Due to the growing popularity of new competing therapies for acute migraine treatment, novel reformulations of dihydroergotamine (DHE) such as Satsuma Pharmaceutical’s lead product STS101 and Pulmatrix’s PUR3100, which are both powder-based formulations, may struggle to find a competitive edge over oral gepants and oral ditans, says GlobalData, a leading data and analytics company.

Christie Wong, Pharma Analyst at GlobalData, comments: “DHE is currently available as a nasal spray or for injection subcutaneously, intramuscularly, or intravenously. However, key opinion leaders (KOLs) previously interviewed by GlobalData noted that although DHE can reverse central sensitization and provide long-acting headache relief, it was rarely used due to its unfavorable side effect profile. Furthermore, the DHE liquid nasal sprays on the market have a burdensome administration process that does not always translate to migraine relief.”

The dry powder formulations of intranasal STS101 and orally inhaled PUR3100 aim to remedy this by improving the bioavailability of the drug, which may translate into faster-acting relief for patients. Generally, orally and intranasally inhaled drug formulations can offer a more rapid onset of action than oral medication, as they bypass the small bowel gastrointestinal tract absorption, which is often significantly delayed during a migraine episode.

Wong adds: “Timely treatment to relieve a migraine is essential as it enables patients to return to their normal routine and may lessen the need for additional pain medication. If STS101 and PUR3100 are shown to provide rapid headache relief, they may be a desirable option—particularly among patients who suffer from nausea or dysphagia and are unable to take an oral pill.”

Despite these advantages, there are a number of obstacles ahead for these products. Firstly, the expansion of the oral gepant drug class has transformed the migraine space in recent years as they are well tolerated and exhibit both acute and preventive properties for migraine treatment, reducing the number of monthly migraine days. As such, prescribers and patients may prefer gepants, due to their dual acute and prophylactic effects, over a DHE reformulation with only acute effects.

Wong notes: “As gepants and lasmiditan do not exhibit vasoconstriction of the cerebral, coronary, and peripheral arteries, they can be used in patients who are at risk of cardiovascular problems. In contrast, DHE is contraindicated in this patient cohort.”

Furthermore, intranasal formulations tend to have a higher annual cost of therapy in comparison to oral formulations. For example, the average cost per treatment day of Impel NeuroPharma’s Trudhesa (DHE nasal spray) is at a 200% premium over Biohaven’s oral gepant, Nurtec (rimegepant).

Wong continues: If the dry powder formulations of STS101 and PUR3100 are priced in line with Trudhesa, the premium pricing may act as another barrier for its uptake.”

A further competitive threat to future DHE dry powder formulations is the arrival of a new intranasal generation of gepant set to enter the market soon; Biohaven’s zavegepant is currently in pre-registration in the US for the acute treatment of migraines and GlobalData forecasts that it will launch in the US in Q3 2023, where it has the potential to be the first intranasal gepant for acute migraine treatment.

Wong concludes: “Should STS101 and PUR3100 eventually receive FDA approval, Satsuma Pharmaceutical and Pulmatrix will need to provide strong efficacy data, solid marketing, and competitive pricing to set them apart from competitors and convince payers to reimburse them.”