Zecuity (transdermal sumatriptan) / Teva - LARVOL DELTA

Phase 1 Dose Escalation and Dose Expansion Trial of NP-101 in Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=35 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2024 ➔ Mar 2025

Enrollment open • Trial initiation date • Oncology • Solid Tumor

First report on QSAR modelling for chemical penetration enhancement ratio (ER) of different FDA-approved drugs in Poloxamer 407: A next step towards better skin permeability of drugs. (PubMed, Int J Pharm) - "Additionally, an ex vivo study was performed on selected drugs (Voriconazole, Terbinafine, Ketoconazole, Pantoprazole, Sumatriptan, Sitagliptin, and Rabeprazole) to evaluate the predictive power of the developed 2D-QSAR model...This QSAR-based prediction study highlights the potential for forecasting the skin penetration abilities of various drug classes in the presence of Poloxamer 407. It also provides a foundation for designing pharmaceutical dosage forms with improved skin permeability, which could aid in the treatment of skin-related conditions and other diseases."

FDA event • Journal

NP-101 in Combination with Nivolumab and Ipilimumab in Metastatic Extra-pulmonary Neuroendocrine Carcinomas (EP-NECs): A Pilot Study (NANETS 2024) - P1 | "CONCLUSIONS The combination of NP-101 plus dual ICPIs (nivolumab and ipilimumab) was safe and well-tolerated with preliminary evidence of anti-neoplastic activity. A randomized phase II clinical trial studying the combination is now under development."

Clinical • Combination therapy • Metastases • Dermatology • Endocrine Cancer • Fatigue • Gastrointestinal Disorder • Immunology • Neuroendocrine Tumor • Oncology • Pain • Pruritus • Rheumatology • Solid Tumor

Phase 1 Dose Escalation and Dose Expansion Trial of NP-101 in Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=35 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P1 trial • Oncology • Solid Tumor

Individual ingredients of NP-101 (Thymoquinone formula) inhibit SARS-CoV-2 pseudovirus infection. (PubMed, Front Pharmacol) - "We demonstrated that NP-101, TQ, and other individual ingredients, including oleic, linoleic, and palmitic acids inhibited SARS-CoV-2 infection in the MLV-based pseudovirus model. A large, randomized phase 2 study of NP-101 is planned in outpatient COVID-19 patients."

Journal • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Respiratory Diseases

BOSS-002: Study of the Safety, Tolerability and Efficacy of NP-101 in Treating High Risk Participants Who Are Covid-19 Positive. (clinicaltrials.gov) - P2a/2b | N=308 | Recruiting | Sponsor: Novatek Pharmaceuticals | Trial completion date: Aug 2023 ➔ Dec 2023 | Trial primary completion date: Jun 2023 ➔ Oct 2023

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Evaluation of Gum Arabic Double-layer Microneedle Patch Containing Sumatriptan for Loading and Transdermal Delivery. (PubMed, Curr Drug Deliv) - "The release amount of drug from 12 patches made of the prepared microneedles was comparable to that of subcutaneous injection, providing a new possibility for migraine treatment."

Journal • CNS Disorders • Migraine • Pain

Autism spectrum disorder in architecture perspective: a review of the literature and bibliometric assessment of research indexed in Web of Science. (PubMed, F1000Res) - "The study identified a massive gap in the development of literature in ASD for architecture design and built environment perspective, the most important and trending keywords are missing, and the analyses also showed a lack of subject development. The authors have suggested areas and keywords for further research to fulfill the gap in the future."

Journal • Review • Autism Spectrum Disorder • Genetic Disorders

Characterization of a Novel AAV Gene Replacement Therapy, VY-NPC101, In Vitro and In Vivo for the Treatment of Niemann-Pick Disease Type C1 (ASGCT 2022) - "These results led to the identification of VY-NPC101. In summary, the rational design of VY-NPC101, and validation in a NPC1 disease-relevant cells lines and an NPC1 mouse model support its continued development and translation into the clinic."

Preclinical • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Bioisosteric discovery of NPA101.3, a second generation RET/VEGFR2 inhibitor optimized for single-agent polypharmacology. (PubMed, J Med Chem) - "Oral administration of NPA101.3 (10 mg/kg/day) completely prevented formation of tumours induced by RET/C634Y-transformed cells, while it decreased, but did not abrogate, formation of tumours induced by a control oncogene (HRAS/G12V). The balanced synchronous inhibition of both RET and VEGFR2, as well the resistance to demethylation, renders NPA101.3 a potential clinical candidate for RET-driven cancers."

Journal • Oncology

Transdermal Delivery of Sumatriptan Succinate Using Iontophoresis and Dissolving Microneedles. (PubMed, J Pharm Sci) - "Tests, carried out with Franz diffusion cells and skin of Göttingen minipigs, showed that small decreases in the polymer concentration led to negligible lag times and marked increases in the cumulative amount of drug permeated in 6 hours (Q) and in the flux (J). At 500 μA/cm, Q and J nearly doubled for a microneedle loaded with 5% (w/w) sumatriptan and 20% (w/w) PVP (Lag Time = 0 min; Q = 2888 μg/cm; J = 490 μg/cm/h) relative to a system loaded with 5% (w/w) drug and 30% (w/w) PVP (Lag Time = 36 min; Q = 1437 μg/cm; J = 266 μg/cm/h)."

Journal

Experimental and Mathematical Study of the Transdermal Delivery of Sumatriptan Succinate from Polyvinylpyrrolidone-based Microneedles. (PubMed, Eur J Pharm Biopharm) - "The calculated diffusion coefficients were one order of magnitude greater than the value estimated when the drug was directly applied to the skin surface. The dissolution rate constant was affected by the concentration of the polymer matrix."

Journal

Teva Branded Pharmaceutical Products R&D, Inc.; Withdrawal of Approval of a New Drug Application for ZECUITY (Sumatriptan Iontophoretic Transdermal System) (Federal Register) - "The Food and Drug Administration (FDA) is withdrawing the approval of the new drug application (NDA) for ZECUITY (sumatriptan iontophoretic transdermal system) held by Teva Branded Pharmaceutical Products R&D, Inc....Teva requested withdrawal of this application and has waived its opportunity for a hearing....Approval is withdrawn as of July 2, 2020."

NDA • CNS Disorders • Migraine • Pain

Permeation of sumatriptan succinate across human skin using multiple types of self-dissolving microneedle arrays fabricated from sodium hyaluronate. (PubMed, J Drug Target) - "These findings suggest that high-density MNs of 800 μm in length are an effective and promising formulation for transdermal delivery of SS. To our knowledge, this is the first report of SS permeation across human skin using self-dissolving MNs."

Journal • Biosimilar • Ophthalmology

2017 will be a breakthrough year for migraine, says AMF Chair - KOL: David Dodick; "At this year’s American Headache Society conference, Dr. David Dodick presented the initial plans for a major new 2017 Migraine Awareness Campaign that the AMF is betting will break through in a big way. It’s focus: 'to education and inform, and then build empathy and action.'"

Media quote • Migraine KOL

Teva announces U.S. availability of Zecuity (sumatriptan iontophoretic transdermal system), first and only transdermal patch system for the acute treatment of migraine (Teva Press Release) - "Teva Pharmaceutical...announced that ZECUITY®, the first and only patch system designed to provide relief from migraine, is now available by prescription through specialty pharmacies. ZECUITY® is a single-use, disposable patch system that delivers sumatriptan through the skin."

Launch US • Migraine

Nupathe: Corporate Presentation (NuPathe) - Anticipated patent expiry in US for transdermal methods and systems for the delivery of anti-migraine compounds in Apr 2027; Anticipated patent expiry in US for polyamine formulation in Apr 2029; Anticipated patent expiry in US for pharmacokinetics of iontophoretic sumatriptan administration in Apr 2027; Anticipated patent expiry in US for self-contained, wearable iontophoretic devices in Feb 2023; Anticipated patent expiry for electronic controls and safety in 2032; Anticipated patent expiry for co-packaging system for iontophoretic delivery system in 2032; Anticipated patent expiry for pad detection system in 2032; Anticipated patent expiry for methods of iontophoretically treating nausea & migraine in 2032

Anticipated patent expiry • Migraine

NuPathe: Corporate Presentation (NuPathe) - "Pain relief and nausea freedom two-hours following patch activation; Twice as many patients treated with Zecuity achieve freedom from headache pain compared to placebo; 53% of patients treated with Zecuity achieved relief from headache pain compared with 29% for placebo; 84% of patients treated with Zecuity were nausea-free compared with 63% for placebo"

P3 data • Migraine

Nupathe: Q4 and FY 2012 Results (NuPathe) - Anticipated product exclusivity for migraine through April 21, 2029

Anticipated commercial • Migraine

Modulation of inducible pain signaling molecules in a model of traumatic brain injury (AHS 2015) - Abstract #OR18; "MK8825 and sumatriptan significantly reduced the level of iNOS mRNA and iNOS immunoreactiviy in the TNC and ganglia, p 0.01. Sumatriptan significantly reduced CGRP levels in the TNC, p  <  0.01. iNOS deletion significantly attenuated CGRP at 3 days post-injury, when there was an exaggerated increase in CGRP levels compared to 2 week groups, p  <  0.05. iNOS deletion in mice did not significantly reduce CGRP levels at 2 weeks post-injury."

Preclinical • Migraine

Endo to acquire specialty pharmaceutical company NuPathe (NuPathe Press Release) - "Endo Health Solutions...entered into a definitive agreement under which Endo will acquire NuPathe Inc. (Nasdaq: PATH) for $2.85 per share in cash, or approximately $105 million. In addition to the upfront cash payment, NuPathe shareholders will receive rights to receive additional cash payments of up to $3.15 per share if specified net sales of NuPathe’s migraine treatment ZECUITY are achieved over time...we plan to launch ZECUITY in the first half of 2014...The transaction is expected to be completed in early 2014.” 

M&A • Migraine

NuPathe terminates agreement with Endo and enters into agreement to be acquired by Teva (NuPathe Press Release) - "NuPathe...has terminated its agreement and plan of merger with Endo Health Solutions...also entered into an agreement and plan of merger with Teva...In addition to the upfront cash payment, NuPathe stockholders will receive rights to receive additional cash payments of up to $3.15 per share if specified net sales of NuPathe's migraine treatment, ZECUITY®, are achieved over time....The transaction is expected to be completed in February 2014 "

M&A • Migraine

NuPathe to present Zecuity data at the 2013 International Headache Congress (NuPathe Press Release) - P3, N=530; PREDICT (NCT00724815); Sponsor: NuPathe; P=NA N=48; NuPathe...will present data on Zecuity...Patients who had migraine-related nausea (MRN) at the time of treatment were nearly twice as likely to report their headache pain as "severe" than those without MRN at the time of treatment (31% vs. 16%)...All of the migraine patients and healthcare professionals safely and successfully assembled, applied and activated Zecuity."

Anticipated P3 data • Migraine

Teva: Business Outlook Conference Call (Teva) - Anticipated launch in US in Q2 2015

Anticipated launch US • Migraine

NuPathe's Zecuity approved by the FDA for the acute treatment of migraine (NuPathe) - "NuPathe announced FDA...approved Zecuity (sumatriptan iontophoretic transdermal system) for the acute treatment of migraine with or without aura in adults. Zecuity was approved based upon...P3 trials that included 800 patients using more than 10,000 Zecuity patches. In P3 pivotal study...twice as many patients treated with Zecuity achieved freedom from headache pain at two hours compared with PBO(18% and 9%, respectively). 53% of patients treated with Zecuity...relief from headache pain and 84% were nausea free at two hours (29% and 63%, respectively, with PBO). Launch of Zecuity expected in the Q4 of this year."

Anticipated launch US • FDA event • Migraine