CVT-301’s positive Phase III data mean an approval is almost certain – and that fluctuating Parkinson’s disease patients could soon benefit from a new rescue therapy. This inhalable therapy’s fast onset of action and less invasive route of administration give it an edge over available injectable apomorphine formulations. While the sublingual apomorphine product APL-130277 could be a potential threat, CVT-301’s earlier launch should secure it a place in treatment practices. Assuming Acorda employs a competitive pricing strategy, CVT-301 has good chances of being well received by payers, physicians, and patients alike.
On 9 February 2017, Acorda Therapeutics announced positive results from the SPAN-PD study (ClinicalTrials.gov identifier: NCT02240030), a 12-week, placebo-controlled, Phase III trial studying CVT-301 (levodopa) for the treatment of motor fluctuations in Parkinson’s disease. CVT-301 led to statistically significant improvements in Unified Parkinson’s Disease Rating Scale – Part 3 (UPDRS III) score relative to placebo, which was the trial’s primary endpoint. Furthermore, CVT-301’s safety profile remained consistent with earlier trials, with no notable pulmonary safety signals emerging during the Phase III study. Datamonitor Healthcare expects these findings will be confirmed by CVT-301’s two remaining ongoing long-term safety trials, from which topline results are due by the end of Q1 2017.
Following the positive Phase III data, Acorda reiterated its plans to file CVT-301 for approval in the US during the second quarter of 2017, while a regulatory filing in the EU is expected by the end of 2017, pending further data analyses. Datamonitor Healthcare believes that CVT-301 is well positioned to become the new rescue therapy of choice to treat “off” periods in fluctuating Parkinson’s disease patients. Its fast onset of action and less invasive route of administration give it an edge over injectable apomorphine formulations such as Apokyn (apomorphine; Britannia Pharmaceuticals/Kyowa Hakko Kirin). The major threat to CVT-301’s use as a rescue therapy should be Dainippon Sumitomo/Sunovion’s sublingual APL-130277 (apomorphine). Despite this, CVT-301’s expected earlier launch should enable it to claim a place as the rescue therapy of choice for fluctuating Parkinson’s disease patients.
An inhalable levodopa formulation could avoid delays in absorption and allow for a fast onset of action
CVT-301 is an inhaled formulation of levodopa, in development as an adjunct to existing oral levodopa formulations in patients experiencing motor fluctuations. While levodopa remains the gold standard across all stages of Parkinson’s disease, disease progression is associated with the onset of peaks and troughs in levels of the molecule. These lead to “off” periods in which there is inadequate motor control, as well as peak-dose dyskinesia, where patients display drug-induced involuntary movements. CVT-301 is designed to supplement existing levodopa treatment through as-needed self-administration, returning patients to an “on” state without inducing dyskinesia. The inhalable administration route allows levodopa to bypass the digestive system, avoiding delays in absorption and meaning that levodopa quickly reaches the brain.
Phase III trial confirms earlier positive Phase IIb data
CVT-301’s single Phase III pivotal trial, SPAN-PD, was a placebo-controlled study investigating the effects of two different doses (60mg and 84mg) on the motor function of fluctuating Parkinson’s disease patients. All patients were receiving a stable oral regimen of carbidopa/levodopa, and CVT-301 was self-administered up to five times daily for 12 weeks, working as a rescue treatment for patients experiencing “off” periods.
In the SPAN-PD trial, CVT-301 84mg led to a reduction of 9.83 points in UPDRS III score compared to a reduction of 5.91 points with placebo (p=0.009). No major safety concerns were identified during the study, and pulmonary tests revealed no notable safety signals. While cough was reported with both CVT-301 doses, it was usually mild. Only three out of the 227 patients treated with CVT-301 discontinued the study due to this adverse event. The table below displays the most common adverse events seen in the trial (those with a frequency above 5%).
Acorda is targeting a key unmet need in Parkinson’s disease with CVT-301
Acorda clearly understands the unmet needs in Parkinson’s disease, and where some of the market’s major commercial opportunities lie. Despite the longstanding role of levodopa in Parkinson’s disease treatment, motor complications remain the most important limitation to its long-term use – it is estimated that 50–80% of patients develop response fluctuations after five to 10 years of levodopa treatment. These commonly include the so-called “wearing off” episodes, where motor symptoms re-emerge before a patient’s next scheduled dose. “Off” periods can severely impact patients’ quality of life, and few therapies have been shown to address them both effectively and quickly. Acorda is therefore targeting an area of high unmet need with CVT-301, and could very well benefit from the sparse competition.
CVT-301 could become the rescue therapy of choice for fluctuating Parkinson’s disease patients experiencing “off” episodes
Some of the current options used to avoid motor fluctuations include an increase in the frequency of administration of levodopa doses, or the use of the carbidopa/levodopa pump Duopa (AbbVie) that allows for a continuous administration and stabilizes levodopa levels. Both strategies have limitations: while the first increases patients’ pill burden, Duopa requires an initial surgical intervention and can be associated with infections. An additional option involves the as-needed use of an injectable apomorphine formulation, such as Apokyn. This subcutaneous injectable dopamine agonist is delivered by a metered pen, and benefits from a quick onset and short-term duration of action. In this setting, Apokyn is expected to compete directly with CVT-301, but Acorda’s drug should have the upper hand. Instead, Datamonitor Healthcare believes that the major threat to CVT-301’s use as a rescue therapy could come with APL-130277’s potential approval. This sublingual apomorphine formulation is also expected to be fast-acting, and its oral delivery method should be patient-friendly. As APL-130277 is expected to be filed for approval in the US during the first half of 2017, Acorda will need to move fast. Overall, Datamonitor Healthcare believes that CVT-301’s expected earlier filing should enable the experienced Acorda to effectively position its drug as the rescue therapy of choice for fluctuating Parkinson’s disease patients experiencing “off” episodes.
Acorda Therapeutics (2017) Acorda Announces Positive Phase 3 Clinical Trial Results for CVT-301. Available from: http://ir.acorda.com/investors/investor-news/investor-news-details/2017/Acorda-Announces-Positive-Phase-3-Clinical-Trial-Results-for-CVT-301/default.aspx [Accessed 9 February 2017].