An Open-label, Parallel, Phase 3, Two-arm Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged 1 to Less Than 12 Years With Hemophilia A or B With or Without Inhibitory Antibodies to Factors VIII or IX

This is a parallel, Phase 3, two-arm, open-label study to evaluate the efficacy and safety of treatment with fitusiran prophylaxis administered to male pediatric participants (aged 1 to <12 years) who have severe hemophilia A or B, with or without inhibitory antibodies to FVIII or FIX.
Number of participants:
Approximately 85 participants will be enrolled into the study:
* Approximately 60 fitusiran-naïve participants with severe hemophilia A or B, with or without inhibitors (fitusiran-naïve arm), and
* Approximately 25 participants with severe hemophilia A or B with inhibitors rolling over from the EFC15467* dose confirmation study (roll-over arm).
* Fitusiran has been investigated in the pediatric population in study EFC15467, which enrolled male participants aged 1 to <12 years with hemophilia A or B with inhibitors to examine the safety and tolerability of fitusiran in the pediatric population.
Participants will be enrolled into 1 of 2 arms:
* Fitusiran-naïve: these participants have not previously received fitusiran, and they will undergo screening and study eligibility assessments. Once enrolled, they will go through a 24-week standard of care (SOC) period before starting fitusiran prophylaxis.
* Roll-over participants from the EFC15467 study: only participants who are still on active treatment in study EFC15467 and consenting to study EFC17905 will be eligible to roll over. They will not need to undergo screening or further eligibility assessments. They will directly enroll into the fitusiran treatment period and continue treatment on their current fitusiran dose.
The duration of fitusiran treatment will be up to 160 weeks for the fitusiran-naïve arm and up to 60 weeks for the roll-over arm.

Start Date18 Dec 2025

Sponsor / Collaborator

Sanofi

NCT06145373

/ RecruitingPhase 4

An Open-label, Single-arm Treatment Study to Investigate the Safety and Tolerability of Switching From Emicizumab to Fitusiran Prophylaxis in Male Participants Aged ≥12 Years of Age With Severe Hemophilia A, With or Without Inhibitors

This is an exploratory, single group, Phase 4, study to assess treatment with fitusiran prophylaxis after switching from emicizumab prophylaxis.
This study aims to evaluate the safety and tolerability of switching to fitusiran after a transition period from the last dose of emicizumab. The study will be conducted in male participants with severe hemophilia A, with or without inhibitors, aged ≥12 years, who were previously receiving emicizumab prophylaxis.
Study details include:
* The study duration will be up to approximately 28 months:
* There will be an approximately 2-month screening period.
* There will be an approximately 2-month period before fitusiran treatment starts (pre-fitusiran treatment period)
* The fitusiran treatment duration will be up to 18-months (fitusiran treatment period)
* The antithrombin (AT) follow-up (FU) period will be approximately 6 months after the last dose of fitusiran (during which the AT activity level will be monitored at approximately monthly intervals following the final fitusiran dose until AT activity levels return to at least 60%).
* The study site visits are scheduled at monthly/ every 2 months intervals of 28 days (4 weeks) / 56 days (8 weeks), respectively, during the fitusiran treatment period.

Start Date01 Mar 2024

Sponsor / Collaborator

Sanofi

NCT05662319

/ Active, not recruitingPhase 3

A Phase 3, Single-arm, Multicenter, Multinational, Open-label, One-way Crossover Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged ≥ 12 Years With Severe Hemophilia A or B With or Without Inhibitory Antibodies to Factor VIII or IX

This is a multicenter, multinational, open-label, one-way cross-over, Phase 3, single-arm study for treatment of hemophilia.
The purpose of this study is to measure the frequency of treated bleeding episodes with fitusiran in male adult and adolescent (≥12 years old) participants with hemophilia A or B, with or without inhibitory antibodies to factor VIII or IX who have switched from their prior standard of care treatment.
The total study duration will be up to approximately 50 months (200 weeks, 1 study month is equivalent to 4 weeks) and will include:
* A screening period up to approximately 60 days,
* A standard of care (SOC) period of approximately 6 study months (24 weeks),
* A fitusiran treatment period of approximately 36 study months (144 weeks),
* An antithrombin (AT) follow-up period of approximately 6 study months (24 weeks) but may be shorter or longer depending on individual participants AT recovery.
The frequency for telephone visits will be approximately every 2 weeks. For site visits the frequency will be approximately every 8 weeks during the SOC period and approximately every 4 weeks during the fitusiran treatment period. If applicable and if allowed by local regulation, home and/or remote visits may be conducted during the study

Start Date01 Feb 2023

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with Fitusiran

100 Translational Medicine associated with Fitusiran

100 Patents (Medical) associated with Fitusiran

Literatures (Medical) associated with Fitusiran

01 Jun 2026·Molecular Therapy-Nucleic Acids

A computational model-powered platform to inform the development of GalNAc-conjugated siRNA therapeutics

Article

Author: Cao, Kangna ; Xiao, Ying ; Fan, Xiaoqing ; Zhang, Ruijie ; Yan, Xiaoyu

N-acetylgalactosamine-conjugated small interfering RNA (GalNAc-siRNA) therapeutics have emerged as a groundbreaking modality with unparalleled efficacy for battling previously "undruggable" diseases. The unique pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of GalNAc-siRNA therapeutics provide an opportunity to leverage PK/PD modeling strategies for drug development. By utilizing the wealth of literature data, we developed and validated a mechanistic computational model-driven platform to guide the development of new GalNAc-siRNA therapeutics, optimizing their clinical translation. This platform integrates preclinical and clinical data from all seven FDA-approved GalNAc-siRNA drugs-fitusiran, givosiran, inclisiran, lumasiran, vutrisiran, nedosiran, and plozasiran-spanning multiple species (mouse, rat, monkey, and human). To enhance user accessibility, we further implemented a web-based Shiny application. The platform was used to inform the development of an investigational new angiotensinogen-silencing GalNAc-siRNA (SAL0132). Multiple PK/PD datasets from rats and monkeys were satisfactorily fitted, and extrapolated to humans. The platform successfully predicted the PK and simulated the PD profiles of SAL0132 in humans, which demonstrated model-informed strategies to support efficient drug development of this modality. In conclusion, this platform enables users to predict GalNAc-siRNA PK/PD profiles across species by inputting specific model parameters, providing a powerful resource to guide the development of next-generation GalNAc-siRNA therapeutics.

01 May 2026·British Journal of Pharmacology

Novel drugs approved by the EMA, the FDA and the MHRA in 2025: A year in review

Review

Author: Hemal H. Patel ; Nithyanandan Nagercoil ; Claudio Mauro ; Steve P. H. Alexander ; Rainer Schulz ; Miriam M. Cortese-Krott ; Stephen Ward ; Stavros Topouzis ; Barbara Stefanska ; Xin Wang ; Gary J. Stephens ; Nathalie Vergnolle ; Zsuzsanna Helyes ; Reynold A. Panettieri Jr ; Kirill Martemyanov ; Andreas Papapetropoulos ; Péter Ferdinandy

Abstract:

In the 2025 novel drug mini‐review, one can take a full measure of the ingenuity that underlies current drug design and development, despite the year's smaller harvest (46 novel drugs) compared to 2024 (53) and 2023 (70). 54% of the novel drugs are first‐in‐class (FIC). The emphasis on proteins/antibodies is maintained (~25% novel drugs in 2025), an industry trend that does not seem to abate. Fewer than half of the novel medicines address major or common disorders. Among the FIC drugs, it is worth mentioning the Na v 1.8 channel inhibitor suzetrigine, the first non‐opioid approved to palliate acute pain; the first positive allosteric modulator of transient receptor potential melastatin 8 (TRPM8), acoltremon, that increases basal tear production in dry eye disease, a globally common disorder; lerodalcibep, a ‘third generation’ adnectin inhibitor of the protease Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) to treat elevated LDL‐c; and zoliflodacin and gepotidacin, both innovatively targeting bacterial topoisomerases to treat uncomplicated urinary tract infections. Most of the approved medicines target unmet medical need areas and/or orphan indications (the latter alone accounting for 41% of the 2025 novel drugs) by applying imaginative approaches. These approaches include: the combination of two FIC drugs, the RAF/MEK clamp avutometinib paired with the FAK/Pyk2 inhibitor defactinib, to block more efficiently the RAS–RAF–MEK–ERK/FAK oncogenic pathway in low‐grade serous ovarian cancer; fitusiran, the first RNAi therapy for haemophilia, targeting for the first time the production of the natural anticoagulant anti‐thrombin in the liver; and brensocatib, which attenuates the activation of downstream neutrophil proteases by inhibiting the protease DPP1, thereby preventing lung tissue destruction in bronchiectasis. The landscape of novel drugs approved in 2025 reveals that pharmaceutical innovation continues to advance through FIC mechanisms, sophisticated therapeutic approaches, and a strong focus on unmet medical need.

01 May 2026·HemaSphere

Fitusiran treatment modulates the ratio between alpha‐ and beta‐antithrombin isoforms

Article

Author: Peter J. Lenting ; Stephanie Roullet ; Geneviève McCluskey ; Annie Harroche ; Elsa Bianchini ; Cecile V. Denis ; Delphine Borgel ; Olivier D. Christophe ; Hortense Maynadié ; Caterina Casari ; Laurent Frenzel

Abstract:

Antithrombin (AT) circulates as two distinct isoforms, alpha‐ and beta‐AT, which differ in their glycosylation profiles; alpha‐AT is fully glycosylated at positions Asn 128 , Asn 167 , Asn 187 , and Asn 224 , whereas beta‐AT lacks Asn 167 glycosylation. The ratio of alpha‐AT/beta‐AT is approximately 9:1 in plasma, with beta‐AT being a stronger inhibitor due to its increased affinity for heparin. Post‐transcriptional silencing of AT via fitusiran has been shown to efficiently ameliorate the hemostatic balance in hemophilia. In this study, we analyzed if and how fitusiran affected the distribution of alpha‐AT and beta‐AT. Using different experimental approaches (isoform‐specific activity, antigen, and immunoprecipitation assays), we were able to distinguish beta‐AT and alpha‐AT. Fitusiran treatment reduced the total AT activity to less than 20% of normal in both F8−/− ‐mice and hemophilia A patients. Compared to controls, a 3.8‐ and 3.3‐fold increase in the amount of beta‐AT activity relative to residual total AT activity was detected in F8−/− ‐mice and fitusiran‐treated patients, respectively (P < 0.0001). Furthermore, the ratio of beta‐AT/total AT antigen levels increased 1.8‐fold in the human patient samples (from 0.09 ± 0.03 to 0.16 ± 0.01; P = 0.003), which coincided with an increased intensity of the beta‐AT band detected in immunoprecipitation assays. It is noteworthy that this increase in the beta‐AT/total AT ratio significantly increased its anticoagulant potential. Finally, we measured beta‐AT/total AT ratios also in unrelated pathologies: congenital AT deficiency and advanced liver cirrhosis. Both conditions were also associated with an up to twofold higher ratio of beta‐AT/total AT. Altogether, our results demonstrate that reduced AT production modulates the ratio between beta‐AT and alpha‐AT.

News (Medical) associated with Fitusiran

08 Jun 2026

·www.fiercepharma.com

Pfizer scores FDA pediatric expansion for hemophilia treatment Hympavzi

The FDA has expanded its approval for Pfizer's hemophilia drug Hympavzi. It now will be available to a younger and broader patient population. The FDA has expanded the label for Pfizer’s subcutaneous hemophilia drug Hympavzi, now including patients age 6 and older who have hemophilia A or B.The anti-tissue factor pathway inhibitor was initially approved in October of 2024 for those age 12 and older with hemophilia A or B who have not developed the antibodies—also known as inhibitors—produced by the immune system that block or destroy infused clotting factor medications.The new expansion covers all patients 6 and older, regardless of their inhibitor status. The new nod also opens up the treatment to those 12 and older who have developed the inhibitors.Hympavzi, which is the first hemophilia medicine administered by way of a pre-filled, auto-injector pen, is administered weekly and is used as a prophylactic to reduce the risk of the painful bleeding episodes that accompany the disorder. “For children who have to deal with bleeding episodes from an early age and for people living with hemophilia who develop inhibitors, treatment options have been limited and are often burdensome,” Guy Young, M.D., the Director of the Hemostasis and Thrombosis Center at Children’s Hospital in Los Angeles, said in a release.Hympavzi provides control with “a level of simplicity this community has long needed,” Young added.Hemophilia, which prevents blood from clotting properly and can include painful bleeding in the joints, impacts more than 800,000 people worldwide, Pfizer said. Childrens’ joints have growing cartilage and bone, which makes them particularly susceptible to damage caused by the bleeding episodes, the company added.Inhibitor antibodies develop in roughly 20% of those with hemophilia A and 3% of those with hemophilia B and are associated with an increased risk of uncontrolled bleeding. Factor replacement therapies can become ineffective in those who are classified as inhibitors. The phase 3 Basis trial backed the approval of Hympavzi as a treatment for those age 12 and older with inhibitors, showing a 93% reduction in the annualized bleeding rate after patients switched from prior regimens. In the phase 3 Basis Kids trial, which included patients ages 6 to 17, annualized bleeding rates were also significantly reduced for those with and without inhibitors.Pfizer did not break out sales of Hympavzi in its first-quarter earnings report. Hympavzi was one of two hemophilia treatments Pfizer gained approval for in 2024. The other was hemophilia B gene therapy Beqvev, which was priced at $3.5 million and was removed from the market in February of last year after it failed to drum up much interest from patients or doctors. Roche’s Hemlibra is the top-selling branded hemophilia drug on the market, generating sales of 4.5 billion Swiss francs ($5.7 billion) last year. It is for those who have hemophilia A. Novo Nordisk’s once-daily subcutaneous Alhemo, for patients with hemophilia A or B, was approved in 2024. Last year, Sanofi and Alnylam gained FDA approval for Qfitlia, which is administered subcutaneously every one or two months and can be used by those with either type of hemophilia and regardless of inhibitor status.

Phase 3Drug ApprovalClinical ResultGene Therapy

13 May 2026

·allsci.com

European Commission approves Pfizer’s Hympavzi for hemophilia A and B patients with inhibitors

The European Commission has approved Pfizer’s Hympavzi (marstacimab) for hemophilia A and B patients with inhibitors. The approval means Pfizer is one of few companies offering a once-weekly subcutaneous option that covers both hemophilia subtypes in the inhibitor-positive population — a segment historically underserved by approved prophylactic therapies. The EC granted marketing authorization expanding Hympavzi’s approved indication to patients 12 years of age and older weighing at least 35 kg with hemophilia A (congenital factor VIII deficiency) with FVIII inhibitors, or hemophilia B (congenital factor IX deficiency) with FIX inhibitors. The authorization is valid across all 27 EU member states, as well as Iceland, Liechtenstein, and Norway. Pfizer said no routine treatment-related laboratory monitoring is required for this population under the approved regimen. Clinical evidence from the BASIS trial The indication extension rests on data from the Phase III BASIS trial (NCT03938792), a global, open-label, multicenter study evaluating marstacimab in adolescents and adults aged 12 to under 75 years with severe hemophilia A or moderately severe to severe hemophilia B with or without inhibitors. The inhibitor cohort included 48 participants treated during a 12-month active treatment period, compared against a six-month observational period on on-demand bypass therapy. The primary endpoint was the treated annualized bleeding rate during the active treatment period. Marstacimab produced a 93% reduction in mean treated annualized bleeding rate versus on-demand therapy (1.39 versus 19.78; p<0.0001), with superiority also demonstrated across secondary bleeding endpoints including spontaneous, joint, and target joint bleeds. An interim analysis of an open-label extension study, covering up to 41 additional months of treatment, showed mean and median treated annualized bleeding rates remained low, with a median of 0.00. Scientific context and competitive landscape Inhibitors — neutralizing antibodies that develop against factor replacement therapies — affect approximately 20% of people with hemophilia A and 3% of those with hemophilia B, rendering standard factor concentrates ineffective and substantially narrowing prophylactic options. Hympavzi targets tissue factor pathway inhibitor (TFPI), specifically its Kunitz 2 domain, through a mechanism distinct from factor replacement: rather than supplying deficient clotting factors, the drug reduces TFPI-mediated suppression of coagulation initiation, aiming to rebalance hemostasis regardless of the underlying factor deficiency. The most established approved comparator in this space is emicizumab (Hemlibra, Genentech/Roche), a bispecific antibody that mimics the cofactor function of factor VIII and is approved for hemophilia A with inhibitors. Its mechanism, however, confers no activity in hemophilia B, leaving that subgroup without an equivalent subcutaneous prophylactic option until more recently. Fitusiran (Qfitlia, Sanofi), an RNA interference therapeutic that reduces antithrombin levels, received US FDA approval in March 2025 for prophylaxis in both hemophilia A and B with or without inhibitors in patients aged 12 and older, and represents a more direct cross-indication competitor to Hympavzi given the shared patient population and subcutaneous route, though fitusiran is dosed monthly rather than weekly. Pfizer’s US regulatory position for the inhibitor indication remains pending. The company said the FDA accepted and granted Priority Review for a supplemental biologics license application to expand Hympavzi’s US label to include hemophilia A or B patients aged six and older with inhibitors, with a PDUFA action date set for Q2 2026. In the US, Hympavzi is currently approved only for patients without inhibitors aged 12 and older. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Copyright © 2026. AllSci Corp. All rights reserved.

20 Mar 2026

·www.fiercepharma.com

Sanofi backs 2 more documentary films about rare blood disorders

One of the films will follow the efforts of the Hemophilia Foundation of Nigeria, led by Megan Adediran, to increase hemophilia diagnoses via a fleet of mobile medical vans. Not long after lending its support to a documentary aimed at shining a light on the often-overlooked stories of women with hemophilia, Sanofi is continuing its film-focused collaboration with patient engagement agency Believe Limited.The French pharma is supporting another two full-length documentaries from Believe Limited about rare blood disorders, the duo announced this week.One of the films will follow the efforts of the Hemophilia Foundation of Nigeria, led by Megan Adediran, to increase hemophilia diagnoses via a fleet of mobile medical vans. The other is set in the U.S., where it will chart the barriers to widespread awareness, access and advocacy that many with hemophilia face.Both films are now in production, with release timelines still to be announced. Both releases will be accompanied by “impact campaigns, educational resources and community screenings designed to extend awareness beyond the screen,” according to the companies. “These documentaries represent more than a collaboration between Sanofi and Believe Limited, it’s a commitment to ensuring patient voices are heard, seen and felt across the rare blood disorder community,” Jeff Schaffnit, general manager of U.S. rare blood disorders at Sanofi, said in the announcement. “By bringing together these powerful stories, we’re shining a light on the shared experiences that connect patient journeys—the challenges, the resilience, and the courage it takes to navigate life with a rare blood disorder,” Schaffnit continued. “But more than that, we’re honoring the healing power of advocacy, education and community—the very forces that continue to shape how we show up for these patients every day.” Sanofi is the maker of several treatments for hemophilia, including Qfitlia, Altuviiio, Alprolix and Eloctate.Last summer, the Big Pharma announced its support for “Dismissed,” a film documenting five women’s experiences with hemophilia. The disease is typically associated with men, with many people mistakenly believing that women can only be benign carriers of the disease; Sanofi has separately joined efforts to correct that common misconception about X-linked disorders.Before that, Sanofi previously worked with Believe Limited on “Let’s Talk,” a 2020 documentary digging into the mental health struggles faced by people with bleeding disorders.

100 Deals associated with Fitusiran

External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hemophilia A	United States	Genzyme Corp.	28 Mar 2025
Hemophilia B	United States	Genzyme Corp.	28 Mar 2025

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hemophilia	Phase 3	United States	Sanofi	18 Dec 2025
Hemophilia	Phase 3	Belgium	Sanofi	18 Dec 2025
Hemophilia	Phase 3	Brazil	Sanofi	18 Dec 2025
Hemophilia	Phase 3	Romania	Sanofi	18 Dec 2025

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02554773 (OLE, ASH2025)	Phase 2/3	Hemophilia B \| Hemophilia A	71	Fitusiran	jygqdylqjb(vwrwyocqwf) = liogeurkup rsvlvapanf (nadlnjyniz ) View more	Positive	06 Dec 2025
NCT03417245 \| NCT03417102 \| NCT03754790 (ATLAS-OLE, FDA_CDER) Manual	Phase 3	Hemophilia B \| Hemophilia A	-	QFITLIA AT-DR (prior bypassing agent)	cizsedovmh(jcyvumuvtt) = kdoknehest thwsocghml (ulpnfxlkpv, 2.8 - 9.5) View more	Positive	28 Mar 2025
				On-Demand BPA (prior bypassing agent)	cizsedovmh(jcyvumuvtt) = tlpqmlyyor thwsocghml (ulpnfxlkpv, 11.8 - 31.0) View more
NCT02554773 (Pubmed) Manual	Phase 2	Hemophilia B \| Hemophilia A	34	fitusiran (AT-based dose regimen)	wwimtynitm(wejrbatpgr) = jayufofcju pfcdjcvvjv (dycvvbunma )	Positive	06 Dec 2024
				fitusiran (the original dose regimen)	wwimtynitm(wejrbatpgr) = kvskfoqwhm pfcdjcvvjv (dycvvbunma )
NCT03417102 (ATLAS-INH, Pubmed) Manual	Phase 3	Hemophilia B \| Hemophilia A	57	fitusiran	ivsxmdftsb(qsykpudnde) = vpwxzdloat rppdtgypuu (okqiqfjdyh, 1.0 - 2.7) View more	Positive	29 Apr 2023
				bypassing agents	ivsxmdftsb(qsykpudnde) = orasmkyfqf rppdtgypuu (okqiqfjdyh, 10.6 - 30.8) View more
NCT03549871 (ATLAS-PPX, GlobeNewswire) Manual	Phase 3	Hemorrhage \| Hemophilia B	80	Fitusiran	sivjixmuov(oxkygeblpo) = qpuyaccafw mmfbdukmft (yccqamtrhs ) View more	Positive	10 Jul 2022
NCT03417245 \| NCT03417102 (ATLAS-INH, ISTH2022)	Phase 3	Hemophilia inhibitors	118	Fitusiran prophylaxis	epwhbgjwkc(tnklprnwnm) = jtsbqcispp xolzhhfwmz (nxvypmtyld ) View more	-	09 Jul 2022
NCT03417102 (ISTH2022)	Phase 3	Hemophilia A	-	Fitusiran prophylaxis	nxualjywvy(tyjrlsyyme) = ekxhgzsxus oeteeuuzqu (tvpmhpluhk ) View more	-	09 Jul 2022
NCT03549871 (ATLAS-PPX, ISTH2022)	Phase 3	Hemophilia	217	fitusiran	rxaggxxahl(gtylsdlqdd) = fqtekmauwb xxtrjyxkwh (kannptecty )	-	09 Jul 2022
NCT03417245 (ATLAS-A/B, CTgov)	Phase 3	Hemophilia B \| Hemophilia A	120	factor concentrates (Factor On-demand)	xzunzzyisk = wvjdxxjixd olyblpgkmw (rlncohmthv, cksqzzahwh - oimdeqozqs) View more	-	04 Feb 2022
				factor concentrates+fitusiran (Fitusiran 80 mg Prophylaxis)	xzunzzyisk = ctvveugutm olyblpgkmw (rlncohmthv, jibncdaixw - ugtohqbjlu) View more
NCT03417102 (ATLAS-INH, CTgov)	Phase 3	Hemophilia B \| Hemophilia A	60	Bypassing agents (Bypassing Agents (BPA) On-demand)	ylhlebcibr = fgfzlbrkqk hhrfyipqyh (soqexzfgtn, dymdushmlm - kovkruofdw) View more	-	21 Dec 2021
				fitusiran (Fitusiran 80 mg Prophylaxis)	ylhlebcibr = duqzfhplhv hhrfyipqyh (soqexzfgtn, kfuqthsvxv - bzlqxavdqb) View more

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