In September, Satsuma Pharmaceutical announced positive Phase III trial results for its lead product STS101 and Pulmatrix concluded subject dosing in a Phase I clinical trial for PUR3100. Both pipeline products are novel powder formulations, with STS101 administered intranasally and PUR3100 inhaled orally, in development to improve the absorption rate of the active molecule, dihydroergotamine (DHE), and to thus provide more rapid headache relief. DHE is currently available as a nasal spray or for injection subcutaneously, intramuscularly, or intravenously. However, due to the growing popularity of new competing therapies for acute migraine treatment, including oral gepants and oral ditans, questions arise whether there is a demand in the market for additional DHE reformulations.
For the past two decades, oral triptans have been considered the industry gold standard to relieve migraine headaches. 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.
However, the dry powder formulations of STS101 and 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. Timely treatment to relieve the migraine headache is essential as it enables patients to return to their normal routine and may lessen patients’ requirement for additional pain medication. As such, 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.
But 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. Furthermore, DHE is contraindicated in patients who are at risk of cardiovascular problems. As gepants and lasmiditan do not exhibit vasoconstriction of the cerebral, coronary, and peripheral arteries, they can be used in this patient cohort.
Additionally, KOLs noted that patient uptake of intranasal formulations is often low due to the side effects invariably present with nasal sprays that are unrelated to the medication. This includes symptoms of post-nasal drip and congestion. In addition, inhaled products can leave an unpleasant taste that deter their usability. Whether the dry powder formulations will prove different is still unknown. Furthermore, intranasal formulations tend to have 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 priced at a 200% premium over Biohaven’s oral gepant, Nurtec (rimegepant). 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 migraine. GlobalData forecasts its launch in the US in Q3 2023, where it has the potential to be the first intranasal gepant for acute migraine treatment. Thus, 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.