Kyowa Kirin Stops KW-6356 Program Despite Promising Results
Decision based on global regulatory, development, and logistical hurdles
Kyowa Kirin has discontinued the clinical development of its investigational treatment, KW-6356, for Parkinson’s disease, despite Phase 2 clinical trial data showing promising results as a monotherapy or in combination with levodopa.
The decision was based on the “global regulatory landscape, development hurdles, and timelines for potential market entry,” according to a company press release.
In Parkinson’s, loss of the neurons that release dopamine, a chemical messenger that allows for communication between nerve cells, results in many of the symptoms associated with the disease. As such, many therapies for Parkinson’s focus on increasing the levels of dopamine.
KW-6356, as well as its predecessor, Nourianz (istradefylline), was designed with a different strategy in mind. It blocks the adenosine A2A receptor, a receptor found in a region of the brain that controls movement. The binding and blocking of this receptor triggers the release of gamma amino-butyric acid (GABA), another chemical messenger involved in nerve signaling and motor function.
Nourianz is Kyowa’s first-generation adenosine A2A antagonist developed as an add-on medication to treat off episodes — symptom flares between scheduled doses of a medication — in patients on a carbidopa/levodopa regimen. It was approved by the U.S Food and Drug Administration in 2019 and has been available in Japan since 2013. However, this medication’s development was discontinued in Europe.
KW-6356’s safety and efficacy was tested in two Phase 2 clinical trials. The first (NCT02939391) included 168 adult Japanese patients with early Parkinson’s who had not previously received any other anti-Parkinson’s medications.
Patients were randomly assigned to receive a low or high dose of KW-6356, or a placebo, for 12 weeks (or three months). The main goal was to assess changes in motor function, determined using the MDS-UPDRS part III (motor assessment), between KW-6356 and placebo groups. Both doses were found to improve motor function compared to the placebo, and no major safety issues were reported.
In the second Phase 2 trial (NCT03703570), also based in Japan, KW-6356’s efficacy was investigated in 502 adult patients with Parkinson’s already receiving treatment with levodopa. Participants were given KW-6356 or a placebo for 26 weeks (about six and a half months).
As before, the researchers aimed to determine changes in MDS-UPDRS part III scores. The study’s secondary goal was to assess changes from baseline in the total hours of awake time per day spent in the off state.
Changes in the KW-6356 group were significantly greater than those in the placebo group, and no major safety problems occurred, according to a company press release in 2020.
Kyowa had speculated that since KW-6356 had a high affinity and selectivity for adenosine A2A receptors, it could obtain approval for wider indications than Nourianz. There are currently no other adenosine A2A antagonist therapies for Parkinson’s in the company’s pipeline.