Levodopa

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Articles

New Medicines

Inbrija · Parkinson's disease - adjunctive treatment to oral levodopa for 'off episodes'

Information

Inbrija
New formulation
Acorda
Acorda

Development and Regulatory status

Licensed but not launched
Licensed but not launched
Launched
Feb 20 · UK launch delayed. According to the latest annual report, Acorda is in discussions with potential partners regarding the distribution of Inbrija outside of the US, with potential partners in Europe and Japan [19].
Sep 19 · Approved in the EU [18]
Jul 19 · Recommended for EU approval by CHMP - the full indication is "for the intermittent treatment of episodic motor fluctuations (off episodes) in adult patients with Parkinson’s disease (PD) treated with a levodopa/dopa-decarboxylase inhibitor.” [17].
Mar 19 · Acorda submits responses to the Day 120 list of questions related to the MAA for Inbrija, and expects final decision from European Commission by end 2019 [16].
Feb 19 · Acorda has been in discussions with potential partners regarding Inbrija outside of the US [15].
Jan 19 · Launched in US [14].
Dec 18 · Approved in the US for for intermittent treatment of OFF episodes in people with Parkinson’s taking carbidopa/levodopa. Launch is planned for Q1 2019 [13].
Sep 18 · Approval deadline in the US extended to Jan 2019 [11].
Mar 18 · Filed in the EU. Acorda plas to seek a partner for the commercialization of INBRIJA in ex-US territories [10].
Feb 18 · Filed in US. FDA has set a target date of 5/10/18 [9].
Oct 17 · Acorda Therapeutics plans to re-submit NDA in Q4 17 & file in EU in H1 18 [8].
Aug 17 · Acorda have received a ´Refusal to File´ letter from the FDA for Inbrija, with questions raised about its manufacturing readiness. The company believes the issues raised are addressable [7].
Jun 17 · Acorda submit NDA to FDA. Application includes data from PIII SPAN-PD study (NCT02240030) and two long-term safety studies [6].
Feb 17 · Acorda announces that the PIII trial (NCT02240030) achieved its endpoints and that they anticipate filing for marketing approval in the US during Q2 2017; they also plan to seek marketing authorisation in Europe by the end of 2017 [4]. Patients in the trial have been offered continued participation in a follow-up study (NCT02242487) and a further multi-national open-label PIII study comparing outcomes to usual treatment continues [5].
Dec 14 · Acorda Therapeutics expects to file an NDA in the US by end of 2016 [3].
Dec 14 · First patient enrolled in a PIII study of CVT-301 for treatment of OFF episodes in Parkinson’s disease [1].

Category

An inhaled formulation of levodopa. It is being developed using ARCUS platform, which utilises a proprietary dry powder and inhaler combination to deliver a large, precise dose to the deep lung for rapid, predictable and consistent absorption.
The incidence of the disease rises steeply with age; from 17.4 in 100,000 person years between 50 and 59 years of age to 93.1 in 100,000 person years between 70 and 79 years. Prevalence is 65.6 per 100,000 to 125 per 100,000 [2].
Parkinson's disease - adjunctive treatment to oral levodopa for 'off episodes'
Inhalation

Trial or other data

Jan 19 · Results of NCT02240030 (n=498) published in the Lancet [12].
Feb 17 · Top-line results from NCT02240030 announced - the study achieved its primary outcome and patients on the high dose showed a UPDRS score of 9.83 vs. 3.91 for placebo [4]. Two PIII trials remain in progress to deliver additional data on safety: NCT02352363 is a randomised open label study comparing CVT-301 with usual care, with a primary outcome of pulmonary safety assessed by spirometry, and NCT02242487 is a follow-on study primarily for patients who have participated in previous CVT-301 trials and also having pulmonary safety as the primary outcome [5].
Mar 15 · Cynapsus Therapeutics plans to file in the US in 2016
Dec 14 · PIII (NCT02240030) trial begins. It is expected to enrol approximately 345 participants across three arms: 50mg, 35mg, or placebo. These are the same doses used in the Phase 2b study. The primary outcome measure is improvement on the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III after administration of CVT-301 [1].
Dec 14 · Positive results from a CVT-301 P2b study presented at the 2014 American Academy of Neurology Annual Meeting. In this study, participants receiving CVT-301 showed a statistically significant and clinically important reduction in average UPDRS Part III motor score versus placebo across time points beginning at 10 and up to 60 minutes post-administration (p < 0.001). Both doses of CVT-301 were well tolerated, with no increase relative to placebo in troublesome or non-troublesome dyskinesias during ON periods. There were no serious adverse events in the trial, and the incidence of drug-related adverse events was similar between treatment groups. The CVT-301 inhaler was shown to be easily self-administered in the OFF state [1].

Evidence based evaluations