The Supplementation of Vitamin A for the Prevention of Asparaginase-Associated Pancreatitis in Children With Acute Lymphoblastic Leukemia: A Prospective Single-arm Clinical Trial

Start Date01 Nov 2024

Sponsor / Collaborator-

NCT06450925 / Not yet recruitingPhase 2IIT

A Randomized Double Blinded Trial of Vitamin A Supplementation in Allogeneic Stem Cell Transplantation.

The investigators hypothesize that single oral high dose supplementation with vitamin A will reduce the incidence of moderate-severe chronic graft-versus-host disease (GVHD) compared with placebo.

Start Date01 Oct 2024

Sponsor / Collaborator

Cincinnati Children's Hospital Medical Center

NCT06508099 / RecruitingPhase 2IIT

Randomized Study of Vitamin A and D Prophylaxis Before Allogeneic Related and Unrelated Hematopoietic Stem Cell Transplantation

The therapy under investigation is the addition of 300 000 IU of vitamin A and 100 000 IU of vitamin D before conditioning. The study will include patients with malignant diseases in hematologic response with indications for allogeneic transplantation with matched related or matched unrelated donor.

Start Date15 May 2024

Sponsor / Collaborator-

100 Clinical Results associated with Vitamin A

100 Translational Medicine associated with Vitamin A

100 Patents (Medical) associated with Vitamin A

28,528

Literatures (Medical) associated with Vitamin A

01 Feb 2025·BIOMATERIALS

Local delivery of platelet-derived factors mitigates ischemia and preserves ovarian function through angiogenic modulation: A personalized regenerative strategy for fertility preservation

Article

Author: Lee, Kangwon ; Yang, Heeseon ; Song, Chae Young ; Shin, Jungwoo ; Lee, Jung Ryeol ; Chung, Nanum ; Kim, Ji Hyang ; Min, Hyewon ; Yang, Chungmo

As the most prominent and ideal modality in female fertility preservation, ovarian tissue cryopreservation, and transplantation often confront the challenge of ischemic damage and follicular loss from avascular transplantation. To surmount this impediment, we engineered a novel platelet-derived factors-encapsulated fibrin hydrogel (PFH), a paradigmatic biomaterial. PFH encapsulates autologous platelet-derived factors, utilizing the physiological blood coagulation cascade for precise local delivery of bioactive molecules. In our study, PFH markedly bolstered the success of avascular ovarian tissue transplantation. Notably, the quantity and quality of follicles were preserved with improved neovascularization, accompanied by decreased DNA damage, increased ovulation, and superior embryonic development rates under a Low-concentration Platelet-rich plasma-derived factors encapsulated fibrin hydrogel (L-PFH) regimen. At a stabilized point of tissue engraftment, gene expression analysis mirrored normal ovarian tissue profiles, underscoring the effectiveness of L-PFH in mitigating the initial ischemic insult. This autologous blood-derived biomaterial, inspired by nature, capitalizes on the blood coagulation cascade, and combines biodegradability, biocompatibility, safety, and cost-effectiveness. The adjustable properties of this biomaterial, even in injectable form, extend its potential applications into the broader realm of personalized regenerative medicine. PFH emerges as a promising strategy to counter ischemic damage in tissue transplantation, signifying a broader therapeutic prospect. (197 words).

01 Feb 2025·BIOMATERIALS

Tumor microenvironment ameliorative and adaptive nanoparticles with photothermal-to-photodynamic switch for cancer phototherapy

Article

Author: Tang, Ben Zhong ; Ding, Keke ; Zhang, Le ; Liang, Ping ; Feng, Guangxue ; Zhang, Di ; Yu, Yuewen ; Ji, Chao

The notorious tumor microenvironment (TME) usually becomes more deteriorative during phototherapeutic progress that hampers the antitumor efficacy. To overcome this issue, we herein report the ameliorative and adaptive nanoparticles (TPASIC-PFH@PLGA NPs) that simultaneously reverse hypoxia TME and switch photoactivities from photothermal-dominated state to photodynamic-dominated state to maximize phototherapeutic effect. TPASIC-PFH@PLGA NPs are designed by incorporating oxygen-rich liquid perfluorohexane (PFH) into the intraparticle microenvironment to regulate the intramolecular motions of AIE photosensitizer TPASIC. TPASIC exhibits a unique aggregation-enhanced reactive oxygen species (ROS) generation feature. PFH incorporation affords TPASIC the initially dispersed state, thus promoting active intramolecular motions and photothermal conversion efficiency. While PFH volatilization leads to nanoparticle collapse and the formation of tight TPASIC aggregates with largely enhanced ROS generation efficiency. As a consequence, PFH incorporation not only currently promotes both photothermal and photodynamic efficacies of TPASIC and increases the intratumoral oxygen level, but also enables the smart photothermal-to-photodynamic switch to maximize the phototherapeutic performance. The integration of PFH and AIE photosensitizer eventually delivers more excellent antitumor effect over conventional phototherapeutic agents with fixed photothermal and photodynamic efficacies. This study proposes a new nanoengineering strategy to ameliorate TME and adapt the treatment modality to fit the changed TME for advanced antitumor applications.

01 Jan 2025·Synthetic and Systems Biotechnology

Systematic metabolic engineering enables highly efficient production of vitamin A in Saccharomyces cerevisiae

Article

Author: Dong, Tianyu ; Wu, Nan ; Zhang, Chenglong ; Zhou, Xiao ; Lu, Shuhuan ; Shi, Yi ; Yao, Mingdong ; Xing, Shilong ; Xiao, Wenhai ; Wang, Ying ; Wang, Xinhui

Vitamin A is a micronutrient critical for versatile biological functions and has been widely used in the food, cosmetics, pharmaceutical, and nutraceutical industries. Synthetic biology and metabolic engineering enable microbes, especially the model organism Saccharomyces cerevisiae (generally recognised as safe) to possess great potential for the production of vitamin A. Herein, we first generated a vitamin A-producing strain by mining β-carotene 15,15'-mono(di)oxygenase from different sources and identified two isoenzymes Mbblh and Ssbco with comparable catalytic properties but different catalytic mechanisms. Combinational expression of isoenzymes increased the flux from β-carotene to vitamin A metabolism. To modulate the vitamin A components, retinol dehydrogenase 12 from Homo sapiens was introduced to achieve more than 90 % retinol purity using shake flask fermentation. Overexpressing POS5Δ17 enhanced the reduced nicotinamide adenine dinucleotide phosphate pool, and the titer of vitamin A was elevated by almost 46 %. Multi-copy integration of the key rate-limiting step gene Mbblh further improved the synthesis of vitamin A. Consequently, the titer of vitamin A in the strain harbouring the Ura3 marker was increased to 588 mg/L at the shake-flask level. Eventually, the highest reported titer of 5.21 g/L vitamin A in S. cerevisiae was achieved in a 1-L bioreactor. This study unlocked the potential of S. cerevisiae for synthesising vitamin A in a sustainable and economical way, laying the foundation for the commercial-scale production of bio-based vitamin A.

News (Medical) associated with Vitamin A

23 Oct 2024

·www.biospace.com

Topline Results from Alkeus Pharmaceuticals’ Study of Oral Gildeuretinol Demonstrate Significant Trend in Slowing GA Progression and Visual Function Improvement

Oral gildeuretinol demonstrated a statistically significant reduction in the geographic atrophy (GA) lesion growth rate of 15.3% from 6 to 24 months (p=0.047) in a pre-specified analysis. Gildeuretinol is the first investigational oral therapy to demonstrate a functional benefit in low luminance visual acuity (LLVA) over 24 months (p=0.031), a key secondary endpoint. Gildeuretinol showed a clinically meaningful reduction in GA lesion growth rate of 13.4% from baseline to 24 months (p=0.075), the study’s primary endpoint. Results indicate that slowing the formation of toxic vitamin A dimers could help address the high unmet need for oral therapies in multiple retinal diseases. Gildeuretinol demonstrated a favorable safety and tolerability profile. Among participants at risk of developing Choroidal Neovascularization (CNV) or wet AMD, only 11% in the gildeuretinol group experienced these adverse events compared to 44% in the placebo group, as reported by clinical investigators. CAMBRIDGE, Mass., Oct. 23, 2024 (GLOBE NEWSWIRE) -- Alkeus Pharmaceuticals, Inc., a biopharmaceutical company dedicated to preserving the sight of individuals impacted by retinal diseases, today announced that patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) treated with investigational oral therapy gildeuretinol (ALK-001) showed a statistically significant reduction in the GA lesion growth rate of 15.3% vs. placebo from 6 to 24 months (p=0.047). Gildeuretinol also demonstrated a statistically significant visual function improvement, showing 4.4 fewer letters lost (p=0.031) in low luminance visual acuity (LLVA) over 24 months. Gildeuretinol showed a clinically meaningful trend in slowing GA growth rate of 13.4% from baseline to 24 months (p=0.075), the study’s primary endpoint. A trend toward functional benefit in best corrected visual acuity (BCVA) was demonstrated with 3.3 fewer letters lost (p=0.099). Topline results of the SAGA study of gildeuretinol for the treatment of GA secondary to AMD were presented by Alexander Melamud, M.D., M.A., retina specialist and vitreoretinal surgeon with the Retina Group of Washington and a principal investigator in the SAGA study during the 128th Annual Meeting of the American Academy of Ophthalmology (AAO) held in Chicago October 18-21, 2024. “These data indicate a significant slowing of the growth rate of GA lesions, as well as reducing visual function decline,” said Seemi Khan, M.D., M.P.H., M.B.A., Chief Medical Officer of Alkeus Pharmaceuticals. “It takes a couple of months for gildeuretinol to replace vitamin A and achieve a therapeutic effect. Therefore, we are encouraged by the sensitivity analysis measuring the effect starting at six months of treatment. These data represent the first clinical demonstration that slowing vitamin A dimerization could be a target in the treatment of GA secondary to AMD. By slowing dimerization with gildeuretinol’s unique mechanism, we could reduce further damage to the retina at more advanced stages and possibly delay or prevent the onset of GA. We are excited by the potential of gildeuretinol as an oral therapy with functional benefits in GA, in addition to its potential to be the first therapy for Stargardt disease. We would like to thank the patients, investigators and trial sites for their participation in this study, as well as the National Institutes of Health National Eye Institute for providing funding for this study.” SAGA was a 24-month, double-masked, randomized, placebo-controlled trial to investigate the safety, pharmacokinetics, tolerability and efficacy in patients with GA secondary to AMD. The study enrolled 198 patients. The primary efficacy endpoint was the growth rate of GA lesions from baseline to 24 months as assessed by Fundus Autofluorescence (FAF). The first key secondary endpoint was the change in LLVA from baseline to 24 months. A favorable safety and tolerability pro demonstrated by gildeuretinol, consistent with prior clinical studies of gildeuretinol in Stargardt disease. Additionally, among participants at risk of developing Choroidal Neovascularization (CNV) or wet AMD, only 11% in the gildeuretinol group experienced these adverse events compared to 44% in the placebo group, as reported by the retina specialist investigators. “These data are meaningful and changing the conversation in the space about what might be possible with next generation treatments for patients with GA and earlier stages of AMD,” said Charles Wykoff, M.D., Ph.D., retina specialist and Director of Research at Retina Consultants of Texas. “While the primary endpoint was not met, the anatomic efficacy signal appears real, and most interestingly there appears to be a consistent signal of functional preservation with treatment. This patient population could benefit tremendously from a safe and effective systemic treatment option.” GA is a serious, progressive condition that causes irreversible loss of central vision. It is estimated that the median time of progression to severe visual impairment is slightly over six years. There is no oral therapy approved by the FDA to treat GA. The prevalence of GA in the United States is estimated to be over 1 million people, with 160,000 new cases occurring each year. “One of the most exciting aspects of these results is that gildeuretinol is the first oral medication to show a meaningful positive effect on low luminance visual acuity in macular degeneration,” Dr. Melamud said. “One of the first things patients lose in macular degeneration is low light vision, which can have a dramatic impact on daily living. The positive effect demonstrated on LLVA is significant. Based on these results, this therapy would definitely have a place in the overall strategy of treating AMD and slowing the decline observed in our patients. The favorable safety pro warrant treatment as early as possible.” About Gildeuretinol Acetate (ALK-001) Oral gildeuretinol acetate (ALK-001) is a new chemical entity designed to reduce the dimerization of vitamin A without modulating the visual cycle. In preclinical studies, gildeuretinol decreased vitamin A dimerization down to the normal rate and prevented retinal degeneration and loss of visual function in animals with Stargardt disease. A randomized, placebo-controlled, double-masked clinical trial of gildeuretinol in late-stage Stargardt patients (TEASE-1) showed clinically and statistically significant slowing of the growth of retinal lesions over two years of treatment. Additional clinical trials of gildeuretinol in Stargardt disease are ongoing. Gildeuretinol has received breakthrough therapy designation and orphan drug designation for Stargardt disease from the U.S. Food and Drug Administration. A study (SAGA) of gildeuretinol in 198 patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) demonstrated a meaningful trend in the reduction of lesion growth rate and demonstrated a functional benefit in low luminance visual acuity (LLVA). In studies, gildeuretinol demonstrated a favorable safety and tolerability profile. About Alkeus Pharmaceuticals Alkeus Pharmaceuticals, Inc. is a private biopharmaceutical company with headquarters in Cambridge, Mass., backed by institutional investors led by Bain Capital Life Sciences. Founded in 2010, Alkeus is developing therapies for serious diseases of the eye with high unmet need, with the purpose to protect the sight of individuals impacted by retinal diseases. Alkeus’ breakthrough-designated lead candidate, gildeuretinol acetate (ALK-001), is a new chemical entity currently being evaluated in clinical trials for the treatment of Stargardt disease and for geographic atrophy (GA) secondary to age-related macular degeneration (AMD). For further information, please contact: Media Relations media@alkeuspharma.com Website:

Clinical ResultOrphan DrugBreakthrough Therapy

21 Oct 2024

·www.prnewswire.com

WAINZUA (eplontersen) recommended for approval in the EU by CHMP for the treatment of adults with polyneuropathy associated with hereditary transthyretin-mediated amyloidosis

- Recommendation based on NEURO-TTRansform Phase 3 results showing WAINZUA demonstrated consistent and sustained benefit improving neuropathy impairment and quality of life versus placebo CARLSBAD, Calif., Oct. 21, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced today that Ionis' and AstraZeneca's WAINZUA (eplontersen) has been recommended for approval by the Committee for Medicinal Products for Human Use (CHMP) in the European Union (EU) for the treatment of hereditary transthyretin-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, commonly referred to as hATTR-PN or ATTRv-PN. If approved by the European Commission, WAINZUA will be the only approved medicine in the EU for the treatment of ATTRv-PN that can be self-administered monthly via an auto-injector. The CHMP based its opinion on the positive NEURO-TTRansform Phase 3 trial which showed that through 66 weeks, patients treated with WAINZUA demonstrated consistent and sustained benefit on the co-primary endpoints of serum transthyretin (TTR) concentration and neuropathy impairment measured by modified Neuropathy Impairment Score +7 (mNIS+7), and key secondary endpoint of quality of life (QoL) on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) versus external placebo. WAINZUA continued to demonstrate a favorable safety and tolerability profile throughout the NEURO-TTRansform trial. ATTRv-PN is a debilitating disease that leads to peripheral nerve damage with motor disability within five years of diagnosis and, without treatment, is generally fatal within a decade. WAINZUA is a once-monthly RNA-targeted medicine designed to reduce the production of TTR protein at its source. "Hereditary transthyretin-mediated amyloidosis with polyneuropathy remains a progressive and debilitating disease in Europe and other parts of the world, despite currently available medicines," said Brett P. Monia, Ph.D., chief executive officer, Ionis. "The CHMP recommendation is an important step toward making WAINZUA available in Europe, which, if approved, will be the only medicine in the EU for the treatment of transthyretin-mediated amyloidosis with polyneuropathy that can be self-administered monthly via an auto-injector. We are proud to partner with AstraZeneca whose global leadership and expertise positions our alliance to rapidly and effectively bring WAINZUA to many people living with hereditary transthyretin-mediated amyloidosis with polyneuropathy in Europe, pending the EMA's decision." In December 2023, eplontersen was approved in the U.S. for the treatment of ATTRv-PN, under the brand name WAINUA™ (eplontersen). WAINUA is now gaining approvals in additional countries worldwide, including Canada. As part of a global development and commercialization agreement, AstraZeneca and Ionis are commercializing WAINUA in the U.S. The companies are seeking regulatory approval in Europe and other parts of the world where AstraZeneca has exclusive rest of world commercialization and development rights. Eplontersen has also been granted Orphan Drug Designation in the U.S. and in the EU for the treatment of transthyretin-mediated amyloidosis (ATTR). Eplontersen is also currently being evaluated in the global CARDIO-TTRansform Phase 3 study for the treatment of adults with ATTR-CM. The trial is fully enrolled with more than 1,400 patients – making it the largest, most comprehensive study to date in this patient population. More information on the CARDIO-TTRansform study (NCT04136171) is available at . About TTR Amyloidosis ATTR is caused by the accumulation of liver-derived misfolded TTR protein in tissues, such as the heart and the peripheral nerves, causing organ damage and failure. ATTR then causes complications, leading to cardiovascular, neurological and renal diseases such as heart failure and chronic kidney disease. There are both hereditary (ATTRv) and non-hereditary (wild-type) forms of ATTR. ATTR is a rapidly progressive and fatal disease that requires timely recognition of symptoms. ATTR has several phenotypes including ATTR-cardiomyopathy (CM), which predominantly impacts the heart, potentially leading to heart failure, ATTR-polyneuropathy (PN), which predominantly affects the peripheral nervous system and mixed phenotype, where patients experience symptoms of both. Worldwide, there are an estimated 300,000 – 500,000 patients with ATTR-CM and about 10,000 – 40,000 patients with ATTRv-PN. About NEURO-TTRansform NEURO-TTRansform is a global, open-label, randomized trial evaluating the efficacy and safety of eplontersen in patients with ATTRv-PN at week 35, week 66 and week 85. The final analysis comparing eplontersen to an external placebo group was completed at week 66. All patients were then followed on treatment until week 85 and evaluated four weeks after the last dose in an end-of-trial assessment. Following treatment and the end-of-trial assessments, patients were eligible to enter an open-label extension study to continue receiving eplontersen once every four weeks or enter a 20-week post-treatment evaluation period, which is still ongoing. Full results from the NEURO-TTRansform trial were published in The Journal of the American Medical Association (JAMA) demonstrating the benefit of eplontersen across the spectrum of ATTRv-PN at 35, 66 and 85 weeks of treatment. About WAINZUA / WAINUA™ (eplontersen) Eplontersen is a once-monthly RNA-targeted medicine that provides upstream suppression of transthyretin (TTR) production and is designed to precisely target and reduce the production of TTR protein at its source in the liver. WAINZUA has been approved in the U.S. and Canada under the brand name WAINUA™ (eplontersen) for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults, commonly referred to as hATTR-PN or ATTRv-PN. Please see link for full U.S. Prescribing Information. WAINZUA is not yet approved for any indication in Europe. U.S. INDICATION for WAINUA™ (eplontersen) WAINUA injection for subcutaneous use 45 mg is indicated for treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. IMPORTANT SAFETY INFORMATION for WAINUA™ (eplontersen) WARNINGS AND PRECAUTIONS Reduced Serum Vitamin A Levels and Recommended Supplementation WAINUA leads to a decrease in serum vitamin A levels. Supplement with recommended daily allowance of vitamin A. Refer patient to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency occur. ADVERSE REACTIONS Most common adverse reactions (≥9% in WAINUA-treated patients) were vitamin A decreased (15%) and vomiting (9%). Please see link to U.S. Full Prescribing Information for WAINUA. About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionis.com and follow us on X (Twitter) and LinkedIn. Ionis Forward-looking Statements This press release includes forward-looking statements regarding eplontersen, Ionis' business, and the therapeutic and commercial potential of Ionis' commercial medicines, additional medicines in development and technologies. Any statement describing Ionis' goals, expectations, financial or other projections, intentions, or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended Dec. 31, 2023, and most recent Form 10-Q, which are on file with the SEC. Copies of these and other documents are available at . Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. WAINUA™ is a trademark of AstraZeneca plc. Ionis Investor Contact: D. Wade Walke, Ph.DD. [email protected] 760-603-2331 Ionis Media Contact: Daria Binder [email protected] 760-603-4679 SOURCE Ionis Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3Clinical ResultOrphan DrugDrug Approval

17 Oct 2024

·pipelinereview.com

Alnylam Submits Regulatory Application to the European Medicines Agency for Vutrisiran for the Treatment of ATTR Amyloidosis with Cardiomyopathy

− Type II Variation Submission Based on the Positive HELIOS-B Phase 3 Study in which Vutrisiran Significantly Reduced the Risk of Death and Cardiovascular Events Relative to Placebo – CAMBRIDGE, MA, USA I October 16, 2024 I Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNA interference (RNAi) therapeutics company, today announced the submission of a Type II Variation to the European Medicines Agency (EMA) for vutrisiran, an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM). Vutrisiran is the generic name for AMVUTTRA ® , which is currently approved in the European Union (EU) for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy. “Today marks another important milestone in our journey to bring RNAi therapeutics to patients with high unmet need around the world,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “ATTR-CM is a rapidly progressive, debilitating, and life-threatening disease that is an increasingly recognized cause of heart failure. Vutrisiran rapidly knocks down TTR, and in the HELIOS-B study treatment with vutrisiran substantially reduced all-cause mortality and cardiovascular events, underscoring the potential of this therapy for those living with the disease. We look forward to working closely with the EMA with the aim to bring this new treatment option to patients as soon as possible.” The regulatory application is based on positive results from the pivotal HELIOS-B Phase 3, randomized, double-blind, placebo-controlled multicenter global study which met all 10 of its primary and secondary endpoints across both the overall and monotherapy populations, each with statistical significance. The findings demonstrated the effects of vutrisiran on outcomes of mortality and cardiovascular events, as well as functional capacity (6-minute walk test), quality of life (Kansas City Cardiomyopathy Questionnaire), and heart failure symptoms and severity (NYHA class) in patients with ATTR-CM. The safety profile of vutrisiran in HELIOS-B was consistent with the established profile of the drug for hATTR amyloidosis in adult patients with polyneuropathy. In HELIOS-B, rates of adverse events (AEs), serious AEs, severe AEs and AEs leading to study drug discontinuation were similar between the vutrisiran and placebo arms. Detailed results from the HELIOS-B study were published in The New England Journal of Medicine . A supplemental New Drug Application (sNDA) for vutrisiran has been submitted to the U.S. Food and Drug Administration (FDA) for the treatment of ATTR-CM. Additional regulatory submissions are planned globally. AMVUTTRA ® (vutrisiran) INDICATION AND IMPORTANT SAFETY INFORMATION Indication In Europe and the UK, vutrisiran is indicated for the treatment of hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy. Important Safety Information Reduced Serum Vitamin A Levels and Recommended Supplementation Vutrisiran treatment leads to a decrease in serum vitamin A levels. Supplementation of approximately, but not exceeding, 2500 IU to 3000 IU vitamin A per day is advised for patients taking vutrisiran. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness). Adverse Reactions The most frequently occurring adverse reactions in patients treated with vutrisiran were pain in extremity and arthralgia. Other commonly reported adverse reactions with vutrisiran were dyspnoea, injection site reaction and increase in blood alkaline phosphatase. For additional information about vutrisiran, please see the full Summary of Product Characteristics . About AMVUTTRA ® (vutrisiran) AMVUTTRA ® (vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of variant and wild‑type transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection, vutrisiran is approved and marketed in more than 15 countries for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Vutrisiran is also in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM), which encompasses both wild-type and hereditary forms of the disease. About ATTR Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly progressive, debilitating and fatal disease caused by misfolded transthyretin (TTR) proteins, which accumulate as amyloid deposits in various parts of the body, including the nerves, heart and gastrointestinal tract. Patients may present with polyneuropathy, cardiomyopathy or both manifestations of disease. There are two different forms of ATTR – hereditary ATTR (hATTR), which is caused by a TTR gene variant and affects approximately 50,000 people worldwide, and wild-type ATTR (wtATTR), which occurs without a TTR gene variant and impacts an estimated 200,000-300,000 people worldwide. 1-4 About RNAi RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. 5 Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. 6 By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors that encode for disease-causing or disease pathway proteins – thus preventing them from being made. 5 This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases. About Alnylam Pharmaceuticals Alnylam (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “ Alnylam P 5 x25 ” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. 1 Hawkins PN, Ando Y, Dispenzeri A, et al. Ann Med . 2015;47(8):625-638. 2 Gertz MA. Am J Manag Care . 2017;23(7):S107-S112. 3 Conceicao I, Gonzalez-Duarte A, Obici L, et al. J Peripher Nerv Syst . 2016;21:5-9. 4 Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis . 2013;8:31. 5 Elbashir SM, Harborth J, Lendeckel W, et al. Nature . 2001;411(6836):494-498. 6 Zamore P. Cell . 2006;127(5):1083-1086. SOURCE: Alnylam Pharmaceuticals

Phase 3Clinical ResultDrug ApprovalsiRNANDA

100 Deals associated with Vitamin A

External Link

KEGG	Wiki	ATC	Drug Bank
D06543	Vitamin A	A11CA01	DB00162

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Ichthyosis Vulgaris	JP	Sannova KK	08 Sep 1979
Pityriasis	JP	Sannova KK	08 Sep 1979
Xerophthalmia	-	-	-

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Vitamin a Deficiency	IND Approval	US	-	12 Dec 2023

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESGO2024	Not Applicable	Hydatidiform Mole Î²-HCG	-	Vitamin A	tjahpzxfid(howubltbgn) = mnotopepzw euxqfsrruc (rcslkomocn )	Positive	10 Mar 2024
Tandem Meetings ASTCT and CIBMTR2023	Not Applicable	Chronic graft-versus-host disease	-	High-dose oral vitamin A	wopvxkkrmt(dmipxyqjsa) = oafvveqjrd wnpjxlrnim (kdhakqfxfo ) View more	Positive	01 Feb 2023
				Placebo	wopvxkkrmt(dmipxyqjsa) = cxesptcujp wnpjxlrnim (kdhakqfxfo ) View more
ASN2022	Not Applicable	Hypercalcemia	-	Vitamin A Toxicity	qzazhicmam(grvakpopnr) = jfebeqbfag zmhxdeowxl (kebpyxktzd )	-	03 Nov 2022
ARVO2022	Not Applicable	Age Related Macular Degeneration	-	Low dose Vitamin A	edvizyuseu(fzcxwqsplm) = elymhkmwsq jkecsaomvc (gfttpwtsio, 6.5)	-	01 May 2022
				Low dose Vitamin A	edvizyuseu(fzcxwqsplm) = xpplusjalg jkecsaomvc (gfttpwtsio, 10.9)
NCT01203488 (Pubmed)	Phase 3	Bronchopulmonary Dysplasia	807	Vitamin A therapy	bshjxrjkpy(ooufiigmce): RR = 0.89 (95% CI, 0.8 - 0.99)	Positive	15 May 2021
				Vitamin A (Control group)
Pubmed \| Pediatrics	Not Applicable	Bronchopulmonary Dysplasia	188	Enteral water-soluble vitamin A	orfmyntulx(zhqyxxnnbd) = mslpldvudg waelocutit (pqqfwshtwa ) View more	-	01 Jan 2021
				Placebo	orfmyntulx(zhqyxxnnbd) = uauipmatsi waelocutit (pqqfwshtwa ) View more
NCT00168610 (Pubmed \| J Nutr)	Phase 4	-	6,048	50,000 IU neonatal vitamin A	fvevsawtxs(fxeroxetha) = gqqlxkgamg qhhxcmfyvq (jfaawmicuw )	-	01 Sep 2014
				25,000 IU neonatal vitamin A	fvevsawtxs(fxeroxetha) = gdmhcidull qhhxcmfyvq (jfaawmicuw )
NCT00514891 (Pubmed \| Pediatrics)	Phase 4	-	7,587	Vitamin A supplementation	oqhaczicxx(cucntrsidu): MRR = 0.91 (95% CI, 0.59 - 1.41)	-	01 Sep 2014
				vitamin A (Placebo)
NCT00936091 (Pubmed \| Parasit Vectors)	Not Applicable	-	250	Vitamin A supplementation	nvaybvlqsk(davmpllvau) = cqtyejsyqu qbbqarlzzj (nzvgnpkvlu ) View more	Positive	15 Aug 2014
				vitamin A supplementation (Placebo)	nvaybvlqsk(davmpllvau) = jnrsrhszkg qbbqarlzzj (nzvgnpkvlu ) View more
Pubmed \| Nutrients	Not Applicable	Anemia, Iron-Deficiency	250	Vitamin A supplementation	ptxhrhwwbu(ukpvrfalxu) = aquvhiutbq bvjhpuakzt (orcmhuoamb, 28.3 - 40.2) View more	Positive	31 Dec 2013

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