dm+d

Unassigned

New Medicines

Vydura (EU), Nurtec (US) Migraine prevention

Information

Vydura (EU), Nurtec (US)
New molecular entity
Biohaven Pharmaceuticals
Biohaven Pharmaceuticals

Development and Regulatory status

None
Pre-registration (Filed)
Launched
May 21Approved in US for preventive treatment of adult patients with episodic migraine, e.g. those who experience ≤15 headache days per month. Product label includes use of up to 18 doses/month, allowing for both acute and preventive therapy in the same patient [9].
Mar 21Filed in EU via centralised procedure for acute treatment and prevention of migraine [8].
Nov 20Biohaven reports that scientific advice for rimegepant for acute and prophylaxis migraine treatment was received from the EMA CHMP in June and December 2018, respectively. Based on this feedback, it believes it has several potential pathways to approval, which it is pursuing. Biohaven plans to file in Europe in Q1 21 [6].
Oct 20US FDA accept sNDA for rimegepant for preventative treatment of migraine, with a PDUFA date of Q2 21 [5].
May 20Biohaven plans to file an sNDA for rimegepant for prevention of migraine later in 2020; plans for EU filing not described [4].
Mar 20Biohaven intends to file pivotal PIII data in the US & EU [3].

Category

Calcitonin gene-related peptide (CGRP) receptor antagonist, orally-active small molecule. Taken every other day.
Numbers may be misleading, as many who experience migraine do not consult their GP, but migraine affects about 6% of men and 18% of women. In children it is more common in boys than in girls. The first attack is often in childhood and over 80% have had their first attack by the age of 30 [2].
Migraine prevention
Oral

Further information

Yes

Trial or other data

Dec 20PII/III RCT (NCT03732638; n=747) reports rimegepant was superior to placebo for change in mean number of migraine days per month during weeks 9–12 (−4.3 days vs. −3.5, respectively; mean difference −0.8, 95% CI −1.46 to −0.20; p=0.0099 [7].
Mar 20 Biohaven Pharmaceuticals announces that a PII/III trial met its primary endpoint of reduction in mean number of migraine days in patients with migraine (NCT03732638; BHV3000-305). Those receiving rimegepant 75 mg every other day (n=348) experienced a statistically significant 4.5 day reduction from baseline in monthly migraine days, compared to a 3.7 day reduction in the placebo group (n=347; p=0.0176). Among study participants not taking concomitant preventive treatment, there was a 4.9 day reduction in monthly migraine days in the rimegepant group (n=273) compared with a 3.7 day reduction in the placebo group (n=269; nominal p=0.0020). A total of 22% of the study participants were taking a concurrent preventive treatment, including topiramate and amitriptyline. 48% of the rimegepant group had at least a 50% reduction from baseline in the mean number of moderate to severe migraine days per month compared to 41% in the placebo group [3].
Nov 18 PII/III trial evaluating the safety and efficacy of rimegepant in preventing migraine starts (NCT03732638; BHV3000-305). 1,200 adults will be recruited in the US. Primary outcome is change from baseline in mean number of migraine days per month in the last four weeks; collection of these data is due to complete Dec 19 [1].

Vydura (EU), Nurtec (US) Acute migraine

Information

Vydura (EU), Nurtec (US)
New molecular entity
Biohaven Pharmaceuticals
Biohaven Pharmaceuticals

Development and Regulatory status

None
Pre-registration (Filed)
Launched
Mar 21Filed in EU via centralised procedure for acute treatment and prevention of migraine [21].
Nov 20Biohaven reports that scientific advice for rimegepant for acute and prophylaxis migraine treatment was received from the EMA CHMP in June and December 2018, respectively. Based on this feedback, it believes it has several potential pathways to approval, which it is pursuing. Biohaven plans to file in Europe in Q1 21 [20].
Mar 20In it latest annual report, Biohaven does not describe specific plans to file for approval of rimegepant for acute treatment in the EU. However, in a press release they announce positive results from a pivotal PIII trial for preventative treatment of migraine and state that they intend to file these data in the US & EU [19].
Mar 20Nurtec orally disintegrating 75mg tablet launched in the US for acute treatment of migraine in adults [18].
Feb 20Approved in the US [17].
Feb 20Analysts predict this will be one of the top 10 most-anticipated new US drug launches of 2020 based on estimated global sales in 2024 [14].
Nov 19The NDA was submitted on the basis of results from the PIII BHV-3000-301, BHV3000-302 and BHV3000-303 trials [13].
Nov 19FDA assigns PDUFA action date of Q1 20 for orally dissolving tablet formulation of rimegepant. Biohaven plans US launch Q1 20 [13].
Jul 19Has been filed in the US [13].
May 19Biohaven announces in its quarterly report that in Feb 18, a request for scientific advice for rimegepant was submitted to the Committee for Medicinal Products for Human Use and feedback was received in Jun 18. Based on this feedback, they believe there are several potential pathways to approval [10].
Mar 19Biohaven has successfully conducted a pre-NDA submission meeting with the US FDA & secured a US FDA priority review voucher (PRV), which it will submit alongside its NDA for rimegepant for the treatment of migraine, Q2 19. The basis of NDA submission will be the PIII BHV-3000-301, BHV3000-302 and BHV3000-303 trials [9].
Jun 18Biohaven enters into an exclusive worldwide license agreement with Catalent UK Swindon Zydis Limited (a subsidiary of Catalent Inc), to provide Zydis® ODT (orally disintegrating tablet) fast-dissolving formulation technology, for developing rimegepant and other small molecule CGRP receptor antagonists [9].
May 18Biohaven has an exclusive, worldwide license agreement with Bristol-Myers Squibb for all development and commercialisation rights to rimegepant [7].
Mar 18Biohaven expects to file with the US FDA in 2019.[6]
Jul 17Two pivotal PIII trials initiated in the US (NCT03235479, NCT03237845), with expected primary completion dates early in 2018 [1].

Category

Calcitonin gene-related peptide (CGRP) receptor antagonist, orally-active small molecule
Numbers may be misleading, as many who experience migraine do not consult their GP, but migraine affects about 6% of men and 18% of women. In children it is more common in boys than in girls. The first attack is often in childhood and over 80% have had their first attack by the age of 30 [2].
Acute migraine
Oral

Trial or other data

Jul 19Results of PIII NCT03461757 are published; RCT (n=1466) reported that at 2 h postdose, rimegepant, an investigational calcitonin gene-related peptide receptor antagonist, was superior to placebo for freedom from pain (21% vs 11%, p<0.0001) and freedom from the most bothersome symptom (35% vs 27%, p=0.0009) [12].
Jul 19Results of NCT03237845 RCT (n=1186) are pulished; the study found rimegepant resulted in higher percentage of patients who were free of pain (19.6 vs. 12.0%; p<0.001) and free from most bothersome symptom (37.6 vs. 25.2% p<0.001) than placebo 2 hours after receiving dose. Most common adverse events were nausea and UTI [11].
Dec 18Pooled safety data released by Biohaven Pharmaceuticals for BHV-3000-301 (NCT03235479), BHV3000-302 (NCT03237845) and BHV3000-303 (NCT03461757) trials [9].
Oct 18Biohaven completes a PIII trial and evaluate the efficacy and safety of orally disintegrating tablet (ODT) formulation of rimegepant (the fast-dissolve Zydis®) in the treatment of acute migraine (BHV3000-303; NCT03461757). The randomised, double-Blind, placebo controlled trial was initiated in February 2018 and enrolled 1,466 patients in the US [9].
Mar 18Positive top-line results from two PIII trials (NCT03235479, NCT03237845) of rimegepant for migraine. In both trials, rimegepant met the co-primary efficacy endpoints of superiority to placebo at 2 hours after dosing in pain freedom and freedom from most bothersome symptoms such as nausea or sensitivity to light or sound. The rate of pain freedom in the 2 trials was 19.2% and 19.6% vs. 14.2% and 12% for placebo. Freedom from most bothersome symptoms was 37.6% and 36.6% v.s 25.2% and 27.7% in the placebo arm.[6]
Feb 18Biohaven initiates a third PIII efficacy study of rimegepant, for the treatment of migraine. The study is expected to complete in Q4 18 [9].
Nov 17Biohaven announces completion of enrollment in PIII study BHV3000-302 (NCT03237845). Together with PIII study BHV3000-301 (NCT03235479), the trials enrolled approximately 3,000 pts with migraine. Topline results are expected in Q1 of 2018. Long-term safety data will be evaluated in a third trial, Study BHV3000-201.[4,5]
Jul 17Two pivotal PIII randomised placebo-controlled trials initiated (NCT03235479, NCT03237845), both recruiting solely in the US. Both have the same design, with estimated recruitment of 850 patients each, and twin primary outcomes: freedom from pain at two hours, and freedom from the most bothersome symptom of nausea, phonophobia or photophobia, vs. placebo. Estimated completion for both trials is early February 2018 [3].

Evidence based evaluations