Parkinson’s Niche To Expand With New Drugs, More Patients

Newron’s new Parkinson’s disease therapy, Xadago, approved in the US after a regulatory delay, is expected to be the first of several new products to be introduced in this long-neglected therapeutic sector.

The US approval of Newron Pharmaceuticals SPA’s add-on Parkinson’s disease therapy, Xadago (safinamide), announced March 21, may have been welcomed by that company’s investors, but after nearly a decade with few if any new products, the therapeutic niche is rapidly becoming more competitive, with several new products nearing the market.

Italy’s Newron, headquartered near Milan but listed on Switzerland’s SIX stock exchange, has seen its share price increase by 22% in the past month to CHF27.5 ($27.8) per share, more than likely in anticipation of the FDA approval of Xadago on or near the PDUFA date of March 21, 2017, a date achieved by the regulator.

Xadago is the first new chemical entity approved for Parkinson’s disease in the US for more than 10 years, and the US sublicensee, US WorldMeds LLC, said it would accelerate its US launch preparations to make the product available to patients. US WorldMeds is a Kentucky-based specialty pharmaceutical company that sublicensed US marketing rights for Xadago from Newron’s development partner, the fellow Italian specialty company, Zambon SPA.

But the US approval of Xadago comes two years after its European approval, and a year later than originally anticipated in the US, and competing products are nearing the market. These include Acorda Therapeutics Inc.’s CVT-301, an inhalable formulation of levodopa, for which a US NDA submission is planned for the second quarter of 2017, and a European filing by the end of 2017. The drug has shown a statistically significant improvement in motor function in patients have off periods.

And in 2016, Acordia acquired Biotie Therapies Corp. and with it that company’s adenosine 2A receptor inhibitor tozadenant, currently being evaluated in a Phase III study for improving motor function and activities of daily living in people with Parkinson’s disease; the study should be completed by the end of 2017.

Analysts at Jefferies estimated that peak sales of Xadago could reach $700m worldwide, around $430m of which are expected to be in the US. It should be used in around 15% of moderate-to-severe Parkinson’s disease patients on L-dopa in the US, 20% in Europe and 2.5% in the rest of the world, the analysts estimate.

FDA Concerns About Abuse Potential

Although introduced in Germany in 2015 and in Italy, Spain, the UK, Belgium, Denmark, Sweden, Luxembourg, the Netherlands, Norway and Switzerland in 2016, progress in the key US market for Xadago has previously been thwarted by FDA concerns, the most recent being about its risk of abuse and the development of dependence, outlined in a complete response letter in March 2016.

Newron convinced the FDA that new clinical studies were not necessary, and that data from preclinical abuse liability studies and clinical data analyses were sufficient. The company then resubmitted the NDA in Oct. 2016, with a PDUFA date of March 21, 2017.

The US is the largest market for Parkinson’s therapies, with around one million patients with the disease, and that number is expected to grow in the future in line with the aging of the susceptible elderly population. Although there are effective therapies for Parkinson’s disease, many of which are generic, there is still an unmet need to shorten the “off” time – the time when levodopa therapy is ineffective – during which patients experience motor fluctuations such as tremor.

Xadago, a dual MAO B-inhibitor and glutamate release inhibitor, was approved in the US for the treatment of Parkinson’s disease as add-on therapy to levodopa/carbidopa.

According to analysts at Datamonitor Healthcare, the Parkinson’s disease market was worth around $2.8bn in the US, Japan, and the five major US markets in 2014, but is expected to increase to $3.4bn by 2023, driven by products such as Xadago that decrease patients’ off-time on levodopa.

In a statement issued March 21, Newron’s chief medical officer, Ravi Anand, pointed out that Xadago significantly improves on time, off time and parkinsonism compared with standard of care without increasing time spent with dyskinesia in patients experiencing motor fluctuations while on optimized levodopa/carbidopa therapy.