A 10-year wait obviously didn’t discourage Kyowa Kirin from changing the FDA’s mind for its add-on Parkinson’s disease therapy.
Tuesday, the FDA finally approved the Japanese pharma’s istradefylline, to be marketed under the brand Nourianz, as an add-on treatment to levodopa/carbidopa. It’s designed to help Parkinson’s patients whose medications are not working well control symptoms such as tremor and difficulty walking, known as “off” episodes.
The drug has been sold in Japan since 2013 but was previously rejected by the FDA in 2008. At that time, the agency raised concerns about its efficacy and asked for more data.
Known as Nouriast in Japan, the Parkinson’s drug has been cited by Kyowa Kirin as an important top-line contributor in its home country. The drug raked in 4.8 billion yen ($45.4 million) Japanese sales in the first half of 2019, up 400 million yen over last year. The company now expects it could reach 10 billion yen for the whole year in Japan.
“Today's FDA approval of Nourianz is an important milestone and provides U.S. patients with a novel non-dopaminergic once-a-day oral treatment option to be used in conjunction with levodopa/carbidopa for Parkinson’s disease,” Kyowa Kirin’s U.S. president, Tom Stratford, said in a statement.
Kyowa Kirin once signed on Valeant to market Nourianz in North America, but the licensee in 2011 changed its mind after an R&D model review. Now, Kyowa Kirin will navigate the launch all by itself.
Nourianz targets the adenosine A2A receptors, which work with neuromodulator adenosine. The receptors are found in the brain’s basal ganglia, whose abnormality is noted in Parkinson’s.
The adenosine A2A receptor antagonist idea had its fair share of failures, too. In 2010, Vernalis and partner Biogen halted development of their candidate vipadenant after toxicity concerns were noticed in preclinical studies. Then, in 2013, Merck & Co. threw in the towel with preladenant after a preliminary review of data from late-stage trials found it didn’t work well enough. Most recently, in 2017, Acorda Therapeutics ditched tozadenant—which it acquired via its $363 million Biotie takeover—after patient deaths in phase 3.
The FDA based its decision on results from four clinical studies on a total of 1,143 participants already taking levodopa/carbidopa. In those trials, patients who got Nourianz experienced a statistically significant decrease in daily “off” time compared with those receiving placebo, the agency said. However, in one phase 3, the drug only showed a trend toward additional daily “off” time reduction benefit over placebo but didn’t cross the statistically significant bar, the company revealed in late 2016.
As requested by the FDA, patients should be monitored for dyskinesia, or involuntary muscle movement, while on Nourianz. In clinical trials, 1% of patients treated with either 20 mg or 40 mg dose discontinued treatment because of dyskinesia, while none in the control arm suffered from it
The company also has another adenosine A2A receptor antagonist, KW-6356, that’s now in phase 2 development in Parkinson’s disease, even though Lundbeck last year terminated a licensing agreement for the drug’s ex-Asia rights.