Delving into the Latest Updates on Tadalafil with Synapse

Overview

Basic Info

SummaryTadalafil, marketed under the brand name Cialis,belongs to a class of drugs called phosphodiesterase type 5 (PDE5) inhibitors, which also includes sildenafil (Viagra) and vardenafil (Levitra).Tadalafil was first approved by FDA for the treatment of erectile dysfunction (ED) on November 21, 2003. It was developed by the pharmaceutical company ICOS Corporation and marketed by Eli Lilly and Company. In addition to its approval for treating erectile dysfunction, tadalafil was also approved by the FDA for the treatment of benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension (PAH).

Drug Type

Small molecule drug

Synonyms

Tadalafil (JAN/USP/INN), 他达那非

+ [29]

Target

PDE5A

Mechanism

PDE5A inhibitors(Phosphodiesterase 5A inhibitors)

Therapeutic Areas

Respiratory DiseasesUrogenital DiseasesOther Diseases

Active Indication

Prostatic HyperplasiaFamilial Primary Pulmonary HypertensionPulmonary Arterial Hypertension+ [1]

Inactive Indication

Anemia, Sickle CellDiabetes MellitusDiabetic Gastroparesis+ [11]

Originator Organization

Eli Lilly & Co.

ICOS Corp.

Active Organization

Beijing Frozen Pharmaceutical Technology Co., Ltd.Eli Lilly Nederland BV

Viatris, Inc.

+ [6]

Inactive Organization

Lilly Asia Shanghai Representative Office

United Therapeutics Corp.

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

+ [1]

Drug Highest PhaseApproved

First Approval Date

AU (23 Oct 2002),

Erectile Dysfunction

RegulationOrphan Drug (US), Priority Review (CN)

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Structure/Sequence

Molecular FormulaC22H19N3O4

InChIKeyWOXKDUGGOYFFRN-IIBYNOLFSA-N

CAS Registry171596-29-5

BACKGROUNDThe minimally important difference (MID) in the 6-min walk test (6MWT) for pulmonary arterial hypertension (PAH) is estimated to be 33 m using distributional and anchor-based methods. Quality of life was used as the anchor. Here, we sought to determine whether the MID is predictive of clinical worsening.METHODSThis was a post hoc analysis of the pivotal clinical trial of tadalafil in PAH (n = 405) and its extension phase (n = 161). The 6MWT was determined at the end of the placebo-controlled phase of 16 weeks and dichotomized as < 33 or ≥33 m. Primary outcome was clinical worsening ascertained at 16 weeks and at 68 weeks of follow up. Cox proportional hazard analysis was used to determine the association between 6MWT and clinical worsening.RESULTSMean age for patients in the pivotal trial of tadalafil was 54 years old ( ± 15.5 yrs). There were 317 (78.3 %) female patients and 61 % with idiopathic PAH. 53 % of the patients were on background bosentan therapy. A 6MWT <33 m was associated with an increased risk of clinical worsening at 16 and 68 weeks. These results were unchanged after adjusting for age, sex, background therapy with bosentan, and tadalafil dose. There were no PAH hospitalizations during short-term and long-term follow up in patients achieving a 6MWT ≥33 m CONCLUSIONS: The 6MWT MID of 33 m is predictive of short- and long-term clinical worsening. These results further validate 33 m as a relevant MID for the 6MWT.

15 Jan 2025·The Journal of Maternal-Fetal & Neonatal MedicineQ4 · MEDICINE

Assessment of the value of measuring soluble fms-like tyrosine kinase-1 and placental growth factor levels following administration of tadalafil to treat fetal growth restriction

Q4 · MEDICINE

Article

Author: Katsuragi, Shinji ; Ikeda, Tomoaki ; Enomoto, Naosuke ; Tanaka, Kayo ; Nakamura, Masamitsu ; Takakura, Sho ; Tanaka, Hiroaki ; Koide, Keiko ; Sekizawa, Akihiko ; Maki, Shintaro

PURPOSEThe aim of this study was to measure the blood levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) before and after tadalafil treatment in patients with fetal growth restriction.MATERIALS AND METHODSMaternal blood was collected from 13 women before and 2 weeks after tadalafil administration in the TADAFER II trial. The tadalafil treatment was conducted in addition to the conventional FGR treatment. As a control, maternal blood was also collected from 11 women before and 2 weeks after conventional treatment for fetal growth restriction. Blood sFlt-1 and PlGF were measured and the sFlt-1/PlGF ratio was calculated. Student's t-test was used to statistically analyze differences in the sFlt-1 and PlGF levels, and in the sFlt-1/PlGF ratios.RESULTSIn both treatment groups, the levels of sFlt-1 and PlGF before and after treatment were not significantly different from each other. The sFlt-1/PlGF ratio was 2.0 ± 1.0 before and 17.6 ± 11.3 after treatment in the control group (p=.04). The sFlt-1/PlGF ratio was 2.2 ± 1.1 before and 22.2 ± 10.6 after tadalafil treatment in the tadalafil group (p=.06). The sFlt-1/PlGF ratios before and after tadalafil treatment were significantly increased in the control group. In both treatment groups, the sFlt-1/PlGF ratios before and after treatment were less than 38.CONCLUSIONSWe conclude that the levels of sFlt-1 and PlGF were not significantly different as a result of tadalafil treatment. Further studies are needed to understand the mechanism of action of tadalafil in the treatment of fetal growth restriction.

01 Jan 2025·Life Sciences

Neuronal nitric oxide synthase activation by tadalafil protects neurological impairments in a zebrafish larva model of hyperammonemia

Article

Author: Kumar, Rajneesh ; Singh, Damanpreet ; Dhiman, Poonam

AIMSHyperammonaemia (HA) is a metabolic disorder characterized by increased ammonia levels in the blood and is associated with severe neurological impairments. Some previous findings have shown the involvement of the nitric oxide pathway in HA-induced neurological impairments. The current study explored the impact of tadalafil on neurological impairments induced by HA in a zebrafish larval model due to its reported indirect interactions with the nitric oxide pathway.MATERIAL AND METHODSHA was induced in zebrafish larvae by ammonium acetate exposure from 2 to 9 days post fertilization (dpf). Locomotor and cognitive functions were analysed following the treatment. The levels of gamma-aminobutyric acid (GABA), glutamate, and dopamine were measured in the larval head. The expression of genes associated with apoptosis (baxa and bcl2a), selected neurotransmitter receptors and bdnf was analysed. The protein levels of CREB and nNOS were also quantified.KEY FINDINGSTadalafil incubation reversed the HA-associated locomotor and cognitive impairments in larvae. The treatment modulated GABA, dopamine, and glutamate levels. An upregulation in the expression of grin1a, gria2b, drd1b, drd2b, bdnf, and bcl2a, and downregulation of gabrz, gabrd, gabrg2 and baxa was observed following tadalafil treatment. The protein expression showed increased nNOS, p-CREB(Ser¹³³), and decreased p-nNOS(Ser⁸⁴⁷) levels in the larvae incubated with tadalafil.SIGNIFICANCEThe study concluded that tadalafil mitigates HA-induced neurological impairments by activating neuronal nitric oxide synthase. The study highlighted the possible application of tadalafil in the symptomatic management of neurological impairments in HA provided its efficacy and safety are further ensured in higher mammals.

201

News (Medical) associated with Tadalafil

14 Jan 2025

·endpts.com

FTC goes after pharma middlemen's price hikes on 'specialty' drugs

The top three pharmacy benefit managers hiked the prices of dozens of “specialty” generic drugs, some by more than 1,000% of their acquisition cost, the FTC said Tuesday in a new report. The PBMs — CVS’ Caremark, Cigna’s Express Scripts, and UnitedHealthcare’s Optum Rx — control about 80% of the total PBM market and consistently mark up the prices of mostly generic versions of cancer, HIV and other critical drugs. The FTC, which has been fighting PBMs in court and in prior investigations, found that between 2020 and 2022, 63% of the 51 specialty drugs reviewed by the FTC were reimbursed at rates marked up by more than 100% over their estimated acquisition cost, and 22% were marked up by more than 1,000%. “The FTC staff’s second interim report finds that the three major pharmacy benefit managers hiked costs for a wide range of lifesaving drugs, including medications to treat heart disease and cancer,” outgoing FTC Chair Lina Khan said in a statement . The FTC was set to discuss the report at a public meeting on Tuesday. For commercial prescriptions, the FTC says, more than twice as many drugs were marked up over 1,000% when dispensed through affiliated pharmacies for the big three PBMs when compared to unaffiliated pharmacies. “For the pulmonary hypertension drug tadalafil (generic of Adcirca), for example, pharmacies purchased the drug at an average of $27 in 2022, yet the Big 3 PBMs marked up the drug by $2,079 and paid their affiliated pharmacies $2,106, on average, for a 30-day supply of the medication on commercial claims — an average markup of over 7,700 percent,” the report says. The FTC also found the combined spread pricing income for the big three PBMs on 51 specialty drugs reviewed was $1.4 billion from 2017 through 2022. Spread pricing, which is a practice lawmakers have sought to ban, is when PBMs collect the difference between the amount they bill plan sponsor clients and the reimbursement rate they pay pharmacies. PBM reform has been a bipartisan and PhRMA-friendly issue on Capitol Hill, even though Congress was not able to get its recently crafted transparency and other reforms across the finish line. House and Senate leaders on both sides of the aisle have expressed a desire to crack down on PBMs, raising the likelihood that something will get done in the next Congress. PBMs have pushed back against the need for changes. “Any proposed policy regulating PBMs should face a simple test: Will this increase or decrease US drug costs?” a CVS spokesperson told Endpoints News via email. “Nearly all recently proposed ‘anti-PBM’ policies would ultimately increase US drug costs.”

Acquisition

12 Dec 2024

·www.globenewswire.com

Onconetix, Inc. Announces Receipt of Notice from Nasdaq Regarding Late Filing of Quarterly Report on Form 10-Q and Subsequent Filing

Cincinnati, OH, Dec. 12, 2024 (GLOBE NEWSWIRE) -- Onconetix, Inc. (NASDAQ: ONCO) (the “Company”) announced that it received a letter from The Nasdaq Capital Market (“Nasdaq”) on December 6, 2024 indicating that the Company’s failure to file its Quarterly Report on Form 10-Q for the period ended September 30, 2024 (the “Form 10-Q”) is in violation of Nasdaq’s continued listing requirements under Nasdaq Listing Rule 5250(c)(1) (the “Rule”). On December 10, 2024, the Company filed the Form 10-Q with the Securities and Exchange Commission. This announcement is made in compliance with Nasdaq Listing Rule 5810(b), which requires prompt disclosure of receipt of a deficiency notification. About Onconetix, Inc.: Onconetix is a commercial stage biotechnology company focused on the research, development and commercialization of innovative solutions for men’s health and oncology. Through our recent acquisition of Proteomedix, we own Proclarix®, an in vitro diagnostic test for prostate cancer originally developed by Proteomedix and approved for sale in the European Union (“EU”) under the In Vitro Diagnostic Regulation (“IVDR”). We also own ENTADFI, an FDA-approved, once daily pill that combines finasteride and tadalafil for the treatment of benign prostatic hyperplasia (“BPH”), a disorder of the prostate. For more information, visit www.onconetix.com. Contact Information: Onconetix, Inc.201 E. Fifth Street, Suite 1900Cincinnati, OH 45202Phone: (513) 620-4101 Investor Contact Information: Onconetix Investor RelationsEmail: investors@onconetix.com

AcquisitionDiagnostic Reagents

30 Oct 2024

·ir.unither.com

United Therapeutics Corporation Reports Third Quarter 2024 Financial Results

Three Months Ended September 30, Dollar Change Percentage Change 2024 2023 Total revenues $ 748.9 $ 609.4 $ 139.5 23 % Net income $ 309.1 $ 267.6 $ 41.5 16 % Net income, per basic share $ 6.93 $ 5.71 $ 1.22 21 % Net income, per diluted share $ 6.39 $ 5.38 $ 1.01 19 % Three Months Ended September 30, Dollar Change Percentage Change 2024 2023 Net product sales: Tyvaso DPI®(1) $ 274.6 $ 205.1 $ 69.5 34 % Nebulized Tyvaso®(1) 159.2 120.7 38.5 32 % Total Tyvaso 433.8 325.8 108.0 33 % Remodulin®(2) 128.3 131.1 (2.8 ) (2) % Orenitram® 113.2 92.0 21.2 23 % Unituxin® 61.1 51.3 9.8 19 % Adcirca® 7.0 7.3 (0.3 ) (4) % Other 5.5 1.9 3.6 189 % Total revenues $ 748.9 $ 609.4 $ 139.5 23 % (1) Net product sales include both the drug product and the respective inhalation device. (2) Net product sales include sales of infusion devices, including the Remunity® Pump. Three Months Ended September 30, 2024 2023 U.S. ROW Total U.S. ROW Total Net product sales: Tyvaso DPI(1) $ 274.6 $ — $ 274.6 $ 205.1 $ — $ 205.1 Nebulized Tyvaso(1) 145.2 14.0 159.2 118.1 2.6 120.7 Total Tyvaso 419.8 14.0 433.8 323.2 2.6 325.8 Remodulin(2) 115.4 12.9 128.3 111.6 19.5 131.1 Orenitram 113.2 — 113.2 92.0 — 92.0 Unituxin 57.6 3.5 61.1 48.8 2.5 51.3 Adcirca 7.0 — 7.0 7.3 — 7.3 Other 4.3 1.2 5.5 1.7 0.2 1.9 Total revenues $ 717.3 $ 31.6 $ 748.9 $ 584.6 $ 24.8 $ 609.4 (1) Net product sales include both the drug product and the respective inhalation device. (2) Net product sales include sales of infusion devices, including the Remunity Pump. Three Months Ended September 30, Dollar Change Percentage Change 2024 2023 Category: Cost of sales $ 81.8 $ 69.1 $ 12.7 18 % Share-based compensation expense(1) 1.3 1.0 0.3 30 % Total cost of sales $ 83.1 $ 70.1 $ 13.0 19 % (1) See Share-based compensation below. Three Months Ended September 30, Dollar Change Percentage Change 2024 2023 Category: External research and development(1) $ 51.7 $ 47.2 $ 4.5 10 % Internal research and development(2) 43.9 34.3 9.6 28 % Share-based compensation expense(3) 7.4 3.6 3.8 106 % Other(4) 0.5 (0.4 ) 0.9 225 % Total research and development expense $ 103.5 $ 84.7 $ 18.8 22 % (1) External research and development primarily includes fees paid to third parties (such as clinical trial sites, contract research organizations, and contract laboratories) for preclinical and clinical studies and payments to third-party contract manufacturers before FDA approval of the relevant product. (2) Internal research and development primarily includes salary-related expenses for research and development functions, internal costs to manufacture product candidates before FDA approval, and internal facilities-related expenses, including depreciation, related to research and development activities. (3) See Share-based compensation below. (4) Other primarily includes upfront fees and milestone payments to third parties under license agreements related to development-stage products and adjustments to the fair value of our contingent consideration obligations. Three Months Ended September 30, Dollar Change Percentage Change 2024 2023 Category: General and administrative(1) $ 100.4 $ 90.4 $ 10.0 11 % Litigation accrual 65.1 — 65.1 NM(2) Sales and marketing 20.7 20.7 — — % Share-based compensation expense(3) 33.0 16.5 16.5 100 % Total selling, general, and administrative expense $ 219.2 $ 127.6 $ 91.6 72 % (1) Excluding litigation accrual. See Litigation accrual section below. (2) Calculation is not meaningful. (3) See Share-based compensation below. Three Months Ended September 30, Dollar Change Percentage Change 2024 2023 Category: Stock options $ 8.0 $ 6.0 $ 2.0 33 % Restricted stock units 27.2 12.5 14.7 118 % Share tracking awards plan 5.9 2.1 3.8 181 % Employee stock purchase plan 0.6 0.5 0.1 20 % Total share-based compensation expense $ 41.7 $ 21.1 $ 20.6 98 % UNITED THERAPEUTICS CORPORATION CONSOLIDATED STATEMENTS OF OPERATIONS (In millions, except per share data) Three Months Ended September 30, 2024 2023 (Unaudited) Total revenues $ 748.9 $ 609.4 Operating expenses: Cost of sales 83.1 70.1 Research and development 103.5 84.7 Selling, general, and administrative 219.2 127.6 Total operating expenses 405.8 282.4 Operating income 343.1 327.0 Interest income 49.8 45.3 Interest expense (10.1 ) (15.6 ) Other income (expense), net 5.8 (4.9 ) Total other income, net 45.5 24.8 Income before income taxes 388.6 351.8 Income tax expense (79.5 ) (84.2 ) Net income $ 309.1 $ 267.6 Net income per common share: Basic $ 6.93 $ 5.71 Diluted $ 6.39 $ 5.38 Weighted average number of common shares outstanding: Basic 44.6 46.9 Diluted 48.4 49.7 SELECTED CONSOLIDATED BALANCE SHEET DATA (Unaudited, in millions) September 30, 2024 Cash, cash equivalents, and marketable investments $ 4,605.9 Total assets 7,123.1 Total liabilities 1,022.2 Total stockholders’ equity 6,100.9

Financial StatementLicense out/inASH

100 Deals associated with Tadalafil

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External Link

KEGG	Wiki	ATC	Drug Bank
D02008	Tadalafil	G04BE08	DB00820

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Prostatic Hyperplasia	US	Eli Lilly & Co.	06 Oct 2011
Familial Primary Pulmonary Hypertension	EU	Eli Lilly Nederland BV	01 Oct 2008
Familial Primary Pulmonary Hypertension	LI	Eli Lilly Nederland BV	01 Oct 2008
Familial Primary Pulmonary Hypertension	IS	Eli Lilly Nederland BV	01 Oct 2008
Familial Primary Pulmonary Hypertension	NO	Eli Lilly Nederland BV	01 Oct 2008
Pulmonary Arterial Hypertension	IS	Eli Lilly Nederland BV	01 Oct 2008
Pulmonary Arterial Hypertension	EU	Eli Lilly Nederland BV	01 Oct 2008
Pulmonary Arterial Hypertension	LI	Eli Lilly Nederland BV	01 Oct 2008
Pulmonary Arterial Hypertension	NO	Eli Lilly Nederland BV	01 Oct 2008
Erectile Dysfunction	AU	Eli Lilly Australia Pty Ltd.	23 Oct 2002

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertension	Discovery	IT	Eli Lilly & Co.	01 Dec 2005
Hypertension	Discovery	CA	Eli Lilly & Co.	01 Dec 2005
Hypertension	Discovery	JP	Eli Lilly & Co.	01 Dec 2005
Hypertension	Discovery	IE	Eli Lilly & Co.	01 Dec 2005
Hypertension	Discovery	US	Eli Lilly & Co.	01 Dec 2005
Hypertension	Discovery	GB	Eli Lilly & Co.	01 Dec 2005
Hypertension	Discovery	FR	Eli Lilly & Co.	01 Dec 2005
Diabetes Mellitus	Discovery	DE	Eli Lilly & Co.	01 Oct 2004
Spinal Cord Injuries	Discovery	US	Eli Lilly & Co.	01 Sep 2004
Erectile Dysfunction	Discovery	BR	Eli Lilly & Co.	01 Nov 2002

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESC2024	Not Applicable	Pulmonary Arterial Hypertension	-	Selexipag+macitentan+tadalafil	(hokbctgzxm) = aracoiybkl wswqdmlwgb (tdeexnaagr ) View more	-	02 Sep 2024
				Selexipag+macitentan+sildenafil	(hokbctgzxm) = eykbemrplv wswqdmlwgb (tdeexnaagr ) View more
FDA_CDER Manual	Not Applicable	Erectile Dysfunction	402	Placebo (Study A + US Trials)	vlpearexfl(abvzrwhbsz) = kngdksafgm qzrzzfxxac (xbdiurmfwj ) View more	Positive	28 Jun 2024
				Tadalafil 20 mg (Study A + US Trials)	vlpearexfl(abvzrwhbsz) = qdqyhixqek qzrzzfxxac (xbdiurmfwj ) View more
FDA_CDER Manual	Not Applicable	Erectile Dysfunction	1,112	Placebo (Outside the US)	fpsrncmzdf(jqdcjhperl) = euhehdcrat hrdvgwfabt (qoeydnslhi, 0.7) View more	Positive	28 Jun 2024
				Tadalafil 5 mg (Outside the US)	fpsrncmzdf(jqdcjhperl) = ifgkapcxso hrdvgwfabt (qoeydnslhi, 4.0) View more
FDA_CDER Manual	Not Applicable	Prostatic Hyperplasia	-	Placebo (Study J)	(lmubtknips) = pmkqqilhzn dedicjlotb (awwndykuxn )	Positive	28 Jun 2024
				Tadalafil 5 mg (Study J)	(lmubtknips) = ufhfcttzgj dedicjlotb (awwndykuxn )
FDA_CDER Manual	Not Applicable	Prostatic Hyperplasia \| Erectile Dysfunction	606	Placebo	(evsqmybaif) = ajjvunfiuq mzclgfmftv (eisjcvrrgc ) View more	Positive	28 Jun 2024
				Tadalafil 5 mg	(evsqmybaif) = cuoifulfhw mzclgfmftv (eisjcvrrgc ) View more
FDA_CDER Manual	Not Applicable	Prostatic Hyperplasia	696	Placebo and finasteride 5 mg	(txrufhrqeo) = afdbvdqems ymezlqfixy (sqaspgarxn ) View more	Positive	28 Jun 2024
				Tadalafil 5 mg and finasteride 5 mg	(txrufhrqeo) = bfsuimhpoh ymezlqfixy (sqaspgarxn ) View more
NCT05487755 (Pubmed) Manual	Phase 3	Diabetic Nephropathies Adjuvant	90	Tadalafil 20 mg	(iusrgexrcw) = jdihjlbxwi jievxrjkzw (qsxyvawlnl )	Positive	24 Jun 2024
				Pentoxifylline 400 mg	(iusrgexrcw) = gbroozsglr jievxrjkzw (qsxyvawlnl )
ATS2024	Not Applicable	Pulmonary Arterial Hypertension \| Chronic Disease	-	Tadalafil 40mg	(bmlnjnbzpr) = failure of the PVR to decrease is always abnormal and implies pulmonary vascular disease hqnvvcdlxf (muduimiscg ) View more	-	19 May 2024
NEWS Manual	Not Applicable	Erectile Dysfunction	635	他达拉非5mg每日一次	(tmnkjqgytg) = irrknfoims qgtbxpevki (gmdtqehrai ) View more	Positive	13 Mar 2024
MDA2024	Not Applicable	Muscular Dystrophy, Duchenne	-	Tadalafil 0.6 mg/Kg	zlodkhqpnm(tzsocwvkpv) = ftastgfsce rwacunvlrs (tcpuxcakrv, 0.8)	-	03 Mar 2024
				tadalafil (Unaffected controls)	zlodkhqpnm(tzsocwvkpv) = udtmaaqoli rwacunvlrs (tcpuxcakrv, 1.7)