scholarly journals Parkinson’s Disease Drug Development Since 1999: A Story of Repurposing and Relative Success

2021 ◽  
pp. 1-9
Author(s):  
Deirdre M. Boucherie ◽  
Gonçalo S. Duarte ◽  
Tiago Machado ◽  
Patrícia R. Faustino ◽  
Cristina Sampaio ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Development ◽  
Success Rate ◽  
Phase 1 ◽  
Phase 2 ◽  
Development Programs ◽  
Inclusion Criteria ◽  
Phase 3 ◽  
Heterogeneous Nature

Background: A global overview of drug development programs in Parkinson’s disease over the last few decades is lacking, while such programs are challenging given the multifaceted and heterogeneous nature of the disease. Objective: To indirectly assess drug development programs in Parkinson’s disease, exploring some factors associated with compound attrition at different trial phases. Methods: We assessed all Parkinson’s disease trials in the WHO trials portal, from inception (1999) to September 2019. Independent authors selected trials and extracted data. The success rate was the number of compounds that progressed to the next drug development phase divided by the number of compounds in that phase. Results: Overall, 357 trials (studying 152 compounds) fulfilled our inclusion criteria, with 62 (17.3%) phase 1 trials, 135 (37.8%) phase 2 trials, 85 (23.8%) phase 3 trials, and 53 (14.8%) phase 4 trials. The success rate was 42.4% from phase 2 to 3. Original compounds received regulatory approval by the FDA in 21.4% of cases, compared with 6.7% of repurposed compounds, representing an overall success rate of 14.9%. We found 172 trials (48.2%) conducted for repurposing previously licensed compounds. These figures were approximately the same regarding approval by the EMA. Most compounds were approved to treat parkinsonism and motor fluctuations. Conclusion: We found a moderate-to-high success rate in all phases of drug development. This was largely based on the success of original compounds, despite almost half of the identified trials attempting compound repurposing.

Clinical Drug Development for the Treatment of Pulmonary Arterial Hypertension: Collaboration With the Pharmaceutical Industry and Regulatory Agencies

2010 ◽  
Vol 9 (4) ◽  
pp. 214-219
Author(s):  
Robyn J. Barst
Keyword(s):  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Drug Development ◽  
Phase 1 ◽  
Preclinical Studies ◽  
Phase 2 ◽  
Phase 3 ◽  
Preclinical Testing ◽  
New Drug ◽  
Pulmonary Arterial

Drug development is the entire process of introducing a new drug to the market. It involves drug discovery, screening, preclinical testing, an Investigational New Drug (IND) application in the US or a Clinical Trial Application (CTA) in the EU, phase 1–3 clinical trials, a New Drug Application (NDA), Food and Drug Administration (FDA) review and approval, and postapproval studies required for continuing safety evaluation. Preclinical testing assesses safety and biologic activity, phase 1 determines safety and dosage, phase 2 evaluates efficacy and side effects, and phase 3 confirms efficacy and monitors adverse effects in a larger number of patients. Postapproval studies provide additional postmarketing data. On average, it takes 15 years from preclinical studies to regulatory approval by the FDA: about 3.5–6.5 years for preclinical, 1–1.5 years for phase 1, 2 years for phase 2, 3–3.5 years for phase 3, and 1.5–2.5 years for filing the NDA and completing the FDA review process. Of approximately 5000 compounds evaluated in preclinical studies, about 5 compounds enter clinical trials, and 1 compound is approved (Tufts Center for the Study of Drug Development, 2011). Most drug development programs include approximately 35–40 phase 1 studies, 15 phase 2 studies, and 3–5 pivotal trials with more than 5000 patients enrolled. Thus, to produce safe and effective drugs in a regulated environment is a highly complex process. Against this backdrop, what is the best way to develop drugs for pulmonary arterial hypertension (PAH), an orphan disease often rapidly fatal within several years of diagnosis and in which spontaneous regression does not occur?

scholarly journals An update on targeted therapies in systemic sclerosis based on a systematic review from the last 3 years

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Corrado Campochiaro ◽  
Yannick Allanore
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Systemic Sclerosis ◽  
Targeted Therapies ◽  
Observational Studies ◽  
Phase 1 ◽  
Phase 2 ◽  
Inclusion Criteria ◽  
Phase 3 ◽  
Trial Drug

AbstractNew molecular mechanisms that can be targeted with specific drugs have recently emerged for the treatment of systemic sclerosis (SSc) patients. Over the past 3 years, the achievement of one large phase 3 trial has led to the approval by drug agencies of the first drug licenced for SSc-related interstitial lung disease. Given this exciting time in the SSc field, we aimed to perform a systemic literature review of phase 1, phase 2 and phase 3 clinical trials and large observational studies about targeted therapies in SSc. We searched MEDLINE/PubMed, EMBASE, and ClinicalTrials.gov for clinical studies from 2016 with targeted therapies as the primary treatment in patients with SSc for skin or lung involvement as the primary clinical outcome measure. Details on the study characteristics, the trial drug used, the molecular target engaged by the trial drug, the inclusion criteria of the study, the treatment dose, the possibility of concomitant immunosuppression, the endpoints of the study, the duration of the study and the results obtained were reviewed. Of the 973 references identified, 21 (4 conference abstracts and 17 articles) were included in the systematic review. A total of 15 phase 1/phase 2 clinical trials, 2 phase 3 clinical trials and 2 observation studies were analysed. The drugs studied in phase 1/phase 2 studies included the following: inebilizumab, dabigatran, C-82, pomalidomide, rilonacept, romilkimab, tocilizumab, tofacitinib, pirfenidone, lenabasum, abatacept, belimumab, riociguat, SAR100842 and lanifibranor. All but 3 studies were performed in early diffuse SSc patients with different inclusion criteria, while 3 studies were performed in SSc patients with interstitial lung disease (ILD). Phase 3 clinical trials investigated nintedanib and tocilizumab. Nintedanib was investigated in SSc-ILD patients whereas tocilizumab focused on early diffuse SSc patients with inflammatory features. Two observational studies including > 50 patients with rituximab as the targeted drug were also evaluated. All these studies offer a real hope for SSc patients. The future challenges will be to customize patient-specific therapeutics with the goal to develop precision medicine for SSc.

scholarly journals P518 Ulcerative colitis drug development success rates are higher than the industry average

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S448-S449
Author(s):  
G Georgiev ◽  
F Hussain ◽  
M Copeman ◽  
M Delegge ◽  
M B Gallagher ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Drug Development ◽  
Phase I ◽  
Success Rate ◽  
Phase Iii ◽  
Molecular Entity ◽  
Phase 2 ◽  
Success Rates ◽  
Phase 3 ◽  
Industry Success

Abstract Background Given the increasing costs of drug development, coupled with low success rates, there is a need to both develop better predictive models and elucidate causes of failure. However, for indications such as ulcerative colitis, a baseline does not presently exist. In this paper, we review trends in drug development and establish a baseline for ulcerative colitis. Methods We used BiomedTracker to obtain information about the number of compounds, which were in development for ulcerative colitis between 2005 and 2018. We counted the number of compounds, which had reached a particular phase, had been discontinued during this phase, had successfully passed it or had been still in this phase. Success rates were derived for the different phases of drug development for all 73 candidate drugs and divided by type of molecule and type of company. A success rate was calculated by dividing the number of drugs successfully completing a particular phase by the sum of the number of drugs which were discontinued during this phase and the number of compounds that completed positively a phase. The likelihood for approval (LOA) for each phase was calculated by multiplying the success rate for the respective phase with the success rates of next stages of development. Results The success rate in phase I was 96 %, in phase II 53 % and in phase III 76%, while the respective LOA was 0.39, 0.4 and 0.76. Table 1 demonstrates the success rates and LOA by type of compound(New molecular entity (NME), Biologic, non-NME) and type of company (big, mid-size, emerging). Conclusion The general industry success rates and LOA for phase I is 64%, for Phase 2 30%, and for phase 3 60% while the LOA from phase I is 10%. These data are published by Michael Hay and co-authors in Nature in January 2014. The success rates in UC drug development are therefore higher than the overall industry success rates.

FUTILITY ANALYSES IN ALZHEIMER’S DISEASE (AD) CLINICAL TRIALS: A RISKY BUSINESS

2020 ◽  
pp. 1-2
Author(s):  
P.S. Aisen ◽  
R. Raman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Development ◽  
Financial Risk ◽  
Phase 1 ◽  
Symptomatic Improvement ◽  
Sufficient Evidence ◽  
Phase 2 ◽  
Financial Loss ◽  
Phase 3

In the standard, orderly progression of drug development trials, a moderately-sized Phase 2 trial demonstrates safety and efficacy of one or more doses of the investigational product, followed by large confirmatory Phase 3 trials of one or two doses leading to regulatory approval. The large and lengthy Phase 3 trials often include interim futility analyses using statistical methods to assess lack of benefit, so that programs “fail early” by identifying ineffective treatments early if evidence points toward lack of efficacy, in part to limit financial loss and redirect resources. For disease-modifying drug development programs in Alzheimer’s disease (AD), finding an optimal strategy is particularly challenging. A slowing of decline rather than symptomatic improvement indicates disease-modification, and primary outcomes for such trials are noisy and sometimes subjective. As a result, very large, lengthy trials are required to see efficacy signals, so Phase 2 trials may look like Phase 3 programs or Phase 3 trials may directly follow Phase 1 trials. In other words, enormous trials may be launched without sufficient evidence of preliminary efficacy of the doses studied, dramatically increasing the financial risk to sponsors. In such instances, futility analyses embedded in trials would seem to be particularly important.

PENERAPAN MODEL QUANTUM LEARNING UNTUK MENINGKATKAN HASIL BELAJAR AUTOCAD SISWA KELAS X TEKNIK PEMESINAN SMK NEGERI 1 STABAT

2013 ◽  
Vol 5 (1) ◽  
Author(s):  
Abdul Hasan Saragih
Keyword(s):  
Positive Response ◽  
Phase 1 ◽  
First Grade ◽  
Learning Model ◽  
Second Phase ◽  
Phase 2 ◽  
Phase 3 ◽  
The Third ◽  
Third Phase ◽  
Quantum Learning

This classroom research was conducted on the autocad instructions to the first grade of mechinary class of SMK Negeri 1 Stabat aiming at : (1) improving the student’ archievementon autocad instructional to the student of mechinary architecture class of SMK Negeri 1 Stabat, (2) applying Quantum Learning Model to the students of mechinary class of SMK Negeri 1 Stabat, arising the positive response to autocad subject by applying Quantum Learning Model of the students of mechinary class of SMK Negeri 1 Stabat. The result shows that (1) by applying quantum learning model, the students’ achievement improves significantly. The improvement ofthe achievement of the 34 students is very satisfactory; on the first phase, 27 students passed (70.59%), 10 students failed (29.41%). On the second phase 27 students (79.41%) passed and 7 students (20.59%) failed. On the third phase 30 students (88.24%) passed and 4 students (11.76%) failed. The application of quantum learning model in SMK Negeri 1 Stabat proved satisfying. This was visible from the activeness of the students from phase 1 to 3. The activeness average of the students was 74.31% on phase 1,81.35% on phase 2, and 83.63% on phase 3. (3) The application of the quantum learning model on teaching autocad was very positively welcome by the students of mechinary class of SMK Negeri 1 Stabat. On phase 1 the improvement was 81.53% . It improved to 86.15% on phase 3. Therefore, The improvement ofstudent’ response can be categorized good.

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