief medical officer of Alcobra, fully explain that." But she said the company is taking the 60 an Israeli specialty pharma, said that the immediate-release mg dose forward into Phase III. formulation of this drug has been approved in some countries since the 1980s to treat alcohol intoxication and alcoholic liver Dr. Vanover said, "Unlike risperidone, it improved negative disease. Alcobra's proprietary dual-release formulation was symptoms, especially in patients with negative symptoms at


June 2014/ASCP Page 3
baseline…There was significant improvement in certain RS-IV, which Dr. Wilens described as "a very positive, very PANSS subscales consistent with improved social function, and dramatic response – from 40 to 17…The efficacy is reminis- significant improvement in other prosocial measures, such as cent of lisdexamfetamine [Shire's Vyvanse], a very significant reduced depression…There were also anecdotal reports of reduction. They also showed improvement across the board more social interaction – patients coming out of their rooms… on scales of executive function at Week 4, a signal that We did a post hoc analysis, and the 60 mg dose had a statis- executive function improves as well as ADHD symptoms." tically significant improvement in the prosocial PANSS factor There was no immediate relapse with discontinuation. A Phase score, with an effect size of 0.6, which is encouraging." IIb trial is planned. In terms of safety, she said the drug was safe and well toler- ated, with no cardiovascular issues, adding, "Unlike risperi- PHERIN PHARMACEUTICALS' aloradine (PH-94B)
done it does not cause sustained tachycardia…Numerically, – a synthetic neuroactive intranasal steroid for acute
there is less weight gain than risperidone. And there was no symptoms of anxiety
increase in suicidal ideation or behavior." Michael Liebowitz, MD, founder and former director of the Anxiety Disorders Clinic at the New York State Psychiatric A Phase III trial in acute schizophrenia is in the planning stage. Institute and a member of Pherin's scientific advisory board, said an early study showed decreased heart and respiratory rates, increased alpha EEG and body temperature, with some JOHNSON & JOHNSON's Ketanest (esketamine)
subjects spontaneously reporting feeling distinctly calmer and – an NMDA receptor antagonist in treatment-
resistant depression
Several companies have tried to develop a ketamine for A randomized, double-blind, 91-patient, longitudinal Phase II treatment-resistant depression (TRD), including BioLineRx, trial in social anxiety disorder found that symptoms were Cypress Bioscience, and Johnson & Johnson. So far, nothing reduced in 75.6% of aloradine patients vs. 37% of placebo has been really successful, though experts continue to believe patients. Both performance anxiety symptoms and social inter- the drug has utility, with quick onset. The drug is generally action anxiety were reduced during a public speaking safe but has CNS symptoms in 50% of patients. challenge, and the effect was quick (within 15 minutes). After an end-of-Phase II meeting with the FDA, the company is J&J's version is an intranasal spray formulation that is still in revising its Phase III protocol and expects to start Phase III clinical trials. trials this year. The key issue is whether the FDA and/or the Drug Enforcement Dr. Liebowitz also said a study is just getting going where Administration (DEA) would ever approve any formulation of a drug patients rate themselves in real-life situations. known to illegal drug users as "Special K" because of the abuse potential. NEUROVANCE's centanafadine (EB-1020)
– non-stimulant for adult attention-deficit/hyper-
The pipeline session also included a few failures. activity disorder (ADHD)
Timothy Wilens, MD, a pediatric psychopharmacologist from ASTRAZENECA
Massachusetts General Hospital, said this drug has "strong  AZD-8529 – an mGluR2 modulator for schizo-
biological plausability," and in preclinical studies it looked phrenia. Alan Cross, PhD, senior director of neuroscience
"almost identical to placebo and very different from amphet- at AstraZeneca, said a Phase IIa trial found no significant amine" in terms of abuse liability. Human abuse liability improvement in cognitive performance or reduction in studies are underway. Dr. Wilens said studies show the clinical symptoms vs. either placebo or Johnson & Johnson's standard-release formulation has no food effect and no Risperdal (risperidone). Dr. Cross said, "Whether a differ- insomnia but a small, dose-related increase in heart rate ent treatment regimen and adjunct treatment would provide consistent with what is seen with norepinephrine. a benefit remains to be determined…We have done a lot of ad hoc analyses, and nothing stands out…Ad hoc analyses Top-line results from a 4-week pilot study in 40 adult males have failed to identify a subgroup of responders." with ADHD showed a statistically significant change in ADHD-


June 2014/ASCP Page 4

Lanicemine (AZD-6765) – an NMDA channel
VOYAGER PHARMACEUTICALS' leuprolide acetate
blocker for depression. Two posters reported on the
– an anti-androgen for Alzheimer's disease
results of the Phase IIb PURSUIT study, in which two doses Richard Bowen, MD, a primary care physician with OTB (50 mg and 100 mg IV) failed to beat placebo in major Research in Charleston SC and a co-founder of Voyager, depressive disorder (MDD). In fact, the Kaplan-Meier reported on the 48-week, double-blind, 109-patient curves were nearly identical on the MADRS score. Post hoc ALADDIN study of women given leuprolide (AbbVie's analyses suggested the explanation could be high placebo Lupron) for Alzheimer's disease (AD), and this anti-androgen response, less stringent criteria for treatment resistance, therapy failed on both primary and all secondary endpoints. lower baseline severity of depression, the level of study center experience, and more. It is not clear whether However, Dr. Bowen said there is anecdotal evidence AstraZeneca is abandoning this drug, but the company suggesting a synergistic effect with acetylcholinesterase inhib- reportedly has a "family" of compounds in the cupboard. itors, and an a priori analysis of the trial data did show a statistically significant effect on ADAS-COG and CGIC, par- ticularly a slowing in decline in both. The study was sponsored JOHNSON & JOHNSON/JANSSEN and ADDEX PHARMA-
by Voyager Pharmaceuticals, not AbbVie. CEUTICALS' JNJ-40411813/ADX-71149
– an mGluR2 PAM modulator for major depressive
disorder
Justine Kent, MD, a psychiatrist with Janssen, said a 121- patient, multicenter, placebo-controlled Phase II trial in MDD with anxiety symptoms missed the primary endpoint (HDRS ALKERMES' ALKS-5461 [buprenorphine + samidor-
score), but it did show efficacy in some other measures, phan (ALKS-33)]
– a partial mu agonist (buprenorphine) + a mu
17, HAM-D6, and IDS-30. antagonist (samidorphan)
In the second part of the study, where patients who did not Alkermes believes this combination will provide efficacy with respond to placebo were re-randomized to drug or placebo, less or no euphoria or abuse potential. In a Phase II study the there was a clear separation between drug and placebo, combination was superior to placebo in improving depressive suggesting that a sequential parallel comparison design (SPCD) symptoms. There were several posters on this combination trial design might show positive response. To confuse things even more, the high dose performed worse in the first phase of  A rat study looked at the method of action. the study but better in the second phase. In terms of adverse events, there was significant dizziness (34%) and vertigo (23%) A dose-finding, multicenter, double-blind, placebo-con- – as has been seen with other mGluRs. Dr. Kent said the trolled Phase II trial study, using an SPCD design, found that dizziness is probably a class effect. a 1:1 ratio (2 mg of each drug) was the best combination. An Alkermes official said the company plans to explore Dr. Kent concluded, "While an efficacy signal is evident, the doses lower than 2 mg/2 mg. totality of the data suggest a lack of a strong drug effect."
SPCD is a new trial design developed by Maurizio Fava, MD,
and David Schoenfeld, MD, of Massachusetts General Hospital. It utilizes two stages of treatment – first stage where the
TARGACEPT's TC-5619
investigative drug is compared to placebo, and a second phase – an alpha7 neuronal nicotinic receptor (NNR) agon-
that only studies placebo non-responders, who are re-random- ist in schizophrenia
ized to either drug or placebo. Alkermes reportedly has said David Hosford, MD, PhD, vice president of clinical the FDA has agreed to accept an SPCD structured trial for development and regulatory affairs at Targacept, described a registration, and Alkermes officials at ASCP said that SPCD "registration-quality," 185-patient, 24-week Phase IIb trial will be used in the Phase III trial of ALKS-5461, but they conducted in the U.S. and India – that failed to show a benefit would not say whether the FDA is requiring other analyses as on the primary endpoint – a composite SANS score at both well, but one official said, "It is a complex design." doses tested (5 mg and 50 mg) – or any of the secondary This design is aimed at eliminating placebo response, so the true drug effect can be seen. The problem will be that in Dr. Hosford said the one small good news was a positive effect clinical practice there is no way to identify the placebo in smokers, but he said that was probably a false positive. responders. In an oncology trial, it is likely the FDA would


June 2014/ASCP Page 5
require a companion diagnostic, but there is no equivalent diagnostic in psychopharmacology. What do experts think about the SPCD design, the FDA approvability of a drug using the design, and the implications for clinical use of a First-generation vs. second-generation LAIs. At a
drug approved using the design? session on LAIs, Taishiro Kishimoto, MD, PhD, a psychiatrist from Keio University School of Medicine, reported on a meta-  "It lowers the expectation of the clinician and the patient. It analysis of 21 randomized clinical trials with a total of 5,130 is probably a passing thing." patients, comparing LAIs to oral antipsychotics. Surprisingly,  William Potter, MD, PhD, a senior advisor at the National the LAIs were no better than the oral drugs. When just Institute of Mental Health: "Because the treatment is so safe, double-blind, double-dummy studies were examined, there any way we can enrich the patient population and show an was still no difference between LAIs and orals. And when effect is okay, but it doesn't tell you how to select patients trials of the same active ingredient were compared, again there in the real world. The FDA will accept SPCD [for registra- was no difference between LAIs and orals. However, when first-generation LAIs were compared to  "SPCD could be a negative by getting you to continue devel- second-generation LAIs, there was a difference. First- opment of a drug that will fail." generation LAIs were significantly superior to oral agents, but  "It's far from real life…The Achilles heel with SPCD is the second-generation LAIs were not. When older studies were same as with crossover studies – the person in the second compared to newer studies, LAIs beat orals only in the older arm is not the same person." studies, not in the newer studies.  "It's a good design. It solves the problem of the increasing So, how did Dr. Kishimoto explain these counter-intuitive findings? placebo response." He said it could be due to differences in relapse definitions, selection bias, or even publication bias (negative studies may A researcher for another company said he had heard that not have been published in the past). ALKS-5461 will have to be a DEA-scheduled drug. Week 4 Results in Phase II Trial of ALKS-5461
Second-generation oral antipsychotics vs. LAIs. Nina
Measurement
ALKS-5461
Schooler, PhD, a psychiatrist from Zucker Hillside Hospital, described the 305-patient, 30-month PROACTIVE study HAM-D17 change in all comparing second-generation oral antipsychotics with LAIs, which found orals numerically superior but not statistically HAM-D17 change in placebo non-responders different from LAIs on the primary endpoint of time to relapse. MADRS change in all Time to first hospitalization also favored orals, but not signifi- cantly. On psychosis symptoms, the LAIs did a little better placebo non-responders Asked how there can be a difference in psychosis symptoms that doesn't CERECOR's CERC-301
translate into a difference in relapses, Dr. Schooler said, "At the – an NMDA inhibitor
beginning 20% of patients are psychosis symptom-free when they enter the trial…That bounces around for orals…but with A poster was presented on the Phase II trial design for this oral patients on LAIs it increases to almost 40% of patients…This is agent (which is specific to NR2B), using a variation of SPCD. an interesting finding. I would have expected patients who The focus with this agent is on the rapidity of the effect. It were psychosis-free to do better on a scale of functioning, and was "repurposed" from Merck (MK-0657) which had tested it we didn't see an improvement in that." unsuccessfully in Parkinson's disease. Data are expected by the end of 2014. The company has not yet found a partner to take CERC-301 into Phase III. Paliperidone vs. haloperidol. Joseph McEvoy, MD, a
psychiatrist from Duke University, reported on the result of There is a chance this might not be a DEA-scheduled drug. An the ACLAIMS trial comparing monthly paliperidone (Johnson investigator said, "It has a half-life of 14 hours, so lacks the & Johnson's Invega Sustenna) and haloperidol. There was no classic signal of abuse drugs." But he admitted addiction difference between the two drugs on the primary endpoint of studies will need to be done.


June 2014/ASCP Page 6
rate of failure (relapse) within 8 weeks (33.8% vs. 32.4%). In ALKERMES' aripiprazole lauroxil
fact, the Kaplan-Meier curves were virtually identical. – a promising atypical antipsychotic
Alkermes developed the long-acting technology for J&J's And there was weight gain with paliperidone vs. weight loss Risperdal Consta and Invega Sustenna. Now, the company is with haloperidol (+2.17 kg vs. -0.96 kg). There was no developing its own long-acting antipsychotic, aripiprazole difference between the two drugs in tardive dyskinesia or lauroxil, a prodrug of Otsuka and Lundbeck's Abilify Maintena Parkinson measures, but there was more Barnes akathisia with (monthly aripiprazole). The results of a multicenter, double-blind, 12-week, 623- Paliperidone vs. risperidone. A J&J poster reported on a
patient Phase III trial of aripiprazole lauroxil vs. placebo in retrospective claims database analysis which found that patients acute schizophrenia were presented in a poster at ASCP. Two switching from Johnson & Johnson's Risperdal Consta (risperi- doses were tested – 441 mg (comparable to 300 mg Abilify done monthly) to Invega Sustenna had a lower risk of Maintena) and 882 mg (equivalent to 600 mg Abilify Maintena) schizophrenia-related relapse and a longer duration of therapy – and both met the primary endpoint, significantly reducing than patients switching from Risperdal Consta to an oral the PANSS score (a measure of positive and negative symptoms) vs. placebo (-21, -22, and -10 points, respectively). The results for the two doses were nearly superimposable. As with Abilify Maintena, the efficacy was apparent early (by Day 8) and continued to improve throughout the entire 12 weeks. ABBVIE's ABT-126 – a selective alpha7 nicotinic acetyl-
The adverse events also were similar to what has been seen choline receptor agonist that failed
with Abilify Maintena and oral daily Abilify (aripiprazole). In A Phase II study presented in a poster at ASCP tested 2 doses particular, the akathisia rate was 11.3%, which Otsuka vs. placebo. Neither dose showed a significant improvement in researchers said is comparable to their drug. An Alkermes MCCB composite score, but there was a definite trend. In the researcher said, "We don't expect a different adverse event pre-specified subgroup of non-smokers, there was a significant label from aripiprazole since we had 600 patients in our 38% improvement in MCCB score with both doses, but no study, and 25,000 patients have been studied with aripip- improvement in smokers. The researchers concluded that it is worth studying ABT-126 further. The poster was presented by Srdjan (Serge) Stankovic, MD, Two Phase IIb studies are ongoing and nearly completed with MSPH, senior vice president of clinical development and medi- higher doses – a 430-patient study in smokers and a 150- cal affairs at Alkermes. He said, "We are very happy with the patient study in non-smokers. It should be kept in mind that effect size with both doses. Another exciting thing is there is 60% of schizophrenics are smokers. such consistency in the effect; the primary endpoint and all the secondary endpoints were met, with the effect starting early and continuing throughout the study…We believe the onset of ALKERMES' samidorphan (ALKS-33) + olanzapine
action is quite impressive…On tolerability, we didn't see any- – a promising mu antagonist + an atypical anti-
thing not expected with oral aripiprazole…What I like is the psychotic
consistency. This is about flexibility." A Phase II study has started combining samidorphan + olanzapine in schizophrenia. A company researcher said they Dr. Stankovic said Alkermes plans to file aripiprazole lauroxil think the samidorphan will attenuate the weight gain with with the FDA in 3Q14 for the treatment of acute schizo- olanzapine without reducing its antipsychotic efficacy. Another Phase II trial is expected to start this summer of this Asked how their drug differs from Abilify Maintena, Alkermes combination in schizophrenic patients with an alcohol problem. researchers cited several things that differentiate aripiprazole  Flexibility in dosing. Dr. Stankovic said, "Once it is
injected, the dissolution is slow…It is a smooth dissolution." Approval will be sought for at least two doses, which will


June 2014/ASCP Page 7
allow doctors to use either dose – or anything in between  "The side effect profile looks impressive. I see more off-label. Abilify Maintena only comes in one approved akathisia with oral aripiprazole. There is no real advantage dose. Another Alkermes official said, "In our filing, we will over the existing Abilify Maintena except for the higher provide dosing recommendations, not necessarily starting all dose, but it is another option. It's all a marketing play." patients at 441 mg."  "Whether I use it will depend on the side effects."  Convenience. It will come in a pre-filled syringe for
easier administration. This is a real advantage since Abilify  "The only difference is the delivery technology." Maintena requires mixing.  "It is nice data, but it is the same drug. It is another option.  Administration. The low dose (but not the high dose)
The deltoid injection is an advantage." can be injected into the deltoid (arm); Abilify Maintena  "The higher dose of Abilify was worse than the lower dose must be injected in the buttocks. However, Otsuka also is [on the pivotal trial], but the FDA still approved it, so I think working on a deltoid version of Abilify Maintena and the FDA will approve both of these doses." expects to submit that to the FDA in September 2014. Onset. The onset of action is quick. As with other long-
"It has two doses, comes in a pre-filled syringe, and there is acting antipsychotics, this drug is expected to have a more give at the end of the month if someone misses a dose. requirement for an oral antipsychotic for three weeks after Having that window would be nice – but when someone has the first injection. Dr. Stankovic said the acute data have been on a long-acting antipsychotic for a long time, it is not never been published on Abilify Maintena, but an Otsuka a disaster if they don't take the next dose exactly 30 days researcher said that Abilify Maintena separates from placebo during the first week, and Otsuka has filed for an expanded  "Abilify Maintena is the only long-acting antipsychotic that I label for treatment of acute schizophrenia, and that is use because of the lower rate of prolactinemia…If this were currently under review by the FDA. available, I might use it as a first option in 20% of my patients during the first year. It would be especially good Alkermes is studying whether the duration of aripiprazole for erratic patients who have a pattern of missing shots. And lauroxil can be extended beyond 30 days (e.g., 45 days). the pre-filled syringe means less work for my nurses and my There is a hint that the drug lasts longer than 30 days, and that might give doctors and patients a little wiggle room with when the next dose has to be administered. Alkermes officials said the company also is working on other durations of action (possibly a Q3M dose), but Lundbeck is working on a Q3M formulation of Abilify Maintena, and Johnson & Johnson has a Q3M formulation of Invega Sustenna under review by the FDA now. Is there a need for another long-acting injectable (LAI) antipsychotic? Dr. Stankovic said, "This is not about competing with other LAIs but about getting practices to get more comfortable with LAIs and increase their use. Right now, fewer than 10% of schizophrenics are on an LAI." Psychiatrists who viewed the data on aripiprazole lauroxil generally described it as a me-too but were receptive to another option, depending on price and insurance coverage. There was little excitement about it, but doctors were receptive to the idea, and they did like some of the features. Many said use will depend on marketing. Among the comments were:  "Patients did very well on it."

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