ONZETRA Xsail (sumatriptan intranasal) / Otsuka, Paratek Pharmaceuticals - LARVOL DELTA

Study to Assess the Safety and Efficacy of ONZETRA® Xsail® for the Acute Treatment of Episodic Migraine With or Without Aura in Adolescents (clinicaltrials.gov) - P3 | N=159 | Terminated | Sponsor: Currax Pharmaceuticals | N=314 ➔ 159

Enrollment change • CNS Disorders • Migraine • Pain

Drugs for migraine. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • CNS Disorders • Migraine • Pain

Comparison table: Triptans. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • CNS Disorders • Migraine • Pain

Study to Assess the Safety and Efficacy of ONZETRA® Xsail® for the Acute Treatment of Episodic Migraine With or Without Aura in Adolescents (clinicaltrials.gov) - P3 | N=314 | Terminated | Sponsor: Currax Pharmaceuticals | Trial completion date: Aug 2023 ➔ Jun 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2023 ➔ Jun 2022; eDiary data collected not sufficient to utilize in the analysis of protocol endpoints

Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Migraine

Harnessing Intranasal Delivery Systems of Sumatriptan for the Treatment of Migraine. (PubMed, Biomed Res Int) - "The beneficial effects of the dry nasal powder of ST (AVP-825) have been proven in clinical studies. Based on the extant findings, harnessing novel delivery systems can improve the bioavailability of ST and enhance its effectiveness against migraine attacks. However, further clinical studies are needed to approve the safety and efficacy of employing such systems in humans."

Journal • Review • CNS Disorders • Gastrointestinal Disorder • Migraine

Study to Assess the Safety and Efficacy of ONZETRA® Xsail® for the Acute Treatment of Episodic Migraine With or Without Aura in Adolescents (clinicaltrials.gov) - P3; N=420; Recruiting; Sponsor: Currax Pharmaceuticals; Active, not recruiting ➔ Recruiting; Trial completion date: Dec 2021 ➔ Aug 2023; Trial primary completion date: Dec 2021 ➔ Aug 2023

Clinical • Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Migraine

Drugs for Migraine. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • CNS Disorders • Migraine • Pain

Lasmiditan (Reyvow) and ubrogepant (Ubrelvy) for acute treatment of migraine. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • CNS Disorders • Migraine

Evaluating Mean Level and Within-Person Consistency in Migraine Pain Intensity and Migraine-Related Disability for AVP-825 vs Oral Sumatriptan: Results from the COMPASS Study, A Randomized Trial. (PubMed, Headache) - P3 | "LSMEMs demonstrate that treatment with AVP-825 is associated with lower average migraine pain intensity and disability from 10 to 90 minutes and greater within-person consistency across multiple migraine attacks (reduced WPV) from 45 to 120 minutes post-dose compared to oral sumatriptan. These findings may reflect the more rapid and consistent absorption of sumatriptan using AVP-825. Increased WPV with AVP-825 in the first 15 minutes likely reflects the earlier onset of treatment effects with the device compared to oral sumatriptan. LSMEMs show promise as a novel approach for assessing and comparing consistency of treatment response in migraine trials."

Clinical • Journal • CNS Disorders • Migraine • Pain

Faster migraine relief using AVP-825 compared with sumatriptan tablet: Using a latent variable perspective (AHS 2016) - P3, N=259; COMPASS (NCT01667679); Sponsor: Optinose; "Results from the statistical model showed that approximately 54% of variability in general relief was between-person compared to 46% within-person. For a typical individual and attack, MR preceded DF, which preceded PF. When an individual treated an attack with AVP-825, they had significantly greater latent general relief compared to sumatriptan tablet (p < .01). In comparison with sumatriptan tablet, AVP-825 had significantly greater odds of PF (OR=3.94, p < .001), DF (OR=2.31, p < .01), and MPR (OR=1.42, p < .01)."

P3 data • Migraine

Popular migraine medicine quickly absorbed when delivered with novel breath powered OptiNose Bi-Directional nasal technology, new comparative data demonstrates (OptiNose) - OptiNose announced results of a study which deliver sumatriptan with a novel device using OptiNose breath powered Bi-Directional nasal technology; In direct comparison OptiNose’s sumatriptan sent 62% more drug into blood in critical first 15 minutes than Imitrex nasal spray (AUC 0-15=1.69 ng*hr/mL and 1.04 ng*hr/mL, respectively); OptiNose is enrolling patients in a head-to-head study comparing OptiNose nasal sumatriptan powder (16mg) to sumatriptan tablets (100mg) – the medicine in Imitrex

Clinical data • Trial initiation date • Migraine

Reduced treatment-emergent nausea using AVP-825 vs sumatriptan tablets: A comparative effectiveness study in acute migraine (AHS 2016) - P3, N=232; COMPASS (NCT01667679); Sponsor: Optinose; "The sample was 84.1% female with mean age of 40.2 years old. Participants experienced TEM within the first two hours in an average of 0.8 attacks. An individual’s propensity for TEM during an attack changed at a significantly lesser rate through the first 45 min post-dose using AVP-825 relative to oral sumatriptan (PP<.05)....AVP-825 was associated with a reduced risk of TEM compared to oral sumatriptan."

P3 data • Migraine

AVP-825 reduces migraine-associated nausea faster than sumatriptan tablets: A comparative effectiveness study (AHS 2016) - P3, N=259; COMPASS (NCT01667679); Sponsor: Optinose; "The risk for nausea varied between individuals and attacks. A typical individual’s odds for experiencing nausea during an attack decreased at a faster rate during the first hour when treating with AVP-825 compared to oral sumatriptan (PP<.05)....Findings show that AVP-825 treatment leads to more rapid reductions in nausea risk during the first hour post-treatment, and reduced odds of nausea from 30 to 120 min following treatment compared to oral sumatriptan."

P3 data • Migraine

Pharma Tech industries selected to manufacture innovative nasal delivery system for NDA submission (Businesswire) - "Pharma Tech Industries (PTI)...has been selected to handle filing, assembly and packaging services for a migraine relief medication administered through an innovative new method: a breath-powered nasal delivery system...PTI was chosen for this initiative – which will start as developmental, supporting FDA submission for approval and will continue into commercial. Pharma Tech Industries will play a critical, turn-key role in preparing OptiNose’s NDA batches over the coming months."

Anticipated FDA event • Licensing / partnership • Migraine

Avanir Pharma (AVNR) reports FDA approval of ONZETRA to Treat migraine (Streetinsider.com) - KOL: Stewart Tepper; "Avanir Pharmaceuticals...announced that the U.S. Food and Drug Administration (FDA) has approved ONZETRA™ Xsail™ (sumatriptan nasal powder), formerly known as AVP-825, for the acute treatment of migraine with or without aura in adults....'While there are many acute migraine treatment options available, more than 70% of patients are not fully satisfied with their current migraine treatment. Given this high dissatisfaction, there remains an unmet need to provide patients with fast-acting, well tolerated therapies that deliver consistent relief,' said Stewart Tepper, M.D...."

Media quote • NDA • Migraine KOL

A low incidence of atypical sensations with AVP-825 (breath powered intranasal delivery system containing 22 mg sumatriptan powder) migraine therapy across multiple phase 2/3 clinical trials (AAN 2016) - KOL: Stewart Tepper; Presentation time: April 21, 2016, 8:30 AM - 5:30 PM; Abstract #P6.106; P2, P3, N=NA; TARGET (NCT01462812); COMPASS (NCT01667679); Sponsor: Optinose; "Treatment-emergent atypical sensations occurring within 120 minutes post-dose were assessed for all attacks in COMPASS, demonstrating significantly lower rates with AVP-825 compared with oral sumatriptan (2% of 512 attacks vs 5% of 512 attacks; P=.02). In TARGET, one patient (1/112; 0.9%) on AVP-825 reported mild paresthesia that resolved spontaneously vs none with placebo. There were no reports of pressure/tightness. Of 78 patients receiving AVP-825 in the Phase 2 study, none reported any atypical sensation."

P2 data • P3 data • Migraine KOL

Avanir Pharmaceuticals' CEO hosts investor relations day (Transcript) (SeekingAlpha) - "We have three programs in Phase II clinical development...and one NDA-ready assets with AVP-825, which we expect to file the NDA in the first quarter of the calendar year 2014."

Anticipated NDA • Migraine

Characterizing the most common AEs following treatment with AVP-825: Exploring abnormal tasteand nasal discomfort across multiple attacks in COMPASS study (AHS 2016) - P3, N=217; COMPASS (NCT01667679); Sponsor: Optinose; "These findings suggest AVP-825 was well tolerated, with common AEs reported as mostly mild and transient. Most subjects treated with AVP-825 never experienced abnormal taste or nasal discomfort, regardless of the number of attacks treated in COMPASS. When present, these local AEs were usually mild and were not associated with a reduction in the number of treated attacks. Both AEs demonstrated strong within-person consistency across attacks and thus provided some indication of likelihood of experiencing abnormal taste/nasal discomfort in subsequent migraine attacks."

Adverse events • P3 data • Migraine

Reduced treatment-emergent nausea using AVP-825 vs. sumatriptan tablets: A comparative effectiveness study (AAN 2016) - P3, N=232; COMPASS (NCT01667679); Sponsor: Optinose; "Participants experienced TEM in the first two hours on an average of 0.8 attacks. An individual’s propensity for TEM during an attack changed at a significantly lesser rate through the first 45min post-dose using AVP-825 relative to oral sumatriptan (p < .05). Additionally, an individual’s odds of experiencing TEM during an attack were significantly lower using AVP-825 compared to oral sumatriptan at 45, 60, and 90min (p < .05)."

P3 data • Migraine

Primary efficacy outcomes from compass: A controlled trial comparing an intranasal delivery system containing 22 mg sumatriptan powder (AVP-825) vs 100 mg oral sumatriptan in acute treatment of migraine (PAINWeek 2015) - P3, N=275; COMPASS (NCT01667679); Sponsor: Optinose US Inc.; "Significantly greater reduction in migraine pain intensity over the first 30 minutes post-dose was observed with AVP-825 vs oral-SUM (SPID-30: 10.80 vs 7.41 P<.001). At all time points from 15-90 minutes postdose, significantly greater rates of pain relief and pain freedom were achieved with AVP-825 vs oral-SUM (e.g., at 30 minutes: 53.8% vs 38.7% P<.0001 and 18.2% vs 10.8% P=.0003, respectively)....Treatment was well tolerated, with a statistically significantly lower rate of atypical sensations with AVP-825 vs oral-SUM (2% vs 5% of attacks, P=.02)."

P3 data • Migraine

Faster migraine pain and disability relief using AVP-825 compared to sumatriptan tablet: Applying a novel method for evaluating migraine relief across multiple outcomes (AmPS 2016) - P3, N=259; COMPASS (NCT01667679); Sponsor: Optinose US; "Results showed that an individual treated with AVP-825 had a higher likelihood of achieving Very Rapid relief compared to sumatriptan tablet (p <.01). Findings showed that the MEPSUM model can be used to parsimoniously describe time-to multiple migraine-related relief outcomes simultaneously. AVP-825 treatment predicted greater odds of “Very Rapid” patterns of migraine relief, characterized by the fastest time-to pain freedom, disability freedom and meaningful pain relief, compared to sumatriptan tablets."

P3 data • Migraine

A low incidence of atypical sensations with AVP-825 (breath powered intranasal delivery system containing 22 mg sumatriptan powder) migraine therapy across multiple phase 2/3 clinical trials (AHS 2016) - P2/3, N=NA; TARGET (NCT01462812); Sponsor: Optinose; COMPASS (NCT01667679); Sponsor: Optinose; "In COMPASS, treatment-emergent atypical sensations occurring within 120 minutes post-dose were reported at significantly lower rates with AVP-825 vs oral sumatriptan (2% of 512 attacks vs 5% of 512 attacks; P50.02). In TARGET, one patient (1/112; 0.9%) on AVP-825 reported mild paresthesia that resolved spontaneously vs none with placebo. There were no reports of pressure/tightness. Of 78 patients receiving AVP-825 in the Phase 2 study, none reported atypical sensations; one subject receiving placebo experienced oral paresthesia."

P2/3 data • Migraine

Rapid response in migraine patients treated with breath powered intranasal delivery of sumatriptan powder (AVP-825): Efficacy analysis by prior triptan history from the phase 3 TARGET study (AAN 2016) - P3, N=165; TARGET (NCT01462812); Sponsor: Optinose; "Patients previously using ≥2 triptans had significantly greater pain relief rates with AVP-825 (n=34) vs placebo (n=40) from 30 minutes (47.1% vs 23.1%, P<.05) through 120 minutes (61.8% vs 35.0%, P<.05). AVP-825 conferred superior pain freedom rates from 45 minutes (23.5% vs 5.1%, P<.05) through 120 minutes (32.4% vs 7.5%, P<.01). Pain relief rates in AVP-825 patients who had previously used ≥2 triptans were generally consistent with those for ≤1 triptan. In patients previously using sumatriptan, AVP-825 (n=49) was superior to placebo (n=42) for rates of pain relief from 30 minutes (51.0% vs 22.0%, P<.01) through 120 minutes (77.6% vs 38.1%, P<.001), and pain freedom from 45 minutes (22.5% vs 4.9%, P<.05) through 120 minutes (36.7% vs 4.8%, P<.001)."

P3 data • Migraine

Avanir Pharmaceuticals announces submission of New Drug Application for AVP-825 for the acute treatment of migraine (Avanir Pharmaceuticals Press Releases) - "The company's 505(b)(2) NDA for AVP-825 includes data from one pivotal phase III clinical trial for the acute treatment of migraine. The NDA is also supported by data from a phase II placebo-controlled clinical trial for acute treatment of migraine, and two pharmacokinetic studies. Overall, the submission includes safety data from 222 subjects...and references data from the extensive clinical use of sumatriptan over the past 20 years."

NDA • Migraine

COMPASS study: Benefits of AVP-825 vs oral sumatriptan on treating migraine pain (ANA 2015) - Abstract #M409; P3, N=259; COMPASS (NCT01667679); Sponsor: Optinose US Inc.; "AVP-825 treated attacks showed significantly faster rates of pain reduction at 10, 15, 30 minutes (p<.05) compared to attacks treated with sumatriptan tablets. Pain was consistently lower throughout the first 60 minutes post-treatment with AVP-825 versus treatment with oral sumatriptan. AVP-825 reduced migraine pain severity more rapidly within the first 30 minutes compared to 100 mg sumatriptan, and had lower overall migraine pain severity during the first hour of treatment."

P3 data • Migraine