zavegepant oral (BHV-3500 oral) / Pfizer - LARVOL DELTA

A Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention (clinicaltrials.gov) - P2/3 | N=1753 | Terminated | Sponsor: Pfizer | N=538 ➔ 1753

Enrollment change • CNS Disorders • Migraine • Pain

Deconvoluting zavegepant drug-drug interactions: A phase I study to evaluate the effects of rifampin and itraconazole on zavegepant pharmacokinetics. (PubMed, Clin Transl Sci) - "This Phase I, open-label, fixed-sequence study evaluated the effects of itraconazole (a strong cytochrome P450 3A4 [CYP3A4] and P-glycoprotein [P-gp] inhibitor) on the pharmacokinetics of intranasal/oral zavegepant and the effects of rifampin (a strong inducer of CYP3A4 and P-gp; and an inhibitor of organic anion transporting polypeptide 1B3 [OATP1B3]) on oral zavegepant in healthy participants. These results suggest that OATP1B3 and intestinal P-gp are the more prominent pathways, as opposed to CYP3A4, for a zavegepant drug-drug interaction. Coadministration of OATP1B3 inhibitors with zavegepant nasal spray should be avoided."

Journal • P1 data • PK/PD data • CNS Disorders • Migraine • Pain • CYP3A4

Population pharmacokinetic modeling of zavegepant, a calcitonin gene-related peptide receptor antagonist, in healthy adults and patients with migraine. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Age (range 18-71 years), race, ethnicity, sex, renal function, and co-administration of oral contraceptives or sumatriptan did not significantly change zavegepant pharmacokinetics. Moderate hepatic impairment (Child-Pugh score 7-9) or co-administration of rifampin decreased elimination clearance of oral zavegepant by ~40%. The zavegepant population pharmacokinetic model adequately characterized zavegepant concentration-time profiles, the bioavailability of intranasal and oral zavegepant, as well as the effect of intrinsic and extrinsic factors on zavegepant pharmacokinetics."

Journal • PK/PD data • CNS Disorders • Hepatology • Migraine • Pain

Intranasal zavegepant for the acute treatment of migraine. (PubMed, Expert Rev Neurother) - "Dysgeusia was common; future studies are needed to better characterize this adverse event. Head-to-head studies are lacking with other migraine-specific therapies; the decision to treat should be patient-centered, with attack-specific characteristics in mind."

Clinical • Journal • Review • Cardiovascular • CNS Disorders • Migraine • Pain

Safety and Efficacy Active Drug vs. Placebo in Subjects With Asthma (clinicaltrials.gov) - P1 | N=45 | Terminated | Sponsor: Pfizer | Phase classification: P1b ➔ P1 | N=15 ➔ 45

Enrollment change • Phase classification • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Evidence for lack of drug-drug interaction between intranasal zavegepant and oral CGRP inhibitors for treatment of migraine based on literature analysis (AHS 2024) - "Clinically relevant DDIs between intranasal zavegepant and oral CGRP inhibitors rimegepant, atogepant and ubrogepant are not expected."

CNS Disorders • Migraine • Pain • CYP3A4

A Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention (clinicaltrials.gov) - P2/3 | N=542 | Terminated | Sponsor: Pfizer | Active, not recruiting ➔ Terminated; Strategic decision to discontinue the study based on adjusted clinical development plan. This decision is not based on any safety concerns.

Trial termination • CNS Disorders • Migraine • Pain

Physiologically-based Pharmacokinetic Modeling for Assessment of the Drug-drug Interaction Potential of Zavegepant (AAN 2024) - "Observed oral and intranasal zavegepant DDI with itraconazole (strong CYP3A4 and P-gp inhibitor) and observed oral zavegepant DDI with multiple-dose (MD) rifampin (strong CYP3A inducer; OATP1B3 and NTCP inhibitor) were used to estimate the contribution of P-gp (intestine and liver) and hepatic uptake transporters, respectively, and incorporated into the model. Models predicted DDI of intranasal zavegepant with single-dose (SD) or MD rifampin, cyclosporine A (OATP1B3, NTCP, and P-gp inhibitor), and moderate (efavirenz) or strong (carbamazepine) CYP3A4 and/or P-gp inducers...PBPK modeling and observed clinical pharmacokinetic data support zavegepant labeling recommendations that CYP3A4 inhibitors/inducers or P-gp inhibitors do not have clinically relevant effects on zavegepant exposure. OATP1B3/NTCP inhibitors may significantly increase zavegepant exposure and co-administration should be avoided."

PK/PD data • CNS Disorders • Migraine • Pain

A Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention (clinicaltrials.gov) - P2/3 | N=538 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=1440 ➔ 538

Enrollment change • Enrollment closed • CNS Disorders • Migraine • Pain

A Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention (clinicaltrials.gov) - P2/3 | N=1440 | Recruiting | Sponsor: Pfizer | Active, not recruiting ➔ Recruiting | N=435 ➔ 1440

Enrollment change • Enrollment open • CNS Disorders • Migraine • Pain

A Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention (clinicaltrials.gov) - P2/3 | N=435 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=1440 ➔ 435 | Trial completion date: Dec 2028 ➔ Mar 2024 | Trial primary completion date: Dec 2027 ➔ Mar 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Migraine • Pain

A Study to Learn About the Study Medication, Zavegepant, in Healthy Volunteers (clinicaltrials.gov) - P1 | N=52 | Completed | Sponsor: Pfizer

New P1 trial

A Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention (clinicaltrials.gov) - P2/3 | N=1440 | Recruiting | Sponsor: Pfizer | Trial completion date: Dec 2027 ➔ Dec 2028

Trial completion date • CNS Disorders • Migraine • Pain

Safety and Efficacy Active Drug vs. Placebo in Subjects With Asthma (clinicaltrials.gov) - P1b | N=15 | Terminated | Sponsor: Pfizer | Completed ➔ Terminated; Strategic decision to discontinue the study based on adjusted clinical development plan. This decision is not based on any safety concerns.

Trial termination • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Phase 1 Study to Evaluate the Effects of Rifampin on the Pharmacokinetics of Oral Zavegepant (AHS 2023) - "Co-administration of rifampin and zavegepant was hypothesized to potentially decrease zavegepant exposure due to induction of CYP3A4 and/or P-gp. The data from the study suggest that multiple mechanisms are in play. The approximately 2-fold increase in exposure suggests that zavegepant is a substrate of uptake transporters, which are inhibited by rifampin."

P1 data • PK/PD data • CNS Disorders • Migraine • Pain • CYP3A4

Safety and Efficacy Active Drug vs. Placebo in Subjects With Asthma (clinicaltrials.gov) - P1b | N=15 | Completed | Sponsor: Pfizer | Recruiting ➔ Completed | N=24 ➔ 15

Enrollment change • Trial completion • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Effects of the Strong CYP3A4 and P-glycoprotein Inhibitor Itraconazole on the Pharmacokinetics of Oral and Intranasal Zavegepant (AAN 2023) - "Increased exposure following oral zavegepant with itraconazole is likely due to itraconazole inhibition of gastrointestinal P-gp. Overall, all treatments were well tolerated and exhibited a favorable safety profile."

PK/PD data • CNS Disorders • Gastrointestinal Disorder • Migraine • CYP3A4

A Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention (clinicaltrials.gov) - P2/3 | N=1440 | Recruiting | Sponsor: Pfizer | N=2900 ➔ 1440 | Trial completion date: Jul 2023 ➔ Dec 2027 | Trial primary completion date: Jul 2023 ➔ Dec 2027

Enrollment change • Trial completion date • Trial primary completion date • CNS Disorders • Migraine

Safety and Efficacy Active Drug vs. Placebo in Subjects With Asthma (clinicaltrials.gov) - P1b | N=24 | Recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | Trial completion date: Nov 2022 ➔ Mar 2023 | Trial primary completion date: Oct 2022 ➔ Feb 2023

Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Pfizer Completes Acquisition of Biohaven Pharmaceuticals (Businesswire) - "Pfizer Inc...announced today the completion of its acquisition of Biohaven Pharmaceutical Holding Company Ltd., the maker of NURTEC® ODT (rimegepant), an innovative migraine therapy approved for both acute treatment and prevention of episodic migraine in adults....Pfizer acquired all of the outstanding shares of Biohaven not already owned by Pfizer for $148.50 per share in cash, for a total transaction consideration of approximately $11.6 billion. As a result of the acquisition, Biohaven became a wholly-owned subsidiary of Pfizer. Effective immediately prior to the closing of the acquisition, Biohaven completed the spin-off of Biohaven Ltd. (NYSE: BHVN), distributing Biohaven Ltd.’s shares to Biohaven’s shareholders."

M&A • CNS Disorders • Migraine • Pain

Safety and Efficacy Active Drug vs. Placebo in Subjects With Asthma (clinicaltrials.gov) - P1b | N=24 | Recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | Trial completion date: Jun 2022 ➔ Nov 2022 | Trial primary completion date: Jun 2022 ➔ Oct 2022

Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention (clinicaltrials.gov) - P2/3 | N=2900 | Recruiting | Sponsor: Biohaven Pharmaceutical Holding Company Ltd. | Trial completion date: Sep 2022 ➔ Jul 2023 | Trial primary completion date: Sep 2022 ➔ Jul 2023

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

Safety and Efficacy Active Drug vs. Placebo in Subjects With Asthma (clinicaltrials.gov) - P1b; N=24; Recruiting; Sponsor: Biohaven Pharmaceuticals, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Safety and Efficacy Active Drug vs. Placebo in Subjects With Asthma (clinicaltrials.gov) - P1b; N=24; Not yet recruiting; Sponsor: Biohaven Pharmaceuticals, Inc.

New P1 trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate the Efficacy and Safety of Oral Zavegepant in Migraine Prevention (clinicaltrials.gov) - P2/3; N=2900; Recruiting; Sponsor: Biohaven Pharmaceutical Holding Company Ltd.; Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Migraine