Civitas Therapeutics Announces Positive Phase 2 Clinical Results for CVT-301, an Inhaled L-dopa for Parkinson’s Disease

  Civitas Therapeutics Announces Positive Phase 2 Clinical Results for
  CVT-301, an Inhaled L-dopa for Parkinson’s Disease

 CVT-301 shown to treat debilitating OFF Episodes Associated with Parkinson’s
                                   Disease

Business Wire

CHELSEA, Mass. -- April 19, 2013

Civitas Therapeutics, Inc., a privately-held pharmaceutical company developing
transformative therapeutics using the ARCUS^(TM) respiratory delivery
platform, today announced positive topline results from a Phase 2 clinical
trial of CVT-301, an inhaled formulation of levodopa (L-dopa). CVT-301 is
being developed as an adjunct therapy to provide rapid and reliable relief
from intermittent debilitating motor fluctuations (OFF episodes) that impact a
large proportion of Parkinson’s disease patients.

The study used a randomized, placebo-controlled design to evaluate L-dopa
pharmacokinetics and pharmacodynamic effects following administration of
CVT-301 to Parkinson’s disease patients experiencing motor fluctuations.
Administering CVT-301 to patients in the OFF state produced a rapid and
durable improvement in motor function. The pharmacokinetic data recapitulated
the Phase 1 study results showing CVT-301 provided immediate L-dopa absorption
and consistent increases in plasma concentrations in marked contrast to the
delayed and variable L-dopa levels seen with Sinemet^® (oral
L-dopa/carbidopa). All doses of CVT-301 were safe and well tolerated with no
increase in the frequency or severity of dyskinesias relative to oral. Civitas
plans to present the comprehensive data from the study at a future scientific
meeting.

“The unpredictable wearing off of oral L-dopa and the dyskinetic side effects
are among the most significant challenges with the current management of
Parkinson's disease," said Dr. Todd Sherer, CEO of The Michael J. Fox
Foundation for Parkinson's Research. "There remains a critical unmet need for
therapies that increase the reliability of L-dopa while not exacerbating the
side effects."

“The significant inherent variability of oral L-dopa absorption is known to be
a major contributor to the development of debilitating OFF episodes,” said Dr.
Martin Freed, Chief Medical Officer and co-founder of Civitas. “CVT-301 has
the potential to provide a transformative benefit to patients by enabling more
predictable and effective symptomatic relief without worsening side effects
such as dyskinesia, thereby allowing them to regain control of their lives.”

“The results of this study represent proof-of-concept of CVT-301 as a therapy
to provide rapid and precise control of patients’ L-dopa levels enabling
better management of their intermittent motor fluctuations. This has the
potential to be a very meaningful advancement in the symptomatic treatment of
Parkinson’s disease,” said Dr. Karl Kieburtz, President of Clintrex LLC, the
Robert J. Joynt Professor of Neurology, University of Rochester, and a member
of the Civitas Scientific Advisory Board.

This Phase 2a study of CVT-301 was funded in part by a grant from The Michael
J. Fox Foundation for Parkinson’s Research.

Trial Design

The Phase 2 study (CVT-301-002) was a multicenter, randomized, double blind,
placebo-controlled, single dose, cross-over design with three arms (placebo,
25mg and 50mg) and included an “open label” oral Sinemet arm. The twenty four
(24) patients treated in this study underwent serial evaluations of L-dopa
plasma levels, motor response, and safety at each visit. The patients were
administered the study drug in the OFF state with the serial evaluations
starting prior to dosing and continuing for up to 180 minutes post-dose. Motor
function was measured using a tapping test, the Unified Parkinson’s Disease
Rating Scale Part III (UPDRS III), and subjective evaluation of “meaningful”
ON and OFF. Safety parameters monitored included pulmonary function, clinical
laboratory data, EGCs, and vital signs (blood pressure, heart rate, and
orthostatic blood pressure). This study was designed to measure the time,
magnitude, and durability of CVT-301’s effect on motor function, to evaluate
the safety and tolerability of CVT-301 in Parkinson’s disease patients, to
confirm the results from a CVT-301 Phase 1 healthy volunteer study
(CVT-301-001), and to establish the dose for future clinical trials with
CVT-301.

About CVT-301

Civitas’ lead program, CVT-301, is an inhaled formulation of L-dopa for the
rapid and reliable relief from debilitating motor fluctuations associated with
Parkinson’s disease. For symptomatic relief, oral L-dopa is administered to
maintain dopamine levels in the brain above the therapeutic threshold; yet the
efficacy of oral L-dopa is significantly compromised by delayed and
unpredictable absorption and excessive variability in the circulating plasma
drug concentrations inherent to the oral delivery route. CVT-301 is an
ARCUS^(TM) therapeutic that incorporates L-dopa and is optimized to deliver a
precise dose to the deep lung for rapid and predictable L-dopa absorption. The
ARCUS^(TM) platform is able to uniquely deliver the necessary L-dopa dose with
the required precision. CVT-301 is being developed as an adjunct to standard
oral L-dopa therapy to enable patients to manage motor fluctuations caused in
part by the inter-dose variability of oral L-dopa. In preclinical models,
CVT-301 has demonstrated immediate and consistent increases in L-dopa peak
plasma concentration providing rapid, durable symptomatic relief, even when
compared to larger doses of oral L-dopa. A Phase 1 study in healthy volunteers
showed that CVT-301 rapidly achieved target L-dopa plasma levels with a
pharmacokinetic profile supportive of its therapeutic potential.

About Parkinson’s Disease

Over one million people in the US and six million people worldwide suffer from
Parkinson’s disease, a neurodegenerative disorder caused by the diminished
production of dopamine, resulting in progressive impairment of motor function
including tremors, rigidity, and difficulty in moving. Even when treated with
the current standard of care, the majority of Parkinson’s patients continue to
experience motor fluctuations. These unpredictable OFF episodes reduce
patients’ ability to lead productive, independent lives and are recognized by
patients, care givers, and healthcare professionals as one of the most
troubling and debilitating issues associated with the disease.

About ARCUS^(TM) Platform

The ARCUS^(TM) inhalation technology delivers a reliable and consistent drug
dose with a compact, breath actuated inhaler. The ARCUS^(TM) platform uses a
proprietary dry powder and inhaler combination that is unique in its ability
to deliver a large, precise dose independent of inspiratory flow rate from a
simple, easy-to-use device suitable for convenient self-administration. The
platform has successfully delivered more than one million doses to patients
incorporating active agents ranging from small molecules to large proteins and
has been scaled up to accommodate a commercial product launch.

About Civitas Therapeutics

Civitas is a privately-held pharmaceutical company focused on developing a
robust pipeline of inhaled therapeutics with the clinically proven ARCUS^(TM)
dry powder pulmonary delivery platform. Additional programs encompass
respiratory disease, central nervous system disorders, and infectious disease.
Civitas exclusively licensed and purchased the technology and assets
underlying the ARCUS^(TM) platform from Alkermes plc, including a large
intellectual property estate, a set of development stage pipeline assets,
specialized equipment for respiratory products, and the commercial scale GMP
manufacturing facility. Civitas was launched at the beginning of 2011 with
Canaan Partners, Fountain Healthcare Partners, Longitude Capital, and Alkermes
as investors.

Contact:

Civitas Therapeutics
Stephanie Gillis, 617-660-4110
sgillis@civitastherapeutics.com
 
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