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, GF-196960

+ [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

Nippon Shinyaku Co., Ltd.Eli Lilly Nederland BV

Eli Lilly & Co.

+ [5]

Inactive Organization

B BETTER LLC

United Therapeutics Corp.

Lilly Asia Shanghai Representative Office

+ [2]

Drug Highest PhaseApproved

First Approval Date

AU (23 Oct 2002),

Erectile Dysfunction

RegulationOrphan Drug (US), Priority Review (CN)

Login to view timeline

Structure/Sequence

Molecular FormulaC22H19N3O4

InChIKeyWOXKDUGGOYFFRN-IIBYNOLFSA-N

CAS Registry171596-29-5

Erectile dysfunction and lower urinary tract symptoms, from benign prostatic hyperplasia and bladder neck obstructions, are prevalent in men and associated with an increased risk of cardiovascular diseases. Phosphodiesterase-5 (PDE-5) inhibitors, such as tadalafil and sildenafil, are used to treat erectile dysfunction and may also offer cardiovascular benefits due to their vasodilatory effects. This study evaluates the impact of these PDE-5 inhibitors on all-cause mortality, cardiovascular disease, and dementia in middle-aged men with erectile dysfunction and lower urinary tract symptoms over a 3 year follow-up period.

METHODS:

This longitudinal study analyzed data from 50 million US men using the TriNetX database. Men at least 40 years of age prescribed tadalafil or sildenafil after an erectile dysfunction diagnosis, or tadalafil after lower urinary tract symptom diagnoses, from 2004 to 2021 were included. Three-year outcomes assessed included all-cause mortality, cardiovascular disease, and dementia, comparing men on PDE-5 inhibitors to those not on these medications. Propensity matching was performed for demographics and eight pre-existing conditions.

RESULTS:

The final cohort included 509,788 men with erectile dysfunction and 1,075,908 with lower urinary tract symptoms. Tadalafil and sildenafil were associated with significantly reduced risks of all-cause mortality (RR 0.66/0.76), myocardial infarction (0.73/0.83), stroke (0.66/0.78), venous thromboembolism (0.79/0.80), and dementia (0.68/0.75) in erectile dysfunction patients, with tadalafil showing more significant benefits. In lower urinary tract symptom patients, tadalafil was similarly associated with reduced mortality, cardiovascular disease, and dementia.

CONCLUSIONS:

In conclusion, tadalafil and sildenafil use in erectile dysfunction patients reduced mortality, cardiovascular disease, and dementia risks, with tadalafil providing more benefits. Tadalafil also conferred similar benefits to patients with lower urinary tract symptoms.

10 Feb 2025·The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal ObstetriciansQ4 · 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: Takakura, Sho ; Tanaka, Hiroaki ; Katsuragi, Shinji ; Ikeda, Tomoaki ; Koide, Keiko ; Nakamura, Masamitsu ; Maki, Shintaro ; Sekizawa, Akihiko ; Enomoto, Naosuke ; Tanaka, Kayo

PURPOSE:

The 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 METHODS:

Maternal 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.

RESULTS:

In 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.

CONCLUSIONS:

We 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 Feb 2025·RESPIRATORY MEDICINE

The minimally important difference in the six-minute walk test predicts clinical worsening in pulmonary arterial hypertension

Article

Author: Tharwani, Arsal ; Rao, Youlan ; Heresi, Gustavo A ; Minai, Omar ; Kim, Hyoshin

BACKGROUND:

The 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.

METHODS:

This 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.

RESULTS:

Mean 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.

204

News (Medical) associated with Tadalafil

23 Jan 2025

·www.globenewswire.com

Opella reaches study milestone for Cialis

January 21, 2025. Opella, Sanofi’s Consumer Healthcare business, announced that the US Food and Drug Administration (FDA) has lifted a clinical hold on its planned actual use trial (AUT) to support the switch of Cialis (tadalafil) from a prescription to an over-the-counter medicine. This decision allows for the initiation of the AUT and makes Cialis the first PDE-5 inhibitor to achieve this milestone. AUTs evaluate the use of the medicine under real-world conditions to identify any issues that have not previously been identified and to confirm that consumers can self-diagnose and treat themselves appropriately without the help of a healthcare provider. Julie Van Ongevalle President and CEO, Opella “We are pleased that the FDA has completed their review and is allowing us to initiate this important study. The actual use trial is not only a significant opportunity to gain insights into how Cialis is used by consumers without a prescription, but it also underscores our commitment to advancing self-care solutions. It represents a crucial step towards our commitment to make self-care as simple as it should be.” Dr. Josephine Fubara Chief Science Officer, Opella “FDA’s decision marks a significant step forward in Opella’s data-driven efforts to switch a PDE-5 inhibitor like Cialis. Now that the FDA has completed their thorough review of our data, we can move into the next phase of this program; the actual use trial, which is pivotal in ensuring the safety and proper self-selection of Cialis for over-the-counter use. We look forward to continuing our work to bring safe and expanded access to the many consumers who will benefit from nonprescription Cialis.” Opella remains committed to advancing its development program and bringing a new self-care solution with proven effectiveness for people living with erectile dysfunction. The company is completing the clinical and regulatory activities necessary to initiate the pivotal AUT. Information about the study will become available on clinicaltrials.gov. On October 21, 2024 Sanofi and CD&R announced the intention to transfer a 50% controlling stake in Opella to CD&R with Sanofi to remain a significant shareholder. Cialis (tadalafil) in the US is currently only available with a prescription. Cialis is a tablet taken to treat erectile dysfunction (ED), the signs and symptoms of benign prostatic hyperplasia (BPH), and both ED and the signs and symptoms of BPH. Cialis is the only PDE-5 inhibitor treatment that offers men a choice when it comes to treatment for ED - Cialis for use as needed and Cialis for once daily use. To learn more about Cialis, visit www.cialis.com. Cialis is not for women or children. It is important to note that Cialis is not to be taken with medicines called nitrates such as isosorbide dinitrate or isosorbide mononitrate which are often prescribed for chest pain; or with recreational drugs called poppers like amyl or butyl nitrite, as the combination may cause an unsafe drop in blood pressure; or if allergic to Cialis or Adcirca (tadalafil), or any of its ingredients. Anyone who experiences any symptoms of an allergic reaction, such as rash, hives, swelling of the lips, tongue or throat, or difficulty breathing or swallowing, should call a healthcare provider or get help right away. We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions. The content above comes from the network. if any infringement, please contact us to modify.

21 Jan 2025

·endpts.com

FDA puts Atara’s INDs on hold after rejection; Ascletis' safety data for obesity pill

Plus, news about Amylyx and Sanofi: FDA places hold on Atara Biotherapeutics’ active INDs: The holds affect the T cell therapy that the agency rejected last week as well as another program called ATA3219. According to Atara, FDA officials placed the hold due to the same manufacturing issues cited in the rejection letter . Both the company and regulators have agreed on “actions necessary to release the clinical holds.” Its stock $ATRA was down about 13% on Tuesday morning. — Max Gelman Ascletis Pharma reports early safety data for obesity pill: The biotech, which has several locations in mainland China, found that gastrointestinal-related side effects increased stepwise among five doses tested in a Phase 1 study. The company said efficacy data from the 40-person trial in the US are expected in the first quarter. — Max Bayer FDA lifts hold on Amylyx’s ALS antisense program: The move clears the way for Amylyx to start enrolling US patients in a Phase 1 study for AMX0114. The study will begin in Canada at the “beginning of 2025,” with early cohort data expected before the end of the year. — Max Gelman The regulator also lifted a hold on Sanofi’s OTC Cialis study: The pharma’s consumer health business is working on an actual use trial switching patients on Cialis from prescription to over-the-counter use, which could widen access and uptake of the erectile dysfunction treatment. Sanofi announced last year that it was selling a 50% controlling stake in the consumer business to Clayton, Dubilier & Rice, a private equity firm. — Max Bayer

Phase 1Cell TherapyClinical Result

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

100 Deals associated with Tadalafil

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D02008	Tadalafil	G04BE08	DB00820

R&D Status

Approved

10 top approved records.

Login

to view more data

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	IS	Eli Lilly Nederland BV	01 Oct 2008
Familial Primary Pulmonary Hypertension	LI	Eli Lilly Nederland BV	01 Oct 2008
Familial Primary Pulmonary Hypertension	NO	Eli Lilly Nederland BV	01 Oct 2008
Pulmonary Arterial Hypertension	EU	Eli Lilly Nederland BV	01 Oct 2008
Pulmonary Arterial Hypertension	IS	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.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Muscular Dystrophy, Duchenne	Phase 3	US	Eli Lilly & Co.	01 Sep 2013
Muscular Dystrophy, Duchenne	Phase 3	JP	Eli Lilly & Co.	01 Sep 2013
Muscular Dystrophy, Duchenne	Phase 3	AR	Eli Lilly & Co.	01 Sep 2013
Muscular Dystrophy, Duchenne	Phase 3	BE	Eli Lilly & Co.	01 Sep 2013
Muscular Dystrophy, Duchenne	Phase 3	CA	Eli Lilly & Co.	01 Sep 2013
Muscular Dystrophy, Duchenne	Phase 3	FR	Eli Lilly & Co.	01 Sep 2013
Muscular Dystrophy, Duchenne	Phase 3	DE	Eli Lilly & Co.	01 Sep 2013
Muscular Dystrophy, Duchenne	Phase 3	IT	Eli Lilly & Co.	01 Sep 2013
Muscular Dystrophy, Duchenne	Phase 3	NL	Eli Lilly & Co.	01 Sep 2013
Muscular Dystrophy, Duchenne	Phase 3	PR	Eli Lilly & Co.	01 Sep 2013

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


FDA_CDER Manual	Not Applicable	Prostatic Hyperplasia \| Erectile Dysfunction	606	Placebo	ffkwwfjsis(xpelwgpufx) = tsaakuktbf ztwlxvlwgh (szhdfafvsj ) View more	Positive	28 Jun 2024
				Tadalafil 5 mg	ffkwwfjsis(xpelwgpufx) = fmzmbqhmcp ztwlxvlwgh (szhdfafvsj ) View more
FDA_CDER Manual	Not Applicable	Erectile Dysfunction	1,112	Placebo (Outside the US)	hjbeamujfv(bwghzugjrt) = iibtbiwhki cwayyodulo (zpaxukuqnk, 0.7) View more	Positive	28 Jun 2024
				Tadalafil 5 mg (Outside the US)	hjbeamujfv(bwghzugjrt) = afsmdzfnfo cwayyodulo (zpaxukuqnk, 4.0) View more
FDA_CDER Manual	Not Applicable	Erectile Dysfunction	402	Placebo (Study A + US Trials)	gtldrlpxjn(cpssxlrwve) = blowybstav kuevxqzfri (ctytkatmoo ) View more	Positive	28 Jun 2024
				Tadalafil 20 mg (Study A + US Trials)	gtldrlpxjn(cpssxlrwve) = dmnagnhcxu kuevxqzfri (ctytkatmoo ) View more
FDA_CDER Manual	Not Applicable	Prostatic Hyperplasia	-	Placebo (Study J)	vachitqobq(pzkmfchbyq) = nyoftcpfmd viwkxcykys (wcalpstetj )	Positive	28 Jun 2024
				Tadalafil 5 mg (Study J)	vachitqobq(pzkmfchbyq) = mhimmgjibd viwkxcykys (wcalpstetj )
FDA_CDER Manual	Not Applicable	Prostatic Hyperplasia	696	Placebo and finasteride 5 mg	ijxlyallhj(qidnurkhvm) = cowtnlzpfv yysfgdghgl (rvpbcpjjpn ) View more	Positive	28 Jun 2024
				Tadalafil 5 mg and finasteride 5 mg	ijxlyallhj(qidnurkhvm) = speyfyriot yysfgdghgl (rvpbcpjjpn ) View more
NCT05487755 (Pubmed) Manual	Phase 3	Diabetic Nephropathies Adjuvant	90	Tadalafil 20 mg	cbtehrivcf(nepfiaihqx) = rhwnnbztiy puzwvohvqu (krsgaczrwn )	Positive	24 Jun 2024
				Pentoxifylline 400 mg	cbtehrivcf(nepfiaihqx) = nhnhpthkfm puzwvohvqu (krsgaczrwn )
ATS2024	Not Applicable	Pulmonary Arterial Hypertension \| Chronic Disease	-	Tadalafil 40mg	qtxlwqqzwj(ugohmiybmb) = failure of the PVR to decrease is always abnormal and implies pulmonary vascular disease ttdppidxvd (ftmspzdatf ) View more	-	19 May 2024
NEWS Manual	Not Applicable	Erectile Dysfunction	635	他达拉非5mg每日一次	eogmitbaqh(mjtjojqfpm) = kxlofzwikt hglhisrkbj (pamtmgpoth ) View more	Positive	13 Mar 2024
MDA2024	Not Applicable	Muscular Dystrophy, Duchenne	-	Tadalafil 0.6 mg/Kg	nqhooknvnm(haduvmivmf) = npwphnqyer ctrwiwtloo (qkxauifpbn, 0.8)	-	03 Mar 2024
				tadalafil (Unaffected controls)	nqhooknvnm(haduvmivmf) = iebpoeqtry ctrwiwtloo (qkxauifpbn, 1.7)
NCT05142254 (Pin Trial, ASH2023)	Phase 2	Priapism	64	Tadalafil 5mg/day and Hydroxyurea 20mg/kg/day	hohkrdlqig(eaqvizvpkb) = nfqpqexdyy qhqupfvjzf (ufmqewaygq )	Negative	10 Dec 2023
				Hydroxyurea 20mg/kg/day and Placebo	hohkrdlqig(eaqvizvpkb) = expsgrrdpi qhqupfvjzf (ufmqewaygq )