Trudhesa (dihydroergotamine mesylate intranasal) / Impel Pharma - LARVOL DELTA

Cardiovascular safety of dihydroergotamine mesylate delivered by precision olfactory delivery (INP104) for the acute treatment of migraine. (PubMed, Headache) - "In two separate studies, INP104 demonstrated a favorable CV safety profile when used in a study population without CV-related contraindications."

Journal • Cardiovascular • CNS Disorders • Migraine • Pain

Prediction of Pharmacokinetics of Repeat Dosing of Dihydroergotamine Mesylate Via Precision Olfactory Delivery (INP104) (AAN 2024) - "Repeat-dose PK was predicted using the Phoenix WinNonlin nonparametric superposition tool. Based on the approved US prescribing information, the following schedules were simulated for 1.45 mg INP104: two doses 1 hour apart, one dose daily for 3 days, one dose every 2 days for 5 days.Conclusions Simulations of repeat dosing of INP104 indicate that giving two doses 1 hour apart will produce higher exposures compared with a single dose, but there is limited accumulation with any other repeat dosing regimen."

PK/PD data • CNS Disorders • Migraine • Pain

Real-world assessment of concomitant migraine medication use in patients using INP104 (Trudhesa®) in the United States (PAINWeek 2023) - "During baseline, 49.7% of patients used a migraine preventive medication (32.2% gepants; 24.5% anticonvulsants; 18.4% beta-blockers; 15% CGRP mAbs; 11.7% topiramate; 11.5% SSRIs). Real-world evidence in patients with migraine suggests a treatment gap remains with approximately half of patients not receiving appropriate preventive medication. Most patients were not using DHE prior to INP104 use. Following INP104 use, concomitant preventive (with the exception of the CGRP mAb class) and acute medication use generally decreased between the 12-month baseline and 90-day follow-up period, which suggests that INP104 may be an effective acute therapy for managing migraine."

Clinical • Real-world • Real-world evidence • CNS Disorders • Migraine • Pain

Assessment of the Potential for Drug–Drug Interactions Between INP104 (Trudhesa®) and Gepants for Migraine Management Using a Model-based Approach (PAINWeek 2023) - " This was a critical evaluation for potential pharmacokinetic or pharmacodynamic DDIs between INP104 and atogepant, rimegepant, or ubrogepant. Based on available data, no DDIs of clinical concern are predicted when recommended clinical doses of INP104 and gepants are coadministered."

CNS Disorders • Migraine • Pain

"Spherix Global Insights would like to congratulate @pfizer on the launch of Zavzpret™ (zavegepant) for the acute treatment of migraine. Zavzpret is the first and only anti-CGRP nasal spray. #migraine #pfizer #zavzpret #ubrelvy #reyvow #nurtec #trudhesa" (@SpherixNeuro)

Clinical • CNS Disorders • Migraine • Pain

Zavegepant (Zavzpret) for acute treatment of migraine. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • CNS Disorders • Migraine • Pain

Safety of INP104 in Migraine Patients With Cardiovascular Risk Factors: Post Hoc Subgroup Analysis of the Phase 3 STOP 301 Study (AHS 2023) - "This is a post hoc subgroup analysis of all patients from STOP 301 with known non-significant CV risk factors. Overall, the most frequently occurring TEAEs with INP104 use were not cardiac related in migraine patients with non-significant CV risk factors. Further studies in patients with known stable CV risk factors in the absence of CV contraindications for DHE may be warranted."

Clinical • P3 data • Retrospective data • CNS Disorders • Migraine • Pain

Safety of Concomitant Triptan and INP104 Use From the Phase 3 STOP 301 Study in Migraine Patients (AHS 2023) - "DHE and triptans act on 5-HT1B/1D receptor subtypes, which contributes to their vasoconstrictive effects; therefore, administering 5-HT1 agonists (eg, sumatriptan) within 24 hours of DHE use is contraindicated. Although in a small population, the safety of concomitant triptan and INP104 use was reported, which is an important topic for the patient/physician dialogue."

Clinical • P3 data • CNS Disorders • Migraine • Pain

Real-World Assessment of Baseline Demographic and Clinical Characteristics Among Patients Using INP104 in the United States (AHS 2023) - "Real-world evidence demonstrates that most patients with migraine treated with INP104 are female, are between the ages of 36 and 45 years, and have comorbidities that include headache syndromes other than migraine, other neurologic conditions, other pain disorders, sleep disorders, GI disorders, and psychiatric disorders. Unlike in other epidemiological studies, in this real-world patient population, GI comorbidities were more common than those in the psychiatric category."

Clinical • Real-world • Real-world evidence • Back Pain • Bipolar Disorder • CNS Disorders • Depression • Epilepsy • Mental Retardation • Migraine • Mood Disorders • Musculoskeletal Pain • Pain • Post-traumatic Stress Disorder • Psychiatry • Sleep Disorder • Substance Abuse

Assessment of the Potential for Drug–Drug Interactions Between INP104 and Gepants for Migraine Management Using a Model-based Approach (AHS 2023) - " This was a critical evaluation for potential pharmacokinetic or pharmacodynamic DDIs between INP104 and atogepant, rimegepant, or ubrogepant. Based on available data, no DDIs of clinical concern are predicted when recommended clinical doses of INP104 and gepants are coadministered."

CNS Disorders • Migraine • Pain

Real-World Assessment of Concomitant Medication Use in Patients Using INP104 in the United States (AHS 2023) - "Of those patients who used a preventive medication during the 12-month baseline period, 32.2% used a gepant (rimegepant or atogepant), 24.5% used an anticonvulsant, 18.4% used a beta-blocker, 15.0% used an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody, 11.7% used topiramate, and 11.5% used a selective serotonin reuptake inhibitor (SSRI; <10% in each category)...During the 90-day follow-up period with INP104 use, 23.3% used a gepant (ubrogepant or rimegepant), 15.4% used an NSAID, 9.9% used a triptan, 8.1% used an opioid, 3.1% used a barbiturate, 2.6% used a ditan, 0.4% used acetaminophen, and 0% used domperidone as acute medications for migraine... Real-world evidence in patients with migraine suggests a treatment gap may remain, with approximately half of patients not receiving appropriate preventive medication; however, the frequency and severity of migraine need to be considered to determine who is a good candidate for preventive therapy. Most..."

Clinical • Real-world • Real-world evidence • CNS Disorders • Migraine • Pain

INP104: a drug evaluation of a nonoral product for the acute treatment of migraine. (PubMed, Pain Manag) - "Here, we provide a drug evaluation of INP104, a novel drug-device combination product of dihydroergotamine (DHE) mesylate - a molecule with a long history of efficacy familiar to headache specialists - which is delivered to the difficult-to-reach upper nasal space where it is rapidly and consistently absorbed via Precision Olfactory Delivery (POD). In clinical trials, INP104 exhibited favorable pharmacokinetics, a well-tolerated safety profile, and rapid symptom relief, highlighting its potential as a suitable acute therapy for migraine."

Journal • Review • CNS Disorders • Gastrointestinal Disorder • Migraine • Pain

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

Journal • CNS Disorders • Migraine • Pain

Impel Pharmaceuticals to Present New Real-World Data for Trudhesa at the 65th Annual Scientific Meeting of the American Headache Society (GlobeNewswire) - "Impel Pharmaceuticals...today announced it will present new real-world data adding to the growing body of evidence supporting Trudhesa....The findings will be featured in two poster presentations during the 65th Annual Scientific Meeting of the American Headache Society (AHS), taking place June 15-18, 2023, in Austin, Texas....Preliminary real-world findings from an assessment of medical and pharmacy claims data for patients with migraine who were treated with Trudhesa in the United States provide new evidence suggesting that concomitant preventive...and acute medication use generally decreases in patients taking Trudhesa between the 12-month baseline and 90-day follow-up period....A second poster on real-world demographic and clinical characteristics, as well as baseline comorbidities among patients with migraine who were treated with Trudhesa, found that most patients were females between the ages of 36 and 45 years, and had comorbidities..."

Clinical data • Real-world • Retrospective data • CNS Disorders • Migraine • Pain

Impel Pharmaceuticals Announces First Quarter 2023 Financial Results and Provides Business Update (GlobeNewswire) - "To-date, Trudhesa continues a strong trajectory with more than 87,000 prescriptions generated since launch. Based on third-party data, it is estimated that at the end of April 2023, Trudhesa accounted for 4.7 percent of branded acute migraine prescriptions (nTRx) among prescribers. We continue to see the benefits from increasing the sales force in July of 2022. New Trudhesa patients increased by 18 percent from Q4 2022 to Q1 2023, driven by an expanded, more efficient and increasingly productive sales force. Reimbursement of all shipments was 72 percent in Q1 2023, compared with 60 percent in Q4 2022....The Company’s net revenue from sales of Trudhesa was $4.4 million for Q1 2023. This compared to net revenues of $1.8 million for Q1 2022. The increase is due to growth in Trudhesa sales volume and improvements in net price realization."

Commercial • Reimbursement • Sales • CNS Disorders • Migraine • Pain

Impel Pharmaceuticals Presents New Data at AAN 2023 Suggesting Trudhesa Nasal Spray is Safe to Use When Co-Administered With Commonly Prescribed Migraine Medications (GlobeNewswire) - "Impel Pharmaceuticals...presented results from the first-ever pharmacokinetic (PK) and pharmacodynamic (PD) evaluation of potential drug-drug interactions (DDIs) between Trudhesa^® (dihydroergotamine [DHE] mesylate) nasal spray (0.725 mg per spray) and orally administered gepant medications....The study authors believe that the PD profiles of DHE and gepants are not anticipated to overlap significantly given their differing mechanisms of action, though potential PD DDIs cannot be completely excluded. Additionally, while first-pass metabolism may limit the bioavailability of orally administered drugs, since Trudhesa is administered via the upper nasal space, it bypasses the gastrointestinal (GI) and hepatic first-pass metabolism."

PK/PD data • CNS Disorders • Migraine • Pain

Impel Pharmaceuticals Presents New Data at AAN 2023 Suggesting Trudhesa Nasal Spray is Safe to Use When Co-Administered With Commonly Prescribed Migraine Medications (GlobeNewswire) - P3 | N=360 | STOP 301 (NCT03557333) | Sponsor: Impel Pharmaceuticals | "Impel Pharmaceuticals...presented results from the first-ever pharmacokinetic (PK) and pharmacodynamic (PD) evaluation of potential drug-drug interactions (DDIs) between Trudhesa^® (dihydroergotamine [DHE] mesylate) nasal spray (0.725 mg per spray) and orally administered gepant medications....An additional analysis from the pivotal, Phase 3 STOP 301 trial found that concomitant use of Trudhesa and erenumab, a preventive CGRP-based therapy, is well tolerated with the majority of adverse events being mild or moderate and considered unrelated to treatment. Meanwhile, another analysis in a small population found that no significant safety concerns emerged consequent to off-protocol concomitant use of triptans and Trudhesa during the STOP 301 trial."

P3 data • CNS Disorders • Migraine • Pain

Impel Pharmaceuticals to Present Data on Trudhesa Nasal Spray for Treatment of Acute Migraine at 2023 American Academy of Neurology Annual Meeting (GlobeNewswire) - "Impel Pharmaceuticals...announced today that four Trudhesa® (dihydroergotamine mesylate) nasal spray (0.725 mg per spray) abstracts have been selected to be presented at the upcoming American Academy of Neurology (AAN) Annual Meeting taking place in Boston, MA, April 22-27, 2023."

Clinical data • P3 data • CNS Disorders • Migraine • Pain

Assessment of the Potential for Drug–Drug Interactions Between INP104 and Gepants for Migraine Management Using a Model-based Approach (AAN 2023) - "Design/Methods This was a critical evaluation for potential pharmacokinetic or pharmacodynamic DDIs between INP104 and atogepant, rimegepant, or ubrogepant. No clinically relevant DDIs from inhibition of, or being a substrate for, transporter proteins by gepants or DHE are anticipated because of limited data, but cannot be excluded. Conclusions Based on available data, no DDIs of clinical concern are predicted when recommended clinical doses of INP104 and gepants are coadministered."

CNS Disorders • Gastrointestinal Disorder • Migraine

Safety of Concomitant Triptan and INP104 Use From the Phase 3 STOP 301 Study in Migraine Patients (AAN 2023) - "DHE and triptans act on 5-HT1B/1D receptor subtypes, which contributes to their vasoconstrictive effects; therefore, administering 5-HT1 agonists (eg, sumatriptan) within 24 hours of DHE use is contraindicated. No TEAEs related to blood pressure, pulse, or electrocardiogram parameters were reported, and any variance was within normal clinical limits. Conclusions Although in a small population, the safety of concomitant triptan/INP104 use was reported, which is an important topic for the patient/physician dialogue."

Clinical • P3 data • CNS Disorders • Migraine

Safety and Efficacy of Concomitant Erenumab and INP104 Use From the Phase 3 STOP 301 Study in Migraine Patients (AAN 2023) - "At months 1, 2, 3, 4, 5, and 6, 32.3% and 54.3%, 37.1% and 70.8%, 33.3% and 50.0%, 40.3% and 68.1%, 28.0% and 42.7%, and 26.7% and 33.3% self-reported 2-hour pain and MBS freedom post-INP104, respectively. Conclusions Results suggest that INP104 may be an effective and well-tolerated acute therapy for migraine patients who concomitantly use erenumab as a preventive therapy, with sustained benefits over 6 months."

Clinical • P3 data • Cardiovascular • CNS Disorders • Migraine • Pain • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

A Cross-Sectional Survey of Prevailing Opinions from Headache Specialists Regarding Status Migrainosus Management (AAN 2023) - "Although no evidence-based treatment guidelines for SM exist, treatment can include steroids, nerve blocks, nonsteroidal anti-inflammatory drugs, triptans, ergotamine, neuroleptics, and dihydroergotamine mesylate (DHE)...Conclusions Headache specialists treat multiple SM patients per week and value treatments that break the headache and offer sustained pain relief while avoiding ER visits. Although DHE was viewed favorably for SM, it was underutilized and often only as a last resort due to accessibility issues."

CNS Disorders • Migraine • Pain

Impel Pharmaceuticals Announces Fourth Quarter and Full Year 2022 Financial Results and Provides Business Update (GlobeNewswire) - "Impel Pharmaceuticals Inc...reported financial results for the fourth quarter and full year ended December 31, 2022 and provided a business update....To-date, Trudhesa continues a strong trajectory with more than 58,400 prescriptions generated in 2022. Based on third-party data, it is estimated that at the end of December Trudhesa accounted for 4.3 percent of branded acute migraine prescriptions (nTRx) among prescribers....The Company’s net revenue from sales of Trudhesa was $5.0 million and $12.7 million for the fourth quarter and full year 2022, respectively. This compared to net revenues of $0.6 million and $0.7 million for the fourth quarter and full year 2021, respectively."

Commercial • Sales • CNS Disorders • Migraine • Pain

Impel Pharmaceuticals Announces Strategic Reprioritization, Continues Focus on Maximizing Trudhesa Commercial Opportunity (BioSpace) - "Trudhesa Growth Momentum Continues, with 58 Percent Increase in New Prescriptions from Q2 2022 to Q4 2022 Following Expansion of Sales Force...Impel Pharmaceuticals...today announced that it will implement an operational streamlining plan that will include a reduction of employee and non-employee expenses, largely impacting the research and development functions of the organization. The Company plans to reprioritize spend to capitalize on the continued positive momentum in payor and prescriber uptake of Trudhesa® (dihydroergotamine mesylate) nasal spray (0.725 mg per spray)....Along with increased focus on the commercialization of Trudhesa, Impel will continue with its evaluation of strategic and financing initiatives and opportunities to fully leverage the therapeutic potential of its proprietary POD technology and expertise with both small and large molecules in multiple disease areas."

Commercial • CNS Disorders • Migraine • Pain

"$IMPL Impel Pharmaceuticals Announces Strategic Repriortization, Continues Focus on Maximizing Trudhesa® Commercial Opportunity https://t.co/Tfb6LMNUrY" (@stock_titan)