Ryoichi Nagata, MD, PhD, FFPM
(Credit: Satsuma)
According
to an announcement, the FDA has granted approval to Satsuma’s
dihydroergotamine (DHE) nasal powder agent, STS101, marketed as Atzumi,
as a new treatment for patients with acute migraine with or without
aura.1
The company
noted that the nasal powder is not indicated for the preventive
treatment of migraine or for the management of hemiplegic migraine or
migraine with brainstem aura. In addition, the most common adverse
events (AEs) reported with the agent were rhinitis, nausea, altered
sense of taste, application site reaction, dizziness, vomiting,
somnolence, pharyngitis, and diarrhea.
STS101 is
delivered through a specialized, optimized device, otherwise known as
the STS101 delivery device, which ensures consistent and accurate
dosing. Per the medication’s label, patients can self-administer up to 2
doses of STS101 (5.2 mg per dose) within 24 hours, offering flexibility
based on the severity of their migraine attacks. The nasal delivery,
seen as an advantage over oral treatments, ensures faster onset of
action, which is critical for treating migraines quickly.
“The
approval of Atzumi is a milestone to celebrate, providing a new option
for the acute treatment of migraine combining long-proven benefits of
DHE with a patient-friendly and easy-to-use delivery system developed
based on SNBL’s novel intranasal drug delivery platform technology,”
Ryoichi Nagata, MD, PhD, FFPM, president and CEO at Satsuma, said in a
statement.1 “We believe that Atzumi will
contribute to improving the quality of life of patients struggling for
relief from these highly disabling problems.”
With the approval, it becomes the third drug marketed this year for the treatment of migraine, following the approvals of AXS-07 (Symbravo; Axsome Therapeutics) and CT-132 (Click Therapeutics).
STS101 is considered a DHE treatment, which have been used to treat
various forms of vascular headaches, including migraines, for years. DHE
works by acting on serotonin (5-HT0 receptors in the brain,
particularly 5-HT1B and 5-HT1D receptors. This class of medications are
still commonly used to treat acute migraines, especially when triptans
are ineffective, contraindicated, or are not tolerated.
STS101’s
original new drug application (NDA) submission, accepted for review in
May 2023, was met with a complete response letter (CRL) by the FDA.2
At the time, the agency raised no concerns with the clinical trial
results presented; however, the agency did provide comments related to
the formulation of the drug and its manufacturing. After several months,
which included a Type A meeting with the FDA, Satsuma resubmitted the NDA, believing that it addressed all outcomes in the CRL.3
The
original submission was based on findings from the phase 1 comparative
pharmacokinetic and safety trial (NCT03874832) and the phase 3 ASCEND
trial (NCT04406649). Although not required for the application, the
results from the phase 3 SUMMIT trial (NCT04406649) were also
considered. In SUMMIT, STS101 demonstrated a numerical, but not
statistically significant difference vs placebo on the coprimary end
points of freedom of pain and freedom from the most bothersome symptom
(MBS) at 2 hours post dose.
“DHE plays a unique
clinical role in the acute treatment of migraine, providing patients
long lasting effects and the unique ability to provide benefit even when
taken late in a migraine attack. The convenience of Atzumi, the only
DHE nasal powder, will offer patients ease of use combined with
the important known DHE clinical advantages”, Stewart J. Tepper,
M.D., vice president of the New England Institute for Neurology and
Headache, said in a statement.1
READ MORE: Switching Between Anti-CGRP Monoclonal Antibodies Reduces Headache Days in Nonresponders
The
ASCEND trial was a multicenter, open-label safety study involving 480
participants. Of these, 466 individuals self-administered at least one
dose of STS101 or STS101Mk1 (the latter using a first-generation
delivery device), with the study medication transitioning from STS101Mk1
to STS101 in early 2021. The trial found no significant safety or
tolerability issues with the nasal or systemic use of STS101 (n = 344).
Only 4.1% of participants discontinued because of AEs, and no unexpected
serious treatment-related AEs were reported.4
Among
172 participants treated exclusively with STS101, 34.2% achieved
freedom from pain within 2 hours of treatment, and 53.4% achieved
freedom from most bothersome symptom (MBS) at the same time point.
Additionally, over 81% of participants did not require a second dose
within 48 hours of the initial dose. Patients could administer up to two
5.2 mg doses in 24 hours, with a maximum of 12 doses per month over the
course of a year, and were restricted to two or fewer additional
migraine treatments. The average age of participants was 39 years, with
89% being women and 84% being Caucasian.
During the
study, 7.3% of participants (n = 20) discontinued treatment due to AEs,
with 2.9% (n = 8) reporting nasal AEs. The most commonly reported AEs
were nasal discomfort (13.9%), dysgeusia (7.7%), and nasal congestion
(6.2%). Serious AEs, such as postural orthostatic tachycardia syndrome
and cholecystitis, occurred in one individual each but were not
considered related to the treatment. The introduction of the optimized
STS101 device midway through the trial did not affect AE rates or
severity.
References at link.
