STS101 (dihydroergotamine mesylate (DHE) nasal powder) for the acute treatment of migraine is Satsuma Pharmaceuticals’ lead product candidate. STS101 incorporates proprietary dry-powder nasal formulation and delivery device technologies invented, developed and optimized over more than 15 years by a dedicated team at Japan-based Shin Nippon Biomedical Laboratories, Ltd. to enable rapid absorption and high bioavailability of drugs delivered via the nose with quick, intuitive and patient-friendly self-administration.
We specifically designed STS101 to be a reliable and convenient DHE product capable of delivering the therapeutic advantages of DHE while overcoming the shortcomings and limitations of injectable and liquid nasal spray DHE products.
STS101 Key Attributes
During our Phase 1 clinical trial, STS101 demonstrated a number of key attributes that we believe may provide significant advantages over existing acute treatments for migraine and result in robust and consistent clinical performance and thereby facilitate broad STS101 adoption and use, if approved. These attributes are primarily the result of the proprietary STS101 dry-powder formulation, which incorporates a mucoadhesive drug carrier and engineered drug particle technologies, and the proprietary STS101 nasal delivery device:
- Rapid (within 10 minutes) and sustained achievement (for over 2.5 hours) of drug plasma levels that are greater than the target drug plasma concentration (1 ng/ml) we estimate is minimally necessary for DHE therapeutic response
- Low pharmacokinetic variability
- Quick and convenient self-administration within a matter of seconds
Simple, Quick & Intuitive Administration
DHE Therapeutic Advantages:
Long treatment window following migraine onset with minimal attenuation of effect with late treatment. It is estimated that the opportunity for early treatment is possible in only ~50% of migraine attacks. The efficacy of triptans and other migraine drugs depends on treatment early during the course of a migraine attack and has been shown to decrease with time from onset of the attack.1
Low risk of 24+ hr headache recurrence. Migraine recurrence occurs within 24 hours in up to 45% of triptan-treated attacks. In controlled comparative clinical studies with triptan therapy, DHE demonstrated 24-hour migraine recurrence significantly lower than triptans.2
Effective in migraine with allodynia. Allodynia, which is present in up to 2/3 of all migraine attacks, refers to central pain sensitization (increased response of neurons) following normally non-painful, often repetitive, stimulation. Allodynia can lead to the triggering of a pain response from stimuli which do not normally provoke pain, such as brushing hair or showering, resting one’s head on a pillow, or exposure to heat or cold. In migraine attacks with allodynia, triptans and most other drugs are poorly effective. However, DHE has demonstrated effectiveness irrespective of the presence of allodynia.3
Effective in triptan non-responders. Athough oral triptans are a mainstay treatment for migraine, ~40% of patients with migraine treated with oral triptan therapies do not respond to treatment, and up to 80% do not achieve sustained freedom from pain. ~50% of triptan non-responders have been shown to respond to treatment with DHE.4
Low risk of medication overuse headache. Unlike triptans and other migraine therapies, the labels of which caution against use on 10 or more days per month due to risk of headache exacerbation referred to as medication overuse headache, DHE is thought to have a lower risk for causing medication overuse headache than triptan class therapies.5
Limitations and Shortcomings of Injectable and Liquid Nasal Spray DHE Products
DHE is marketed in the U.S. as a solution for injection (intravenous (IV), intramuscular or subcutaneous). However, injections are invasive, painful, and not a preferred route-of-administration for many people with migraine. IV injection of DHE, although effective, is associated with a higher frequency of side effects, including nausea and vomiting, increases in blood pressure, than other routes of DHE administration due to the very high plasma drug levels that are rapidly achieved following IV administration. IV DHE administration typically requires pre-treatment with IV anti-nausea medication and is generally performed by a healthcare provider in the clinical or hospital setting using specialized equipment.
A liquid nasal spray formulation of DHE was approved in the U.S. in the 1990s on the basis of clinical studies that were not designed in accordance with current FDA guidance documents for the development of drugs for the acute treatment of migraine. The DHE liquid nasal spray product requires assembly, priming, and administration of 4 sprays (2 per nostril 15 minutes apart) to deliver a full dose of DHE. Following administration of the liquid nasal spray product, drug plasma levels are both highly variable and slow to reach the target drug plasma concentration (1 ng/ml) we estimate is minimally necessary for DHE therapeutic response.
1 Tepper, S et al., MAP0004, Orally Inhaled Dihydroergotamine for Acute Treatment of Migraine: Efficacy of Early and Late Treatments, Mayo Clin Proc. 2011. (Pubmed link: https://www.ncbi.nlm.nih.gov/pubmed/21964172)
2 Winner, P et al., A Double-blind Study of Subcutaneous Dihydroergotamine vs Subcutaneous Sumatriptan in the Treatment of Acute Migraine, Arch. Neurol. 1996. (Pubmed link: https://www.ncbi.nlm.nih.gov/pubmed/8639069)
3 Tepper, S et al., Efficacy and Safety of MAP0004, Orally Inhaled DHE in Treating Migraines With and Without Allodynia, Headache 2012. (Pubmed link: https://www.ncbi.nlm.nih.gov/pubmed/22106843)
4 Fisher, M et al., Dihydroergotamine nasal spray for relief of refractory headache: a retrospective chart review, Curr Med Res Opin. 2007. (link: https://www.tandfonline.com/doi/abs/10.1185/030079907X178883)
5 Saper, JR et al., DHE in the pharmacotherapy of migraine: potential for a larger role, Headache 2006. (Pubmed link: https://www.ncbi.nlm.nih.gov/pubmed/17078853)
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