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Last update 08 Nov 2025

Midodrine Hydrochloride

Last update 08 Nov 2025

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

SummaryMidodrine, a diminutive molecule of therapeutic nature, exhibits its therapeutic effect through its agonistic action upon the α-adrenergic receptor. This pharmacological agent is commonly utilized to ameliorate hypotension, particularly orthostatic hypotension, via its vasoconstrictive actions that lead to a rise in blood pressure. Midodrine obtained approval from the Food and Drug Administration (FDA) in March of the year 1987, and its development can be attributed to the eminent pharmaceutical company, Shire. As an agonist for the α-adrenergic receptor, Midodrine engenders a robust stimulatory response of the sympathetic nervous system, which in turn orchestrates the regulation of both heart rate and blood pressure. By virtue of its multifarious actions, Midodrine has proven efficacy in addressing various maladies stemming from hypotension, encompassing autonomic dysfunction and chronic fatigue syndrome.

Drug Type

Small molecule drug

Synonyms

(±)-2-amino-N-(β-hydroxy-2,5-dimethoxyphenethyl)acetamide, 1-(2',5'-Dimethoxyphenyl)-2-glycinamidoethanol, 2-Amino-N-(2,5-dimethoxy-beta-hydroxyphenethyl)acetamide

+ [25]

Target

ADRA1

Action

agonists

Mechanism

ADRA1 agonists(Adrenergic receptor alpha-1 agonists)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesOther Diseases

Active Indication

HypotensionHypotension, Orthostatic

Inactive Indication

Fatigue Syndrome, ChronicNeurogenic Orthostatic Hypotension

Originator Organization

Shire Plc

Active Organization

Shire Pharmaceuticals Services Ltd.

Takeda Pharmaceutical Co., Ltd.Southern XP IP Pty Ltd

+ [3]

Inactive Organization

Shire Pharmaceuticals GroupRoberts Pharmaceutical Corp.Takeda Pharmaceuticals U.S.A., Inc.

License Organization-

Drug Highest PhaseApproved

First Approval Date

Japan (29 Jun 1989),

Hypotension, OrthostaticHypotension

RegulationOrphan Drug (United States)

Structure/Sequence

Molecular FormulaC12H19ClN2O4

InChIKeyMGCQZNBCJBRZDT-UHFFFAOYSA-N

CAS Registry43218-56-0

114

Clinical Trials associated with Midodrine Hydrochloride

ChiCTR2500106791

/ Not yet recruitingNot ApplicableIIT

Clinical Study of Midodrine-Based Combination Therapy for CD38 Antibody-Refractory Multiple Myeloma

Start Date01 Aug 2025

Sponsor / Collaborator-

NCT06930235

/ RecruitingNot ApplicableIIT

Effectiveness of Midodrine as an Adjuvant to Norepinephrine in Weaning Critically Ill Patients From Vasopressors

This study aims to evaluate the effectiveness of midodrine as an adjuvant to norepinephrine in weaning critically ill patients from vasopressors

Start Date13 Mar 2025

Sponsor / Collaborator

Sohag University

CTRI/2024/09/074117

/ Not yet recruitingPhase 3IIT

Midodrine and clonidine in patients with cirrhosis and refractory or recurrent ascites : a randomized controlled trial - NIL

Start Date01 Oct 2024

Sponsor / Collaborator-

100 Clinical Results associated with Midodrine Hydrochloride

100 Translational Medicine associated with Midodrine Hydrochloride

100 Patents (Medical) associated with Midodrine Hydrochloride

989

Literatures (Medical) associated with Midodrine Hydrochloride

01 Dec 2025·IMMUNOLOGIC RESEARCH

Dysautonomia: a common comorbidity of systemic disease

Review

Author: Blitshteyn, Svetlana

Abstract:

Referring to a broad spectrum of the autonomic symptoms, autonomic disorders, and general dysfunction of the autonomic nervous system, dysautonomia is one of the common and under-recognized comorbidities of a wide variety of systemic disease, including diabetes, autoimmune disorders, vitamin deficiencies, and hormonal dysregulation. The most common autonomic disorders encountered in clinical practice are postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope (NCS), and orthostatic hypotension (OH), which may be undiagnosed or often mislabeled with psychiatric disorders. Typical clinical features of dysautonomia, such as orthostatic dizziness/lightheadedness, orthostatic intolerance, palpitations, exercise intolerance, cognitive dysfunction, and fatigue, should prompt a diagnostic investigation for dysautonomia, which includes an in-office 10-min stand test or a tilt table test in conjunction with other autonomic function tests if available. Treatment approach consists of non-pharmacologic and pharmacologic therapies with beta blockers, midodrine, ivabradine, pyridostigmine, fludrocortisone, stimulants, and other medications. In clinical setting, dysautonomia may present a diagnostic and therapeutic challenge in patients with various systemic disorders and may require a high index of suspicion on the part of the clinician. Importantly, diagnosing and treating dysautonomia is critical to providing comprehensive and personalized medical care to complex patients with chronic illness, who are typically highly symptomatic with multi-systemic complaints as a result of comorbid, and often undiagnosed, dysautonomia.

10 Oct 2025·Current Hypertension Reviews

Orthostatic Hypotension in Older Adults: A Narrative Review of Causes, Drug Impacts, and Management Strategies

Article

Author: Bhati, Vishal ; Mittal, Payal

Introduction::

Orthostatic hypotension (OH) is a prevalent disorder among the elderly, characterized by a marked decrease in blood pressure upon standing. It impacts 10–30% of elderly individuals and is linked to falls, cognitive deterioration, and cardiovascular issues. The primary factors include aging, autonomic dysfunction, and pharmaceutical usage.

Methods::

This narrative review consolidates and examines contemporary research regarding the etiology, pharmacological effects, diagnosis, and treatment of orthostatic hypotension in elderly adults. A systematic technique was not employed; rather, expert analysis of the existing literature was utilized to distill essential ideas.

Results::

OH in the elderly is frequently complex. Frequently involved drugs encompass diuretics, β-blockers, calcium channel blockers, ACE inhibitors, antidepressants, and antiparkinsonian ther-apies. These medications, within the framework of age-associated physiological alterations, elevate the risk of orthostatic hypotension. The diagnosis relies on monitoring blood pressure during changes in posture. Non-pharmacological interventions, including water, sodium consumption, compression garments, and physical movements, constitute first-line therapies. In chronic in-stances, pharmacological treatments such as midodrine, droxidopa, and fludrocortisone may be employed, albeit with vigilant monitoring due to potential deleterious effects.

Discussion::

OH significantly affects the autonomy and quality of life of elderly individuals. Med-ication-induced orthostatic hypotension is frequently disregarded, particularly in the context of polypharmacy. Customized management, encompassing drug evaluation and integrated therapy approaches, is crucial. Clinical monitoring and regular orthostatic evaluations are essential for prompt diagnosis and management.

Conclusion::

Effective OH management requires a personalized, multidisciplinary approach. Fu-ture research should focus on identifying reliable diagnostic biomarkers and developing individu-alized treatment algorithms to improve patient outcomes and support healthy aging.

03 Oct 2025·CLINICAL TOXICOLOGY

Midodrine exposure trends and outcomes reported to United States poison centers: 2000–2023

Article

Author: Schnall, Amy ; Nogee, Daniel Philip ; Geller, Andrew ; Kieszak, Stephanie ; Yeh, Michael ; Kuai, David

INTRODUCTION:

Midodrine is an oral alpha-1 adrenergic agonist used to treat orthostatic hypotension. Its vasoconstrictive properties can lead to hypertension and reflex bradycardia. We characterized midodrine exposures reported to United States poison centers from 2000 to 2023.

METHODS:

We performed a retrospective analysis of single-substance midodrine exposures reported to the National Poison Data System^®. Descriptive statistics were used to characterize temporal trends, demographics, exposure reasons, level of healthcare, and medical outcomes. National estimates of retail outpatient midodrine prescriptions during 2002-2023 were obtained from IQVIA Total Patient Tracker.

RESULTS:

The number of patients dispensed midodrine from retail pharmacies increased 695%, from 55,300 in 2002 to 439,659 in 2023. There were 1,935 midodrine exposures reported to the National Poison Data System^® from 1 January 2000 to 31 December 2023. Exposures increased 714%, from 21 calls in 2000 to 171 calls in 2023. The most common features reported were hypertension in 277 (14.3%) and bradycardia in 197 (10.2%). Therapeutic errors accounted for most cases in most age groups except adolescents aged 13-19 years, in which suspected suicide was the most commonly reported reason (50.2%). Most exposures were managed at home. Among 866 patients who sought medical care, 437 (50.5%) were treated/evaluated and released, but 115 (13.3%) were admitted to a critical care unit.

DISCUSSION:

Midodrine exposures increased over time, particularly among individuals aged 20-59 years and 60 years and older, with a concomitant increase in retail midodrine dispensing. Although most exposures were managed at home, severe adverse effects have been reported, especially among patients with suspected suicidal ingestions compared to those with therapeutic errors. The National Poison Data System^® is limited by its passive surveillance design, and not all exposures are reported.

CONCLUSIONS:

Better understanding of midodrine exposures and associated outcomes can inform poison center triage and medical management. Improved surveillance and clinician awareness may reduce morbidity and mortality associated with midodrine toxicity.

News (Medical) associated with Midodrine Hydrochloride

21 Dec 2023

·www.prnewswire.com

Mallinckrodt Announces Journal Publication of Economic Evidence for TERLIVAZ® (terlipressin) for Injection in Adults with Hepatorenal Syndrome (HRS)

– Analysis indicates treatment with TERLIVAZ plus albumin in adults with HRS with rapid reduction in kidney function1 can help improve kidney function with lower HRS treatment-related healthcare utilization costs2 – – Journal manuscript with full data results now published in the December issue of Advances in Therapy – DUBLIN, Dec. 21, 2023 /PRNewswire/ -- Mallinckrodt plc, a global specialty pharmaceutical company, recently announced the publication of findings from a cost analysis of TERLIVAZ® (terlipressin) for injection for adults with hepatorenal syndrome (HRS) with rapid reduction in kidney function.1,2 This analysis assessed the treatment-related cost per patient response with TERLIVAZ plus albumin from a U.S. hospital perspective.2 The manuscript was published in the December 2023 print issue of Advances in Therapy and is also available on the Advances in Therapy website. TERLIVAZ is the first and only FDA-approved product indicated to improve kidney function in adults with HRS with rapid reduction in kidney function,1 an acute and life-threatening condition requiring hospitalization.3 HRS involving rapid reduction in kidney function1 is estimated to affect more than 42,000 Americans annually and rates of HRS hospitalizations are increasing.4 Please see Limitation of Use and Important Safety Information, including Boxed Warning, below. The publication, titled "Treatment-Related Cost Analysis of Terlipressin for Adults with Hepatorenal Syndrome with Rapid Reduction in Kidney Function," used a decision analytic model to estimate the treatment-related cost associated with TERLIVAZ plus albumin and other non-FDA approved treatments, such as midodrine and octreotide plus albumin and norepinephrine plus albumin, for adult patients with HRS with rapid reduction in kidney function.1,2 HRS treatment-related utilization of healthcare resources from the U.S. hospital perspective, including the incremental cost of intensive care unit (ICU) bed, dialysis, pulse oximetry monitoring and adverse events, was estimated based on the level of response.2 HRS reversal (or complete response) was defined as a decrease in serum creatinine (SCr) from baseline to ≤ 1.5 mg/dL on treatment (up to 24 hours after the last treatment dose).2 "Continued research on the real-world clinical and economic impact of TERLIVAZ is critical to further our understanding of the relationship between HRS treatment choice and patient outcomes, and the related healthcare costs," said George Wan, Ph.D., M.P.H., Vice President, Evidence Generation & Data Sciences. "These findings suggest that TERLIVAZ may help to improve kidney function with lower ICU, dialysis, and other HRS treatment-related healthcare utilization costs when compared to other non-FDA approved treatments used in the U.S. hospital setting.2" Key Findings2: The cost per response of TERLIVAZ plus albumin was lower than midodrine and octreotide plus albumin ($85,315 vs. $467,794) and norepinephrine plus albumin ($81,614 vs. $139,324). Midodrine and octreotide plus albumin resulted in higher ICU- and dialysis-related costs (ICU: $9,039; dialysis: $8,266) vs. TERLIVAZ plus albumin (ICU: $6,712; dialysis: $5,073). Similarly, norepinephrine plus albumin resulted in higher ICU- and dialysis-related costs (ICU: $22,656; dialysis: $6,873) vs. TERLIVAZ plus albumin (ICU: $6,382; dialysis: $5,068). The HRS reversal rate for those treated with TERLIVAZ plus albumin was higher than those treated with midodrine and octreotide plus albumin (55.56%; n=15/27 vs. 4.76%; n=1/21), and those treated with norepinephrine plus albumin (55.64%; n=74/133 vs. 26.92%; n=35/130). For every two patients treated with TERLIVAZ plus albumin instead of midodrine and octreotide plus albumin, one additional patient was estimated to achieve HRS reversal. For every four patients treated with TERLIVAZ plus albumin instead of norepinephrine plus albumin, one additional patient was estimated to achieve HRS reversal. Collectively, these findings suggest that TERLIVAZ can be considered a cost-effective, value-based treatment option for appropriate patients with HRS with rapid reduction in kidney function.1,2 Limitations2: Efficacy, safety, and treatment-related adverse event data were sourced from published head-to-head randomized clinical trials, which may not be generalizable to the entire adult HRS population and differed from the adverse events in the FDA-approved TERLIVAZ label. Verified HRS reversal, the primary endpoint of the CONFIRM trial for TERLIVAZ (NCT02770716), was not used in this analysis. Several assumptions for the model were made, including the proportion of patients treated on the general floor with midodrine and octreotide plus albumin, and norepinephrine plus albumin. Cost data from public sources may be different from the actual costs of a hospital/institution and may not reflect discounts or rebates offered by manufacturers. The analysis focuses on the treatment-related cost of care over 14 days of the initial hospitalization and due to the short time horizon, other mid- and long-term benefits of HRS reversal post-initial hospitalization are not captured, including the reduced need for dialysis, kidney transplantation, and better outcomes post-liver transplantation. This study was funded by Mallinckrodt Pharmaceuticals. INDICATION AND LIMITATION OF USE TERLIVAZ® is indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function. Patients with a serum creatinine >5 mg/dL are unlikely to experience benefit. IMPORTANT SAFETY INFORMATION WARNING: SERIOUS OR FATAL RESPIRATORY FAILURE TERLIVAZ may cause serious or fatal respiratory failure. Patients with volume overload or with acute-on-chronic liver failure (ACLF) Grade 3 are at increased risk. Assess oxygenation saturation (e.g., SpO2) before initiating TERLIVAZ. Do not initiate TERLIVAZ in patients experiencing hypoxia (e.g., SpO2 <90%) until oxygenation levels improve. Monitor patients for hypoxia using continuous pulse oximetry during treatment and discontinue TERLIVAZ if SpO2 decreases below 90%. Contraindications TERLIVAZ is contraindicated: In patients experiencing hypoxia or worsening respiratory symptoms. In patients with ongoing coronary, peripheral, or mesenteric ischemia. Warnings and Precautions Serious or Fatal Respiratory Failure: Obtain baseline oxygen saturation and do not initiate TERLIVAZ in hypoxic patients. Monitor patients for changes in respiratory status using continuous pulse oximetry and regular clinical assessments. Discontinue TERLIVAZ in patients experiencing hypoxia or increased respiratory symptoms. Manage intravascular volume overload by reducing or discontinuing the administration of albumin and/or other fluids and through judicious use of diuretics. Temporarily interrupt, reduce, or discontinue TERLIVAZ treatment until patient volume status improves. Avoid use in patients with ACLF Grade 3 because they are at significant risk for respiratory failure. Ineligibility for Liver Transplant: TERLIVAZ-related adverse reactions (respiratory failure, ischemia) may make a patient ineligible for liver transplantation, if listed. For patients with high prioritization for liver transplantation (e.g., MELD ≥35), the benefits of TERLIVAZ may not outweigh its risks. Ischemic Events: TERLIVAZ may cause cardiac, cerebrovascular, peripheral, or mesenteric ischemia. Avoid use of TERLIVAZ in patients with a history of severe cardiovascular conditions or cerebrovascular or ischemic disease. Discontinue TERLIVAZ in patients who experience signs or symptoms suggestive of ischemic adverse reactions. Embryo-Fetal Toxicity: TERLIVAZ may cause fetal harm when administered to a pregnant woman. If TERLIVAZ is used during pregnancy, the patient should be informed of the potential risk to the fetus. Adverse Reactions The most common adverse reactions (≥10%) include abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea. Please click here to see full Prescribing Information, including Boxed Warning. About Hepatorenal Syndrome (HRS) Hepatorenal syndrome (HRS) involving rapid reduction in kidney function1 is an acute and life-threatening condition that occurs in people with advanced liver disease.3 HRS is classified into two distinct types – a rapidly progressive type that leads to acute renal failure where patients are typically hospitalized for their care and a more chronic type that progresses over weeks to months.3 HRS involving rapid reduction in kidney function1 is estimated to affect more than 42,000 Americans annually and rates of HRS hospitalizations are increasing.4 If left untreated, HRS with rapid reduction in kidney function1 has a median survival time of less than two weeks and greater than 80 percent mortality within three months.5 ABOUT MALLINCKRODT Mallinckrodt is a global business consisting of multiple wholly owned subsidiaries that develop, manufacture, market and distribute specialty pharmaceutical products and therapies. The company's Specialty Brands reportable segment's areas of focus include autoimmune and rare diseases in specialty areas like neurology, rheumatology, hepatology, nephrology, pulmonology, ophthalmology, and oncology; immunotherapy and neonatal respiratory critical care therapies; analgesics; cultured skin substitutes and gastrointestinal products. Its Specialty Generics reportable segment includes specialty generic drugs and active pharmaceutical ingredients. To learn more about Mallinckrodt, visit . CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING STATEMENTS This release contains forward-looking statements, including with regard to TERLIVAZ®, its potential to improve health and treatment outcomes, and its potential impact on patients. The statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those in the forward-looking statements: the effects of Mallinckrodt's recent emergence from bankruptcy; satisfaction of, and compliance with, regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; issues with product quality, manufacturing or supply, or patient safety issues or adverse side effects or adverse reactions associated with TERLIVAZ; and other risks identified and described in more detail in the "Risk Factors" section of Mallinckrodt's most recent Annual Report on Form 10-K and other filings with the SEC, all of which are available on its website. The forward-looking statements made herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to update or revise any forward-looking statement, whether as a result of new information, future events and developments or otherwise, except as required by law. CONTACT Media Inquiries Green Room Communications 954-816-6003 [email protected] Investor Relations Daniel J. Speciale Senior Vice President, Finance and Chief Financial Officer, Specialty Generics 314-654-3638 [email protected] Derek Belz Vice President, Investor Relations 314-654-3950 [email protected] Mallinckrodt, the "M" brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. ©2023 Mallinckrodt. US-2300825 12/23 References 1 TERLIVAZ® (terlipressin) for Injection. Prescribing Information. Mallinckrodt Hospital Products Inc. 2023. 2 Huang X, et al. Treatment-Related Cost Analysis of Terlipressin for Adults with Hepatorenal Syndrome with Rapid Reduction in Kidney Function. Adv Ther. 2023;40:5432–5446. 3 National Organization for Rare Disorders. Hepatorenal Syndrome. Available at: . Accessed December 2023. 4 Singh J, Dahiya DS, Kichloo A, Singh G, Khoshbin K, Shaka H. Hepatorenal Syndrome: A Nationwide Trend Analysis from 2008 to 2018. Annals of Med. 2021;53: 2018-2024. doi.org/10/1080/07853890 5 Flamm, S.L., Brown, K., Wadei, H.M., et al. The Current Management of Hepatorenal Syndrome–Acute Kidney Injury in the United States and the Potential of Terlipressin. Liver Transpl. 2021;27:1191-1202. . SOURCE Mallinckrodt plc

Clinical ResultDrug Approval

30 Sep 2022

·www.biospace.com

Inspector General: 104 Accelerated Approvals Have Incomplete Confirmatory Trials

Mark Van Scyoc/Shutterstock The U.S. Department of Health and Human Services Office of Inspector General found that of 278 accelerated approvals between 1992 and 2021, 104 had incomplete confirmatory trials, according to a report issued Thursday. The report notes that one-quarter, or 70, of all accelerated approvals, occurred in 2020 and 2021. The 139 applications that had completed confirmatory trials took an average of 48 months to be finished. Of the 104 with incomplete confirmatory trials, 34% are past their initially planned dates of completion. They are, on average, 20 months past their expected completion dates. The FDA’s accelerated approval pathway allows the agency to approve certain drugs for serious or life-threatening diseases that offer benefit over existing treatments before the confirmatory trials are finished. They are typically based on surrogate endpoints, such as biomarkers that infer benefit, but for which actual clinical benefit is not proven. Accelerated approvals require companies to conduct post-approval clinical trials to validate the drugs’ clinical benefit or the approval may be rescinded. The FDA approved Biogen’s Aduhelm (aducanumab) for Alzheimer’s disease in June 2021 under an accelerated approval pathway. The approval was largely based on proof the drug decreased beta-amyloid levels in the brain, rather than proof it slowed progress of the disease. Medicare subsequently issued an advisory it would only reimburse for the drug in the context of a confirmatory trial. As a result, the IG decided to initiate an analysis of the FDA’s accelerated approvals process. The report cited four approvals that are particularly delayed: • Viatris’ Sulfamylan, which is 140 months past its original planned date. The drug is a topical antimicrobial for burns. • Takeda’s Proamatine (midodrine hydrochloride) for postural hypotension is 85 months past the originally planned date. • Acrotech Biopharma's Folatyn (pralatrexate) for T-cell lymphoma is 72 months past its planned confirmatory date. • Covis Pharma’s Makena (hydroxyprogesterone caproate) to reduce risk of preterm birth is 64 months past the original planned date. Francesco Tallarico, general counsel at Covis Pharma, told BioSpace that the Meis study demonstrated clinical benefit and the PROLONG trial confirmed the drug’s safety profile. More than a decade of post-marketing surveillance led the company to believe “there is no sound public health reason to deprive access to the only available FDA-approved treatment to reduce the risk of preterm birth in pregnant women with a history of spontaneous preterm birth,” Tallarico said. “Covis stands ready to discuss data-driven next steps with the Agency to fully explore Makena’s benefits for U.S. patients at high-risk for preterm birth and looks forward to presenting to the Advisory Committee in October,” he added. The IG study also notes that since the inception of the pathway, 13% of all accelerated approval drug applications have been withdrawn, half since January 2021. Earlier this year, Merck voluntarily withdrew Keytruda for metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy and at least one other previous line of therapy. A week later, AstraZeneca withdrew the checkpoint inhibitor Imfinzi in bladder cancer. The Imfinzi approval was to be confirmed by the Danube trial but missed the overall survival endpoints compared to standard of care. The IG report also estimates that from 2017 to 2021, Medicare and Medicaid spent more than $18 billion for accelerated approval drugs that did not have complete confirmatory trials past their originally planned dates. The report estimates Medicare Part B and Part D spent $14 billion and Medicare Part C spent $6 billion. Additional spending for both fee-for-service and managed care was $3.6 billion. “These estimates demonstrate that Medicare and Medicaid are spending billions of dollars on drugs that have yet to verify a clinical benefit,” the report states. Several factors could be at play here. Companies are bringing in millions of dollars on these drugs and any delay only increases the amount of money raised. Also, “patients may have little incentive to enroll in a confirmatory trial when the treatment is already available,” according to the report. It additionally points to the FDA’s drug withdrawal process, which “can be lengthy and contentious.”

Accelerated Approval

30 Sep 2022

·www.biospace.com

Inspector General: 104 Accelerated Approvals Have Incomplete Confirmatory Trials

Mark Van Scyoc/Shutterstock The HHS Office of Inspector General found that of 278 accelerated approvals between 1992 and 2021, 104 had incomplete confirmatory trials, according to a report issued Thursday. Mark Van Scyoc/Shutterstock The U.S. Department of Health and Human Services Office of Inspector General found that of 278 accelerated approvals between 1992 and 2021, 104 had incomplete confirmatory trials, according to a report issued Thursday. The report notes that one-quarter, or 70, of all accelerated approvals, occurred in 2020 and 2021. The 139 applications that had completed confirmatory trials took an average of 48 months to be finished. Of the 104 with incomplete confirmatory trials, 34% are past their initially planned dates of completion. They are, on average, 20 months past their expected completion dates. The FDA’s accelerated approval pathway allows the agency to approve certain drugs for serious or life-threatening diseases that offer benefit over existing treatments before the confirmatory trials are finished. They are typically based on surrogate endpoints, such as biomarkers that infer benefit, but for which actual clinical benefit is not proven. Accelerated approvals require companies to conduct post-approval clinical trials to validate the drugs’ clinical benefit or the approval may be rescinded. The FDA approved Biogen’s Aduhelm (aducanumab) for Alzheimer’s disease in June 2021 under an accelerated approval pathway. The approval was largely based on proof the drug decreased beta-amyloid levels in the brain, rather than proof it slowed progress of the disease. Medicare subsequently issued an advisory it would only reimburse for the drug in the context of a confirmatory trial. As a result , the IG decided to initiate an analysis of the FDA’s accelerated approvals process. The report cited four approvals that are particularly delayed: • Viatris ’ Sulfamylan, which is 140 months past its original planned date. The drug is a topical antimicrobial for burns. • Takeda ’s Proamatine (midodrine hydrochloride) for postural hypotension is 85 months past the originally planned date. • Acrotech Biopharma’ s Folatyn (pralatrexate) for T-cell lymphoma is 72 months past its planned confirmatory date. • Covis Pharma ’s Makena (hydroxyprogesterone caproate) to reduce risk of preterm birth is 64 months past the original planned date. Francesco Tallarico, general counsel at Covis Pharma, told BioSpace that the Meis study demonstrated clinical benefit and the PROLONG trial confirmed the drug’s safety profile. More than a decade of post-marketing surveillance led the company to believe “there is no sound public health reason to deprive access to the only available FDA-approved treatment to reduce the risk of preterm birth in pregnant women with a history of spontaneous preterm birth,” Tallarico said. “Covis stands ready to discuss data-driven next steps with the Agency to fully explore Makena’s benefits for U.S. patients at high-risk for preterm birth and looks forward to presenting to the Advisory Committee in October,” he added. The IG study also notes that since the inception of the pathway, 13% of all accelerated approval drug applications have been withdrawn, half since January 2021. Earlier this year, Merck voluntarily withdrew Keytruda for metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy and at least one other previous line of therapy. A week later, AstraZeneca withdrew the checkpoint inhibitor Imfinzi in bladder cancer. The Imfinzi approval was to be confirmed by the Danube trial but missed the overall survival endpoints compared to standard of care. The IG report also estimates that from 2017 to 2021, Medicare and Medicaid spent more than $18 billion for accelerated approval drugs that did not have complete confirmatory trials past their originally planned dates. The report estimates Medicare Part B and Part D spent $14 billion and Medicare Part C spent $6 billion. Additional spending for both fee-for-service and managed care was $3.6 billion. “These estimates demonstrate that Medicare and Medicaid are spending billions of dollars on drugs that have yet to verify a clinical benefit,” the report states. Several factors could be at play here. Companies are bringing in millions of dollars on these drugs and any delay only increases the amount of money raised. Also, “patients may have little incentive to enroll in a confirmatory trial when the treatment is already available,” according to the report. It additionally points to the FDA’s drug withdrawal process, which “can be lengthy and contentious.”

Accelerated ApprovalDrug Approval

100 Deals associated with Midodrine Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D01307	Midodrine Hydrochloride	C01CA17	DB00211

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Hypotension	Japan	Taisho Pharmaceutical Co., Ltd.	29 Jun 1989
Hypotension, Orthostatic	Japan	Taisho Pharmaceutical Co., Ltd.	29 Jun 1989

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Neurogenic Orthostatic Hypotension	Phase 2	United States	Roberts Pharmaceutical Corp.	01 Apr 2001
Fatigue Syndrome, Chronic	Clinical	United States	Shire Pharmaceuticals Group	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03706053 (CTgov)	Phase 3	Shock, Septic \| Hypotension	10	placebo (Placebo)	ohdsqtrutr(nopxpeopiy) = rnkecomxzg mkjraxpwjo (pqehxfpfoq, hvncbkhllv - joewhhlges) View more	-	24 Sep 2025
				Midodrine Hydrochloride (Midodrine Hydrochloride 10 mg TID)	ohdsqtrutr(nopxpeopiy) = qjhsakahfc mkjraxpwjo (pqehxfpfoq, skaavsizkl - wzqmpribqv) View more
NCT02307565 (CTgov)	Phase 3	Spinal Cord Injuries \| Spinal Cord Compression	19	Placebo+Midodrine (Midodrine)	tirgnksxio(afnmdxwcfo) = hxghuenkkp fhrgiwbexk (cvtwzzyfuh, 22.7) View more	-	21 Feb 2025
				Placebo+Midodrine (Placebo)	tirgnksxio(afnmdxwcfo) = szhuxezpbu fhrgiwbexk (cvtwzzyfuh, 23.3) View more
NCT02919917 (CTgov)	Phase 2/3	Vagus Nerve Diseases \| Hypotension, Orthostatic \| Autonomic Dysreflexia	66	Midodrine Hydrochloride (Usual Care Group)	irihrhnpjf = zjifqricbs dstxcvtege (wnmaciouzu, pfaryidpfe - msnjyorjts) View more	-	21 Feb 2025
				Midodrine Hydrochloride (BP Threshold Treatment Group)	irihrhnpjf = mfsawqgqlc dstxcvtege (wnmaciouzu, twuqwltmvw - blynioesjo) View more
NCT04489589 (LIBERATE, Pubmed \| Pilot Feasibility Stud)	Phase 4	-	20	Midodrine	frdzinfpyy(wbxkkbcyll) = srqmhpizpm qebzfvvoqe (sfhonbyhqr ) View more	Positive	04 Dec 2024
				Placebo	frdzinfpyy(wbxkkbcyll) = nbuqeepxsz qebzfvvoqe (sfhonbyhqr ) View more
NCT05287100 (Pubmed \| J Pediatr Gastroenterol Nutr)	Not Applicable	Fibrosis \| Ascites	-	Midodrine plus standard medical therapies (SMTs)	bakthhvuks(ktzmesdpiy) = gdfqgcsekc ipmrtazham (fitclualtn )	Positive	01 Feb 2024
				Standard medical therapies (SMTs)	bakthhvuks(ktzmesdpiy) = smrqtjusvr ipmrtazham (fitclualtn )
NCT04396548 (Pubmed \| Anesth Analg)	Not Applicable	Anesthesia \| Hypotension	67	Midodrine group	wtodcxzblx(jmoftugbew): RR = 0.35 (95% CI, 0.14 - 0.85) View more	Positive	01 Nov 2022
				Placebo group
ESC2022	Not Applicable	Vasospasm Add-on	-	Midodrine	mbzqwpbahj(qgxvpqlioc) = No adverse event was observed in Midodrine group rlyfgxedir (hulzdrzuqa )	Positive	27 Aug 2022
				Placebo
NCT01456481 (Pubmed \| Ann Intern Med)	Phase 4	Syncope, Vasovagal	133	Midodrine	mupomsbcbj(gknnpvpxes) = fngmrsjbjf jvnrnwuhaz (ysvwjsmdsp, 2 - 36)	Positive	03 Aug 2021
				Placebo	-
NCT02307565 (Pubmed \| Spinal Cord)	Phase 3	Spinal Cord Injuries	60	Midodrine 10mg	hsgbrdzrzj(lvhiheoggw) = gyxaanivgb xyonhtknxt (cpupamuhpw )	-	17 Mar 2020
				Placebo	hsgbrdzrzj(lvhiheoggw) = ahprjzymmt xyonhtknxt (cpupamuhpw )
NCT01531959 (CTgov)	Phase 3	Critical Illness \| Hypotension	139	Midodrine (Midodrine)	kjiywdhtty(vqrjhlxhhj) = jgealkvjtg mdxifdurzx (kwzzlqnhay, bqgpwfbemw - ueizvhzpqf) View more	-	06 Sep 2019
				Placebo (Placebo)	kjiywdhtty(vqrjhlxhhj) = xvausnyhni mdxifdurzx (kwzzlqnhay, rdgdltfies - egyywdfzxm) View more

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