CVT-301 for the treatment of Parkinson’s disease

ABSTRACT

Introduction: For patients with Parkinson’s disease (PD), the treatment of motor and nonmotor fluctuations is tantamount to maintaining quality of life. Subcutaneous apomorphine has been the only commercially available rescue therapy for the treatment of OFF episodes. In December 2018, CVT-301 (Inbrija), an inhaled formulation of levodopa (LD), was approved by the FDA for this indication.

Areas covered: In this review, the authors summarize the armamentarium available to address motor fluctuations in PD, including medications in development. The authors discuss the pharmacological properties of CVT-301 as well as its efficacy and safety as reported in phase I, II, and III studies.

Expert opinion: More than 20 medications or surgical procedures are available or in development to address motor fluctuations in PD. Deep brain stimulation (DBS) is an invasive but effective intervention at the end of the treatment spectrum. Less invasive therapies are used in combination to ameliorate motor fluctuations. Rescue therapies can help patients taking oral medications who experience delayed onset symptom relief (delayed ON), and unexpected wearing OFF by providing rapid and durable symptoms relief. CVT-301, an inhaled LD formulation, provides a safe and effective delivery mechanism that may be preferred by patients over subcutaneous injections.

KEYWORDS:

• Parkinson’s disease
• CVT-301
• levodopa
• inhaled levodopa

Article highlights

• With time, patients with Parkinson’s disease develop motor fluctuations including sudden OFF periods and delayed ON periods.

• Rescue medications, such as subcutaneous apomorphine, provide a rapid onset of action to treat these types of motor fluctuations.

• CVT-301 was approved by the FDA in December 2018 as a rescue medication.

• CVT-301 is an inhaled levodopa (LD) formulation that can provide rapid onset (10 min) of improvement in UPDRS part III scores.

• In a phase III clinical study (SPAN PD) and subsequent follow-up safety studies, CVT-301 proved effective and well tolerated.

• Common adverse events included cough, nausea, upper respiratory tract infection, and sputum discoloration.

• One CVT-301 capsule will contain 42 mg of LD.

• Patients will inhale the contents of two capsules, as needed, up to 5 times per day for the treatment of OFF periods.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Information resources

The interested reader is directed to the Acorda Therapeutics Inbrija homepage: https://www.inbrija-hcp.com. There, the package insert is available and provides indications, dosing instructions, contraindications, and adverse reactions. The primary sources of the Phase I, II and III trials are referenced in this manuscript and can be read for further details beyond those provided in this review.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.