Parkinson's patients no longer need to rely on a needle for apomorphine antidote for 'off' episodes after new FDA approval
A morphine derivative — usually injected or infused — used to treat “off” episodes in Parkinson’s is now up for grabs in a convenient under-the-tongue dissolvable formulation, making life much easier for patients when flares strike.
Sunovion, a company formed in 2009 by the fusion of Sepracor and the US operations of Sumitomo Dainippon Pharma, has secured the approval of the sublingual formulation about a year and a half following an initial rejection by the FDA.
The drug, known chemically as apomorphine, is a dopamine agonist. Parkinson’s, a chronic neurodegenerative disease, occurs due to the loss of dopamine-producing cells. Despite standard therapy with oral levodopa/carbidopa, within the first four to six years after diagnosis up to 60% of patients experience “off” episodes, which are characterized by tremor, stiffness, slowed movement or other motor symptoms.
Branded as Kynmobi, the formulation is the first and only sublingual therapy for acute use in “off” episodes associated with Parkinson’s — it can be used up to five times a day. The formulation is set to launch by September.
The FDA approval was based on a 109-patient placebo-controlled study. Data showed Kynmobi induced significant improvements in motor symptoms at 30 minutes after dosing at week 12, with a mean reduction of 7.6 points, compared to placebo, on a key Parkinson’s disease rating scale. However, nearly a third of patients (9 out of 54 on the Kynmobi arm) discontinued treatment primarily because of oropharyngeal (the part of the throat just behind the mouth) side-effects.
Until now, apomorphine was approved for use packaged as a pre-filled disposable pen to be injected as needed, or as an infusion given over a period of several hours via a portable, battery-driven pump using a pre-filled syringe or from glass vials called ampoules.
Sunovion got its hands on the formulation by acquiring the biotech Cynapsus Therapeutics at a premium — paying $624 million in cash at $40.50 per share in 2016, twice the value of the Toronto-based company’s shares on the day. And despite posting positive late-stage data on the formulation in 2018, the FDA rejected its marketing application in 2019. The agency requested more information and analyses, although the company said no new clinical studies were required.
Aquestive Therapeutics, which is focused on developing less-invasive drug delivery technology, entered into a license agreement with Cynapsus Therapeutics in 2016. With the approval of Kynmobi, the New Jersey-based company is eligible to get royalties on sales.
A company in neighboring New York called Acorda Therapeutics launched an inhaled version of levodopa in February last year after the FDA approved the therapy, branded Inbrija, in late 2018 for ‘off’ episodes experienced by Parkinson’s patients.