scholarly journals Valuation and Returns of Drug Development Companies: Lessons for Bioentrepreneurs and Investors

2022 ◽  
Author(s):  
Daniel Tobias Michaeli ◽  
Hasan Basri Yagmur ◽  
Timur Achmadeev ◽  
Thomas Michaeli
Keyword(s):  
Drug Development ◽  
Financial Risk ◽  
Real Option ◽  
Phase 1 ◽  
Development Stage ◽  
Success Rates ◽  
Fda Approval ◽  
The Us ◽  
Status Number ◽  
Real Option Value

Abstract Objectives This study evaluates the association of Biopharma company valuation with the lead drug’s development stage, orphan status, number of indications, and disease area. We also estimated annual returns Bioentrepreneurs and investors can expect from founding and investing in drug development ventures. Methods SDC Thomson Reuter and S&P Capital IQ were screened for majority acquisitions of US and EU Biopharma companies developing new molecular entities for prescription use (SIC code: 2834). Acquisition data were complemented with drug characteristics extracted from clinicaltrials.gov, the US Food and Drug Administration (FDA), and deal announcements. Thereafter, company valuations were combined with previously published clinical development periods alongside orphan-, indication-, and disease-specific success rates to estimate annual returns for investments in drug developing companies. Results Based on a sample of 311 Biopharma acquisitions from 2005 to 2020, companies developing orphan, multi-indication, and oncology drugs were valued significantly higher than their peers during later development stages (p < 0.05). We also estimated significantly higher returns for shareholders of companies with orphan relative to non-orphan-designated lead drugs from Phase 1 to FDA approval (46% vs. 12%, p < 0.001). Drugs developed across multiple indications also provided higher returns than single-indication agents from Pre-Clinic to FDA approval (21% vs. 11%, p < 0.001). Returns for oncology drugs exceeded other disease areas (26% vs. 8%, p < 0.001). Conclusions Clinical and economic conditions surrounding orphan-designated drugs translate to a favorable financial risk-return profile for Bioentrepreneurs and investors. Bioentrepreneurs must be aware of the upside real option value their multi-indication drug could offer when negotiating acquisition or licensing agreements.

scholarly journals Workshop Report

2019 ◽  
Vol 125 (9) ◽  
pp. 855-867 ◽  
Author(s):  
Li Pang ◽  
Philip Sager ◽  
Xi Yang ◽  
Hong Shi ◽  
Frederick Sannajust ◽  
...  
Keyword(s):  
Drug Development ◽  
Safety Data ◽  
Development Program ◽  
Initial Step ◽  
White Paper ◽  
Development Stage ◽  
Cardiovascular Safety ◽  
The Us ◽  
Barriers And Challenges ◽  
Structural Injury

Given that cardiovascular safety concerns remain the leading cause of drug attrition at the preclinical drug development stage, the National Center for Toxicological Research of the US Food and Drug Administration hosted a workshop to discuss current gaps and challenges in translating preclinical cardiovascular safety data to humans. This white paper summarizes the topics presented by speakers from academia, industry, and government intended to address the theme of improving cardiotoxicity assessment in drug development. The main conclusion is that to reduce cardiovascular safety liabilities of new therapeutic agents, there is an urgent need to integrate human-relevant platforms/approaches into drug development. Potential regulatory applications of human-derived cardiomyocytes and future directions in employing human-relevant platforms to fill the gaps and overcome barriers and challenges in preclinical cardiovascular safety assessment were discussed. This paper is intended to serve as an initial step in a public-private collaborative development program for human-relevant cardiotoxicity tools, particularly for cardiotoxicities characterized by contractile dysfunction or structural injury.

Analysis of the success rates of new drug development in Japan and the lag behind the US

Health Policy ◽  
2012 ◽  
Vol 104 (3) ◽  
pp. 241-246 ◽  
Author(s):  
Yuka Hirai ◽  
Yosuke Yamanaka ◽  
Makiko Kusama ◽  
Taro Ishibashi ◽  
Yuichi Sugiyama ◽  
...  
Keyword(s):  
Drug Development ◽  
Success Rates ◽  
New Drug ◽  
The Us ◽  
New Drug Development

scholarly journals Fedratinib in myelofibrosis

2020 ◽  
Vol 4 (8) ◽  
pp. 1792-1800 ◽  
Author(s):  
Ann Mullally ◽  
John Hood ◽  
Claire Harrison ◽  
Ruben Mesa
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Phase 1 ◽  
Clinical Development ◽  
Jak2 Inhibitor ◽  
Phase 2 Trial ◽  
Fda Approval ◽  
The Us ◽  
Clinical Hold ◽  
Treatment Naïve ◽  
Poor Nutrition

Abstract Following the discovery of the JAK2V617F mutation in myeloproliferative neoplasms in 2005, fedratinib was developed as a small molecular inhibitor of JAK2. It was optimized to yield low-nanomolar activity against JAK2 (50% inhibitory concentration = 3 nM) and was identified to be selective for JAK2 relative to other JAK family members (eg, JAK1, JAK3, and TYK2). It quickly moved into clinical development with a phase 1 clinical trial opening in 2008, where a favorable impact on spleen and myelofibrosis (MF) symptom responses was reported. A phase 3 trial in JAK2 inhibitor treatment-naive MF patients followed in 2011 (JAKARTA); a phase 2 trial in MF patients resistant or intolerant to ruxolitinib followed in 2012 (JAKARTA-2). Clinical development suffered a major setback between 2013 and 2017 when the US Food and Drug Administration (FDA) placed fedratinib on clinical hold due to the development of symptoms concerning for Wernicke encephalopathy (WE) in 8 of 608 subjects (1.3%) who had received the drug. It was ultimately concluded that there was no evidence that fedratinib directly induces WE, but clear risk factors (eg, poor nutrition, uncontrolled gastrointestinal toxicity) were identified. In August 2019, the FDA approved fedratinib for the treatment of adults with intermediate-2 or high-risk MF. Notably, approval includes a “black box warning” on the risk of serious and fatal encephalopathy, including WE. FDA approval was granted on the basis of the JAKARTA studies in which the primary end points (ie, spleen and MF symptom responses) were met in ∼35% to 40% of patients (JAKARTA) and 25% to 30% of patients (JAKARTA-2), respectively.

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.

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?

Enrollment disparities in cancer clinical trials leading to FDA approvals between 2008 and 2020.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18501-e18501
Author(s):  
Ryan Huu-Tuan Nguyen ◽  
Yomaira Silva ◽  
Vijayakrishna K. Gadi
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Clinical Trials ◽  
Drug Approval ◽  
The United States ◽  
Cancer Clinical Trials ◽  
Cancer Prevalence ◽  
Fda Approval ◽  
The Us ◽  
Enrollment Data

e18501 Background: Cancer clinical trials based in the United States (US) have lacked adequate representation of racial and ethnic minorities, the elderly, and women. Pivotal clinical trials leading to United States Food and Drug Administration (FDA) approval are often multi-national trials and may also lack generalizability to underrepresented populations in the United States. We determined the racial, ethnic, age, and sex enrollment in pivotal trials relative to the US cancer population. Methods: We reviewed the FDA’s Drug Approvals and Databases for novel and new use drug approvals for breast, colorectal, lung, and prostate cancer indications from 2008 through 2020. Drugs@FDA was searched for drug approval summaries and FDA labels to identify clinical trials used to justify clinical efficacy that led to FDA approval. For eligible trials, enrollment data were obtained from FDA approval summaries, FDA labels, ClinicalTrials.gov, and corresponding journal manuscripts. Enrollment Fraction (EF) was calculated as enrollment in identified clinical trials divided by 2017 SEER cancer prevalence. All data sources were publicly available. Results: From 2008 through 2020, 60 drugs received novel or new use drug approval for breast, colorectal, lung, or prostate cancer indications based on 66 clinical trials with a total enrollment of 36,830. North America accounted for 9,259 (31%) enrollees of the 73% of trials reporting location of enrollment. Racial demographics were reported in 78% of manuscripts, 66% of ClinicalTrials.gov pages, and 98% of FDA labels or approval summaries. Compared with a 0.4% enrollment fraction among White patients, lower enrollment fractions were noted in Hispanic (0.2%, odds ratio [OR] vs White, 0.46; 95% confidence interval [CI], 0.43 to 0.49, P< 0.001) and Black (0.1%, OR 0.29; 95% CI 0.28 to 0.31, P< 0.001) patients. Elderly patients (age ≥ 65 years) were less likely than younger patients to be enrollees (EF 0.3% vs 0.9%, OR 0.27; 95% CI 0.26 to 0.27, P< 0.001) despite accounting for 61.3% of cancer prevalence. For colorectal and lung cancer trials, females were less likely than males (EF 0.7% vs 1.1%, OR 0.66; 95% CI 0.63 to 0.68, P< 0.001) to be enrolled. Conclusions: Black, Hispanic, elderly, and female patients were less likely to enroll in cancer clinical trials leading to FDA approvals from 2008 to 2020. Race and geographic enrollment data were inconsistently reported in journal manuscripts and ClinicalTrials.gov. The lack of appropriate representation of specific patient populations in these key clinical trials limits their generalizability. Future efforts must be made to ensure equitable access, representation, and reporting of enrollees that adequately represent the US population of patients with cancer.

Luspatercept in the treatment of lower-risk myelodysplastic syndromes

2021 ◽  
Author(s):  
Onyee Chan ◽  
Rami S Komrokji
Keyword(s):  
Clinical Trials ◽  
Myelodysplastic Syndromes ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Safety Data ◽  
Erythroid Differentiation ◽  
Fda Approval ◽  
The Us ◽  
Us Fda ◽  
Terminal Erythroid Differentiation

Transforming growth factor beta (TGF-β) signaling pathway is key to hematopoiesis regulation. Increased activation of this pathway contributes to ineffective terminal erythroid differentiation in myelodysplastic syndromes (MDS). Luspatercept is a novel fusion protein that traps TGF-β ligands preventing them from binding to Type II TGF-β receptors, thereby decreasing phosphorylated SMAD2/3 resulting in the downstream effect of promoting erythropoiesis. Seminal clinical trials using luspatercept, PACE-MD and MEDALIST, demonstrated impressive efficacy in the treatment of transfusion-dependent anemia in intermediate risk or lower MDS had led to the US FDA approval for this indication. This review summarizes luspatercept mechanisms of action, efficacy/safety data supporting its use and ongoing clinical trials in MDS.

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