Acorda Therapeutics Research Articles

Subgroup Analyses of Effect of Treatment With Levodopa Inhalation Powder (CVT-301) 84mg by Severity of OFF Symptoms in People with Parkinson’s Disease, as Assessed by the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) (P8-11.017)

<h3>Objective:</h3> An analysis of the proportion of patients who turned ON after CVT-301 84mg treatment vs placebo, compared across patient subgroups with different baseline UPDRS-III scores when experiencing an OFF period in the Phase 3 SPAN-PD study. <h3>Background:</h3> SPAN-PD was an efficacy and safety study of CVT-301 in patients on a stable levodopa/dopa-decarboxylase inhibitor regimen experiencing ≥2h daily OFF periods. Patients were randomized to placebo/CVT-301 for OFF symptom treatment as needed ≤5 times/day. CVT-301 84mg significantly improved motor function at week 12, 30 min post-dose, as measured by lower UPDRS-III scores, with improvement recorded as early as 10 min post-dose. Proportion of patients achieving an ON state at week 12 also demonstrated significant superiority of CVT-301 over placebo (58% of CVT-301 84mg patients turned ON and remained ON at 60 min post-dose, vs 36% of placebo). <h3>Design/Methods:</h3> Analysis compared patients stratified by examiner-rated OFF UPDRS-III score at screening (median UPDRS-III score ≤33 “low” (range 8–33) vs &gt;33 “high” (range 34–75). Treatment differences were calculated between CVT-301 84mg and placebo for the proportion of patients who turned ON and remained ON at 60 min post-dose at week 12 (stratified by Hoehn &amp; Yahr stage, and screening spirometry). <h3>Results:</h3> In the low UPDRS-III group (≤33, n=104) at week 12, 30 (50.0%) CVT-301 patients turned ON post-dose and remained ON at 60 min compared with 11 (25.0%) placebo patients (odds ratio [OR] 3.0, <i>P</i>=0.011). In the high UPDRS group (&gt;33, n=90) at week 12, 26 (70.3%) CVT-301 patients turned ON post-dose vs 24 (45.3%) on placebo (OR 2.8, <i>P</i>=0.026). <h3>Conclusions:</h3> In SPAN-PD , CVT-301 84mg was significantly more effective than placebo in turning patients ON at week 12 in both subpopulations of PD patients experiencing, respectively, more or less severe OFF periods at screening. No substantive difference in drug response was observed between the more and less severe groups. <b>Disclosure:</b> Dr. Cohen has received personal compensation for serving as an employee of Acorda Therapeutics. Dr. Cohen has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for VBL Therapeutics. Dr. Cohen has stock in Acorda Therapeutics. Ping Zhao has received personal compensation for serving as an employee of Acorda Therapeutics Inc. Ping Zhao has received stock or an ownership interest from Acorda Therapeutics Inc.. Richard Marini has received personal compensation for serving as an employee of Acorda Therapeutics. Richard Marini has stock in Acorda Therapeutics. Burkhard Blank has received personal compensation for serving as an employee of Acorda Therapeutics. Burkhard Blank has received stock or an ownership interest from Acorda Therapeutics, Inc. Donald Grosset has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Glasgow Memory Clinic. Donald Grosset has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for IQVIA. Donald Grosset has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for AbbVie. Donald Grosset has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Britannia. Donald Grosset has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GE Healthcare. The institution of Donald Grosset has received research support from Parkinson’s UK. Donald Grosset has received personal compensation in the range of $10,000-$49,999 for serving as a Clinical Director Excellence Network with Parkinson’s UK.

A Prospective Natural History Study of Patients with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) (S49.008)

A Prospective Natural History Study of Patients with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) (S49.008)

P2B001 (low dose combination of extended-release pramipexole and rasagiline) versus titrated extended-release pramipexole in the management of early Parkinson’s disease: Exploratory findings from a randomized, controlled trial (S32.010)

<h3>Objective:</h3> Evaluate the efficacy and safety of P2B001 compared with Extended-Release pramipexole (Prami-ER) in untreated Parkinson’s disease (PD). <h3>Background:</h3> P2B001 is an investigational, fixed low-dose, once-daily combination of ER formulations of pramipexole and rasagiline (0.6/0.75mg). We have previously reported that P2B001 provided significantly superior symptomatic efficacy compared to each of its components (primary efficacy endpoint). Here we report exploratory findings of P2B001 versus Prami-ER which was titrated for optimal efficacy and tolerability. <h3>Design/Methods:</h3> This was an international, multicenter, randomized, double-blind, parallel-group study in patients with early untreated PD comparing once-daily P2B001 to its individual components and to optimally titrated Prami-ER (mean dose of 3.2mg). Eligible patients were aged 35–80y, &lt;3 years from PD diagnosis, and not receiving anti-parkinsonian therapy. Exploratory endpoints are presented along with nominal p-values. <h3>Results:</h3> Changes from baseline to week 12 in total UPDRS (Part II+III) scores between P2B001 and Prami-ER were not significantly different (−8.35 ±0.86 vs 7.98 ±0.6); <i>post-hoc</i> analysis confirmed non-inferiority of P2B001 to Prami-ER (margin of 3 points, p=0.0052). Likewise, there were no significant differences between P2B001 and Prami-ER on UPDRS Part II (activities of daily living) or Part III (motor) scores. Overall, 74.1% of patients receiving P2B001 and 76.6% of patients receiving Prami-ER showed ≥4-point improvement in UPDRS Total scores (Odds ratio 0.87 [0.44, 1.75]; p=0.70). Overall, 74.7% of patients experienced ≥1 TEAE with P2B001 versus 86.5% with titrated Prami-ER and there was a lower frequency of dopaminergic-related TEAEs (44.7% versus 66.2%, respectively). Rates of somnolence (14.7% versus 31.1%) and orthostatic hypotension (2.7% versus 12.2%) were also lower with P2B001 compared with Prami-ER. <h3>Conclusions:</h3> These data indicate that P2B001 offers a once daily treatment option (without the need for titration) for patients with early PD with comparable efficacy to marketed Prami-ER but with reduced sleep-related and dopaminergic side effects. <b>Disclosure:</b> Dr. Elmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Acadia Pharmaceuticals. Dr. Elmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Acorda Therapeutics. Dr. Elmer has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amneal Pharmaceuticals. Dr. Elmer has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva Pharmaceuticals. The institution of Dr. Elmer has received research support from Vaccinex, Inc.. The institution of Dr. Elmer has received research support from Cynapsus Therapeutics, Inc.. The institution of Dr. Elmer has received research support from Lundbeck Pharmaceuticals, Inc.. The institution of Dr. Elmer has received research support from Intec Pharmaceuticals, Inc.. The institution of Dr. Elmer has received research support from Pharma Two B. The institution of Dr. Elmer has received research support from Acadia Pharmaceuticals, Inc.. The institution of Dr. Elmer has received research support from Impax Laboratories, LLC. The institution of Dr. Elmer has received research support from Prilenia Therapeutics. The institution of Dr. Elmer has received research support from Neuraly, Inc.. Dr. Litman has received personal compensation for serving as an employee of PHARMA 2B. Mrs. Friedman has received personal compensation for serving as an employee of Pharma Two B. Dr. Fitzer-Attas has received personal compensation for serving as an employee of Mitsubishi Tanabe Pharma America. The institution of Dr. Fitzer-Attas has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Cyclerion. The institution of Dr. Fitzer-Attas has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Pharma Two B. The institution of Dr. Fitzer-Attas has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Golden Heart Flower. The institution of Dr. Fitzer-Attas has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for B-Portal Biologics. Dr. Fitzer-Attas has stock in Golden Heart Flower. Sheila Oren, MD, MBA has received personal compensation for serving as an employee of Neuroderm. Sheila Oren, MD, MBA has received personal compensation in the range of $0-$499 for serving as a Consultant for Neuroderm.

Integrated safety summary from Phase 3 clinical trials of IPX203, an extended-release carbidopa-levodopa formulation, in Parkinson disease (P1-11.006)

Integrated safety summary from Phase 3 clinical trials of IPX203, an extended-release carbidopa-levodopa formulation, in Parkinson disease (P1-11.006)

A Phase 2 Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous ANX005 in Patients with, or at Risk of, Manifest Huntington’s Disease (HD) (S32.009)

A Phase 2 Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous ANX005 in Patients with, or at Risk of, Manifest Huntington’s Disease (HD) (S32.009)

Efficacy and Safety of DaxibotulinumtoxinA for Injection Over Successive Treatments in Adults With Cervical Dystonia in the Phase 3 ASPEN-1 and ASPEN-OLS Trials (P11-11.006)

Efficacy and Safety of DaxibotulinumtoxinA for Injection Over Successive Treatments in Adults With Cervical Dystonia in the Phase 3 ASPEN-1 and ASPEN-OLS Trials (P11-11.006)

Midclerkship Feedback Quality Improvement via Introduction of Simple Form (P3-2.004)

<h3>Objective:</h3> The provision of formative midpoint feedback in clerkships is required under Accreditation Standard 9.7 of the Liaison Committe on Medical Education (LCME). Our institution uses an end of clerkship evaluation by the medical students to evaluate education program quality (LCME Standard 8.5). The Clerkship Director aimed to improve the perceived quality of mid-clerkship feedback by introducing a form to prompt students to undergo specific discussion of strengths and weaknesses at the end of the first week of the clerkship. <h3>Background:</h3> The Neurology Clerkship at New York Medical College is a four-week required third year medical school clerkship with 4 clinical sites. The largest clinical site is Westchester Medical Center (WMC) with typical enrollment of 10 students per month. <h3>Design/Methods:</h3> Students scored the quality of mid-clerkship feedback on a Likert scale from 1–5, with 5 being best, during their end of clerkship evaluation. Starting in Block 8 (February 2022), a mid-clerkship preparation form was given to students which asked students to solicit individualized feedback from their resident and attending physician preceptors. Students were prompted to list two strengths and two areas to work on. They brought the paper to the formal mid-clerkship feedback session with the Site Director during week 2. <h3>Results:</h3> The average score on the Likert scale for mid-clerkship feedback quality was 3.58 in the 3 blocks preceding the change and 3.71 in the 3 blocks following the change. <h3>Conclusions:</h3> Structured interview tools can improve mid-clerkship feedback experience. <b>Disclosure:</b> Dr. Fekete has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurocrine Biosciences, Inc.. Dr. Fekete has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acorda, Inc.. Dr. Fekete has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Fekete has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva Neuroscience, Inc.. Dr. Fekete has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acadia Pharmaceutical, Inc.. Dr. Fekete has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kirin, Inc.. Dr. Fekete has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Adamas Pharmaceutical, Inc.. Dr. Fekete has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Neurocrine Biosciences, Inc.. Dr. Fekete has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amneal Pharmaceuticals, Inc.. Dr. Fekete has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Acorda Therapeutics, Inc.. Dr. Fekete has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sunovion, Inc.. Dr. Fekete has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medlink, Inc.. The institution of Dr. Fekete has received research support from Lundbeck. Dr. Fekete has received publishing royalties from a publication relating to health care. Dr. Fekete has a non-compensated relationship as a Neurological Working Group Member with Alliance for Patient Access that is relevant to AAN interests or activities.

Continuous, Subcutaneous Apomorphine Infusion for Persistent Motor Fluctuations in Parkinson’s Disease: Full results of the AP2-3000 open-label study (S32.008)

Continuous, Subcutaneous Apomorphine Infusion for Persistent Motor Fluctuations in Parkinson’s Disease: Full results of the AP2-3000 open-label study (S32.008)

Pooled Safety Analysis of IncobotulinumtoxinA in the Treatment of Neurological Disorders in Adults (P12-11.007)

<h3>Objective:</h3> To examine the pooled incidence of treatment-emergent adverse events (TEAEs) and immunogenicity by indication in sponsored incobotulinumtoxinA (INCO) clinical trials in adults. <h3>Background:</h3> The safety and efficacy of INCO in adult neurological disorders has been investigated in multiple prospective clinical trials, including several not yet published. A comprehensive assessment combining available data would provide additional insights into INCO safety. <h3>Design/Methods:</h3> TEAEs were identified in the integrated clinical database of Merz-sponsored placebo (PBO)-controlled studies in adults with cervical dystonia (CD), blepharospasm, upper limb (UL) and lower limb (LL) spasticity, sialorrhea and essential tremor of the UL. Overall incidences of TEAEs and the categories of serious TEAEs (SAEs), TEAEs leading to discontinuation, fatal TEAEs, TEAEs of special interest (AESIs; indicating possible toxin spread) and treatment-related (TR) events were determined for INCO and PBO after a single injection cycle and for INCO after multiple cycles; the most frequent TEAEs, TR-TEAEs and TR-AESIs after a single cycle of INCO were summarized. Neutralizing antibody (NAb) testing was performed in most studies. <h3>Results:</h3> After a single cycle, the incidences of overall TEAEs were similar between INCO and PBO in all indications, although between-indication differences were observed. Most TEAEs were mild to moderate in intensity, and only one subject experienced a TR-SAE. Few TEAEs led to discontinuation of INCO; there were no fatal TEAEs in subjects receiving INCO. In general, repeated cycles did not increase the incidences of any TEAE category. TR-TEAEs affecting ≥1% of patients were uncommon in patients with spasticity. TR-AESIs across all indications were most commonly muscular weakness and dry mouth. Few subjects developed NAb; the vast majority of those positive at the end of the study were also positive at baseline. <h3>Conclusions:</h3> Results of this pooled analysis support and extend the favorable safety and tolerability profile of INCO for the treatment of adult neurological disorders. <b>Disclosure:</b> Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acorda Therapeutics. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck LTD. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan Inc. Dr. Comella has received personal compensation in the range of $0-$499 for serving as a Consultant for Merz. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia. Dr. Comella has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Revance. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sunovion. Dr. Comella has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Aeon. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz . Dr. Comella has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ipsen. Dr. Comella has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz Pharmaceutical. Dr. Comella has received publishing royalties from a publication relating to health care. Dr. Comella has received publishing royalties from a publication relating to health care. Michael Hast has received personal compensation for serving as an employee of Merz. Angelika Hanschmann has received personal compensation for serving as an employee of Merz Pharmaceuticals GmbH.

The Synuclein-One Study: Skin Biopsy Detection of Phosphorylated alpha-synuclein for Diagnosis of the Synucleinopathies (S37.004)

The Synuclein-One Study: Skin Biopsy Detection of Phosphorylated alpha-synuclein for Diagnosis of the Synucleinopathies (S37.004)

Long-term Safety and Efficacy of IPX203 in Parkinson’s Disease Patients with Motor Fluctuations: A 9-Month Open-label Extension Trial (S32.006)

Long-term Safety and Efficacy of IPX203 in Parkinson’s Disease Patients with Motor Fluctuations: A 9-Month Open-label Extension Trial (S32.006)

Industry Update, October 2022.

Industry Update, October 2022.

Industry Update: the Latest Developments in the Field of Therapeutic delivery, 1–31 December 2018

1-31 December 2018, the period covered by this article, was again a very interesting period for activity under the therapeutic delivery umbrella, being a particularly solid month for business activity, notably a major acquisition by GSK to expand its oncology portfolio. This was, as it later turns out, the first of several very significant mergers and acquisitions around the turn of the year in the oncology area, more of which will appear in future articles. In that acquisition, the acquisition of Potenza Therapeutics (MA, USA) by Astellas Pharma Inc. (Tokyo, Japan), Amgen's (CA, USA) collaboration with Molecular Partners (Zurich, Switzerland), the partnership between Domain Therapeutics (Strasbourg, France) and Boehringer Ingelheim (Ingelheim am Rhein, Germany), and the deal between Argenx (Breda, The Netherlands) and Cilag GmbH International (Zug, Switzerland), all announced in the month, demonstrated the high continued interest within industry around the development of immuno-oncology therapeutics. Additionally, activity around therapeutic delivery technologies was prominent in the news, for example the Amgen/Entera Bio (Jerusalem, Israel) deal around oral delivery of large molecules, Entrada Therapeutic's (MA, USA) successful acquisition of funding to advance its work on intracellular delivery of biologics, Impel NeuroPharma's (WA, USA) securing of support continue its development of its nose-to-brain delivery pipeline, US FDA approval of inhaled levodopa from Acorda Therapeutics Inc. (NY, USA) and a sublingual delivery technology for dexmedetomidine under development by BioXcel Therapeutics (CT, USA) being advanced into clinical evaluation were just some of the items noted. As always, information sources employed to provide the materials used in compiling this update included company press releases, conference news and other news websites.

Aerosol delivery of dry powder synthetic lung surfactant to surfactant-deficient rabbits and preterm lambs on non-invasive respiratory support.

Background: The development of synthetic lung surfactant for preterm infants has focused on peptide analogues of native surfactant proteins B and C (SP-B and SP-C). Non-invasive respiratory support with nasal continuous positive airway pressure (nCPAP) may benefit from synthetic surfactant for aerosol delivery. Methods: A total of three dry powder (DP) surfactants, consisting of phospholipids and the SP-B analogue Super Mini-B (SMB), and one negative control DP surfactant without SMB, were produced with the Acorda Therapeutics ARCUS® Pulmonary Dry Powder Technology. Structure of the DP surfactants was compared with FTIR spectroscopy, in vitro surface activity with captive bubble surfactometry, and in vivo activity in surfactant-deficient adult rabbits and preterm lambs. In the animal experiments, intratracheal (IT) aerosol delivery was compared with surfactant aerosolization during nCPAP support. Surfactant dosage was 100 mg/kg of lipids and aerosolization was performed using a low flow inhaler. Results: FTIR spectra of the three DP surfactants each showed secondary structures compatible with peptide folding as an α-helix hairpin, similar to that previously noted for surface-active SMB in other lipids. The DP surfactants with SMB demonstrated in vitro surface activity <1 mN/m. Oxygenation and lung function increased quickly after IT aerosolization of DP surfactant in both surfactant-deficient rabbits and preterm lambs, similar to improvements seen with clinical surfactant. The response to nCPAP aerosol delivery of DP surfactant was about 50% of IT aerosol delivery, but could be boosted with a second dose in the preterm lambs. Conclusions: Aerosol delivery of DP synthetic surfactant during non-invasive respiratory support with nCPAP significantly improved oxygenation and lung function in surfactant-deficient animals and this response could be enhanced by giving a second dose. Aerosol delivery of DP synthetic lung surfactant has potential for clinical applications.

Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 trial

Patients with Parkinson's disease chronically treated with levodopa commonly have delayed or unpredictable onset of its benefits after oral intake. In this study, we assessed the safety and efficacy of CVT-301, a self-administered levodopa oral inhalation powder, for the treatment of patients with Parkinson's disease during off periods. In this randomised, double-blind, placebo-controlled, phase 3 trial, patients were recruited at 65 sites in Canada, Poland, Spain, and the USA. Eligible participants were patients with Parkinson's disease aged 30-85 years, who had daily off periods of 2 h or longer and showed an improvement of 25% or greater in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score from off to on state after use of an oral levodopa plus a dopa-decarboxylase inhibitor combination. Patients were assigned (1:1:1) with a computer-generated randomisation code, in fixed blocks of six, to either CVT-301 60 mg, CVT-301 84 mg, or placebo. Spirometry results and modified Hoehn and Yahr disease stage at screening were used for stratification of treatment groups. Patients, the sponsor, and site personnel were masked to treatment assignment. Each study dose consisted of two capsules administered with an inhaler. Patients were instructed to use the study drug as needed for off periods, and could self-administer up to five doses per day. The primary endpoint was the change in UPDRS motor score from predose to 30 min postdose, assessed at week 12 during an in-clinic off period, in the CVT-301 84 mg group compared with the placebo group. Analysis was by intention to treat. Safety was assessed in all patients who received at least one dose of experimental treatment. This trial is registered with ClinicalTrials.gov, number NCT02240030. Between Dec 4, 2014, and Aug 26, 2016, 351 patients were enrolled and randomly assigned to receive CVT-301 60 mg (115 patients), CVT-301 84 mg (120 patients), or placebo (116 patients). Of these, 339 received the assigned study treatment (CVT-301 60 mg, n=113; CVT-301 84 mg, n=114; placebo, n=112) and 290 completed the study (CVT-301 60 mg, n=96; CVT-301 84 mg, n=97; placebo, n=97). The least-squares mean difference in UPDRS motor score change from predose to 30 min postdose was -5·91 (SE 1·50, 95% CI -8·86 to -2·96) for the placebo group and -9·83 (1·51; -12·79 to -6·87) for the CVT-301 84 mg group (between-group difference -3·92 [-6·84 to -1·00]; p=0·0088). Treatments were safe and well tolerated. Severe adverse events were reported by 2 (2%) of 112 patients in the placebo group, 7 (6%) of 113 in the CVT-301 60 mg group, and 5 (4%) of 114 in the CVT-301 84 mg group, with no severe adverse event occurring in more than one patient in any treatment group. 11 (3%) of 339 patients had 19 serious adverse events (three [3%] of 112 patients in placebo, six [5%] of 113 in CVT-301 60 mg, and two [2%] of 114 in CVT-301 84 mg). Of these, hypotension and atrial fibrillation were assessed by investigators to be possibly related to the study drug. CVT-301 can improve UPDRS motor scores of patients with Parkinson's disease during in-clinic off periods, with few severe or serious adverse events. The long-term safety and efficacy of CVT-301 need to be investigated in future studies. Acorda Therapeutics.

Aerosol delivery of dry powder synthetic lung surfactant to surfactant-deficient rabbits and preterm lambs on non-invasive respiratory support

Background: The development of synthetic lung surfactant for preterm infants has focused on peptide analogues of native surfactant proteins B and C (SP-B and SP-C). Non-invasive respiratory support with nasal continuous positive airway pressure (nCPAP) may benefit from synthetic surfactant for aerosol delivery. Methods: A total of three dry powder (DP) surfactants, consisting of phospholipids and the SP-B analogue Super Mini-B (SMB), and one negative control DP surfactant without SMB, were produced with the Acorda Therapeutics ARCUS® Pulmonary Dry Powder Technology. Structure of the DP surfactants was compared with FTIR spectroscopy, in vitro surface activity with captive bubble surfactometry, and in vivo activity in surfactant-deficient adult rabbits and preterm lambs. In the animal experiments, intratracheal (IT) aerosol delivery was compared with surfactant aerosolization during nCPAP support. Surfactant dosage was 100 mg/kg of lipids and aerosolization was performed using a low flow inhaler. Results: FTIR spectra of the three DP surfactants each showed secondary structures compatible with peptide folding as an α-helix hairpin, similar to that previously noted for surface-active SMB in other lipids. The DP surfactants with SMB demonstrated in vitro surface activity &lt;1 mN/m. Oxygenation and lung function increased quickly after IT aerosolization of DP surfactant in both surfactant-deficient rabbits and preterm lambs, similar to improvements seen with clinical surfactant. The response to nCPAP aerosol delivery of DP surfactant was about 50% of IT aerosol delivery, but could be boosted with a second dose in the preterm lambs. Conclusions: Aerosol delivery of active DP synthetic surfactant during non-invasive respiratory support with nCPAP significantly improved oxygenation and lung function in surfactant-deficient animals and this response could be enhanced by giving a second dose. Aerosol delivery of DP synthetic lung surfactant has potential for clinical applications.

Acorda Therapeutics, Inc. v. Roxane Laboratories, Inc. United States Court of Appeals of the Federal Circuit, 2018 903 F.3d 1310

Biotechnology Law ReportVol. 37, No. 6 Case in PointAcorda Therapeutics, Inc. v. Roxane Laboratories, Inc. United States Court of Appeals of the Federal Circuit, 2018 903 F.3d 1310Edited for Biotechnology Law Report by CHRISTOPHER M. HOLMAN*Published Online:10 Dec 2018https://doi.org/10.1089/blr.2018.29093.cmhAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 37Issue 6Dec 2018 InformationCopyright 2018, Mary Ann Liebert, Inc., publishersTo cite this article:Acorda Therapeutics, Inc. v. Roxane Laboratories, Inc. United States Court of Appeals of the Federal Circuit, 2018 903 F.3d 1310.Biotechnology Law Report.Dec 2018.334-351.http://doi.org/10.1089/blr.2018.29093.cmhPublished in Volume: 37 Issue 6: December 10, 2018PDF download

Acorda Therapeutics and the Role of Blocking Patents in Assessing Objective Indicia of Nonobviousness in the Pharmaceutical Arts

<i>Acorda Therapeutics</i> and the Role of Blocking Patents in Assessing Objective Indicia of Nonobviousness in the Pharmaceutical Arts

Factors Associated with Sexual Dysfunction in Individuals with Multiple Sclerosis

Sexual dysfunction is a common symptom of multiple sclerosis (MS) that often goes unreported by both the patient and the clinician. Sexual dysfunction can affect a person's mood, relationships, daily functioning, and quality of life. Gaining a better understanding of the prevalence and nature of sexual dysfunction in individuals with MS would not only help identify patients with this problem but also determine contributing factors, which can inform treatment alternatives available to the patient. Patients with a diagnosis of MS (n = 162) completed the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 during their neurology appointments at the Mellen Center for Multiple Sclerosis at Cleveland Clinic. These data were merged with Knowledge Program data collected as part of standard practice and included measures of mood, disability, and quality of life. Sexual dysfunction was present in 64.2% of the clinic sample. Patients with sexual dysfunction had significantly worse average MS-related disability and depressive symptom scores. Sexual dysfunction is highly prevalent in the MS clinic sample. Assessment and treatment of depression may serve as a starting point for intervention in patients with MS who experience sexual dysfunction. Identifying individuals who are at risk for sexual dysfunction concerns may help with clinician and patient burden in terms of routine assessment of this symptom.

Inpatient Admissions and Costs Associated with Persistent Use of Dalfampridine Extended-Release in Multiple Sclerosis: A Claims Database Analysis.

While the clinical benefits of dalfampridine extended-release (D-ER) have been established in patients with multiple sclerosis (MS) through multiple clinical trials, there is limited real-world data on D-ER use, in particular the persistent use of D-ER, and associated acute care resource utilization and costs. To examine the real-world association of D-ER use and inpatient admissions and costs among patients with MS. This study was a retrospective observational claims analysis of the MarketScan database (April 2009-March 2014). Eligible patients consisted of adult enrollees aged 18-64 years who had (a) 12 months of continuous private plan enrollment preceding (baseline) and following (follow-up) the first D-ER claim; (b) ≥ 2 MS diagnosis codes with ≥ 1 during the baseline period; (c) ≥ 2 consecutive D-ER claims; and (d) no alternate gait-impairing etiologies during the baseline and follow-up periods. Patients were separated into 2 D-ER cohorts in the main analysis: persistent (≥ 360 days of D-ER supply) and nonpersistent (< 360 days of supply) users. Sensitivity analyses were conducted, examining additional breakdowns of days of supply within the nonpersistent cohort. Inpatient admissions (all-cause and MS-related) and health care expenditures were calculated and compared between the cohorts during follow-up using Wilcoxon rank-sum and chi-square tests. Regression models were conducted, controlling for age, sex, MS relapses, comorbidities, disease-modifying therapy use, and other baseline factors, including inpatient admissions and costs. Of 1,598 eligible patients, 719 (45.0%) were persistent D-ER users, and 879 (55.0%) were nonpersistent D-ER users. The 2 cohorts had similar demographic and clinical characteristics, with mean (SD) ages of 51.0 (8.4) and 50.6 (8.6) years and were 71.3% and 66.6% female, respectively. Compared with nonpersistent D-ER use, persistent D-ER use was associated with lower odds of all-cause inpatient admissions (OR = 0.58, P = 0.010) and MS-related inpatient admissions (OR = 0.50, P = 0.004). Persistent use was also associated with lower inpatient expenditures for all-cause admissions ($669 vs. $1,515, P = 0.002) and MS-related admissions ($388 vs. $891, P = 0.008). Persistent D-ER use was associated with significantly lower rates of all-cause and MS-related inpatient admissions and costs. Funding for this research and medical writing assistance was provided by Acorda Therapeutics. The study sponsor was involved in all stages of the study research and manuscript preparation. Guo and Niyazov were employees of Acorda Therapeutics at the time of this study and may own stock/stock options. Wu, Macaulay, Terasawa, and Schmerold are employees of Analysis Group, which received consultancy fees from Acorda Therapeutics for this project. Krieger was a consultant for Acorda Therapeutics for this project and has the following additional financial interests to report: consulting/advisory board work with Bayer, Biogen, EMD Serono, Novartis, Genentech, Genzyme, and Teva. Study concept and design were contributed by Guo, Niyazov, Macaulay, and Wu. Macaulay, Terasawa, Schmerold, and Wu helped prepare the data, and data interpretation was performed by Krieger, Guo, Niyazov, and Macaulay, along with Terasawa and Wu. The manuscript was written by Terasawa and Schmerold, along with Macaulay, and revised by all the authors. A portion of the current research was presented in poster format at the 2106 American Academy of Neurology Annual Meeting, which took place in Vancouver, BC, Canada, on April 15-21, 2016.