methotrexate (ADX-2191) / Aldeyra - LARVOL DELTA

A proposed clinical trial, which received Special Protocol Assessment agreement from the U.S. Food and Drug Administration, is designed to compare cancer cell clearance after 30 days of therapy in up to 20 patients following 1:1 randomization to receive either a single intraocular injection or eight intraocular injections of ADX-2191 (Businesswire) - "The clinical trial is expected to begin in the second half of 2025 and conclude in 2026."

New trial • Primary Vitreoretinal Lymphoma

Aldeyra Therapeutics Receives Orphan Designation from the European Medicines Agency for ADX-2191 for the Treatment of Primary Large B-Cell Lymphomas of Immune-Privileged Sites, including Primary Vitreoretinal Lymphoma (Businesswire)

Orphan drug • Large B Cell Lymphoma • Primary Vitreoretinal Lymphoma

FDA grants fast track designation for Aldeyra’s eye disease drug (Investing.com) - "The potential effectiveness of ADX-2191 is supported by Phase 2 clinical trial results announced in 2023, which demonstrated improvements in retinal sensitivity following treatment. Aldeyra plans to initiate a Phase 2/3 clinical trial of the drug in 2025."

Fast track • New P2/3 trial • Retinitis Pigmentosa

Aldeyra Therapeutics Receives Orphan Designation from the European Medicines Agency for ADX-2191 for the Treatment of Inherited Retinal Dystrophies including Retinitis Pigmentosa (Aldeyra Therapeutics Press Release) - "Aldeyra Therapeutics, Inc...announced that the European Medicines Agency (EMA) has granted Orphan Designation for ADX-2191 (methotrexate intravitreal injection) for the treatment of inherited retinal dystrophies of the rod-dominant phenotype, including retinitis pigmentosa...The potential activity of ADX-2191 in retinitis pigmentosa is supported by results from a Phase 2 clinical trial, announced in 2023, which demonstrated improvements from baseline in retinal sensitivity following treatment. A planned Phase 2/3 clinical trial of ADX-2191 in retinitis pigmentosa is expected to initiate in 2025."

New P2/3 trial • Orphan drug • Retinitis Pigmentosa

Aldeyra Therapeutics Receives Special Protocol Assessment Agreement Letter from the U.S. Food and Drug Administration for ADX-2191 for the Treatment of Primary Vitreoretinal Lymphoma (Businesswire) - "Based on a pre-New Drug Application (NDA) meeting with the FDA in December 2022, Aldeyra submitted a literature-based NDA of ADX-2191 for the treatment of PVRL, which was accepted for Priority Review in March 2023. In June 2023, Aldeyra received a Complete Response Letter that stated that the available literature was not sufficient to demonstrate efficacy and that adequate and well-controlled trials were required for approval. The FDA subsequently agreed that a single clinical trial in addition to literature references will be sufficient to support NDA resubmission. The clinical trial proposed in the Special Protocol Assessment will compare cancer cell clearance after 30 days of therapy in up to 20 patients following 1:1 randomization to receive either a single intraocular injection or eight intraocular injections of ADX-2191...The clinical trial is expected to begin in the second half of 2025 and conclude in 2026."

New trial • Special protocol assessment • Primary Vitreoretinal Lymphoma

Survival Similar in AYA and Non-AYA Patients With T-ALL (Hematology Advisor) - "Adolescent and young adult (AYA) patients with T-cell acute lymphoblastic leukemia (T-ALL) demonstrated similar survival outcomes as older patients, according to an analysis of Children’s Oncology Group (COG) trials presented at the ASH Annual Meeting 2023...The study evaluated data from AYA and non-AYA patients with T-ALL, including 1562 from AALL0434 and 615 from AALL1231. Patients in both trials were treated with augmented Berlin-Frankfurt-Münster (ABFM) regimens...When the data were pooled from both studies in AYA and non-AYA categories, there was no significant difference in event-free survival (EFS; P =.05813) or overall survival (P =.1901)."

Retrospective data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

Tailoring Treatment Selection for Various Stages of NSCLC: Optimizing Patient Outcomes : Episode 15 : Impact on Outcomes of Unmet Needs in NSCLC Treatment (AJMC) - "Erin A. Gillaspie, MD, MPH, FACS: I mean, I think it goes all the way back to the very beginning at diagnosis....David Carbone, MD, PHD: We've talked about clinical trials, exploring new treatments and combination regimens in early stage and metastatic, and we could talk about them all day... Trials that allow patients with brain metastases, trials that allow patients who got one dose of methotrexate for rheumatoid arthritis 25 years before. We need to start thinking more about real-world populations in our trials and allowing these people into these trials and pushing the trials to prove or disprove the efficacy of these agents in a real-world population."

Video

Three-Drug Regimen Improves Protection against GVHD after Stem Cell Transplant (National Cancer Institute) - "Excitement about the cyclophosphamide-based regimen in people receiving well-matched transplants began when the results from the smaller trial were reported in 2019, said the trial’s lead investigator, Shernan Holtan, M.D....'I am hearing from colleagues around the globe that practice patterns are changing' based on the trial's findings, Dr. Holtan continued. 'This cyclophosphamide-based regimen could indeed become the new standard of care for [allogeneic stem cell transplants], especially considering the reduction in both severe acute and chronic GVHD.'"

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The Bladder Cancer Patient Journey : Episode 8: Don’t Be Afraid to Ask Questions Along the Bladder Cancer Journey, Patients and Clinicians Advise (Cancer Network) - "Jain: What symptoms were you experiencing that led you to seek medical care?...Jain: What were your initial concerns?"

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Phase 3 GUARD Trial of ADX-2191 (Methotrexate for Intravitreal Administration) to Prevent Proliferative Vitreoretinopathy and Other Postoperative Complications (ASRS 2023) - No abstract available

P3 data • Retinal Disorders

A Study in Subjects With Retinitis Pigmentosa (clinicaltrials.gov) - P2 | N=8 | Completed | Sponsor: Aldeyra Therapeutics, Inc. | Recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Jun 2023 | Trial primary completion date: Dec 2022 ➔ Jun 2023

Trial completion • Trial completion date • Trial primary completion date • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

ASCO 2023: Improving Genitourinary Cancer Care (Cancer Therapy Advisor) - "'The main finding of the trial is the importance of total cumulative cisplatin dose, as patients who received more than 4 cycles of chemotherapy had better survival than those who received 4 cycles or less. We can conclude that more cisplatin is needed for improved survival,' Dr Bilusic said."

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Q&A: Current gynecologic oncology drug shortage a ‘public health crisis’ (Healio) - "According to an interview with Julie R. Gralow, MD...this drug shortage was caused by the shutdown of a plant that produced raw materials for all FDA-approved U.S. manufacturers of cisplatin and carboplatin."

As Cancer Drug Shortages Increase, Patients’ Lives Are at Stake (Cancer Therapy Advisor) - "In her testimony, Julie Gralow, MD...called the current shortages 'the worst I have seen in my 30-year career.'"

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Aldeyra Therapeutics Provides Regulatory Update on ADX-2191 (Businesswire) - "Aldeyra...announced receipt of a Complete Response Letter from the U.S. Food and Drug Administration (FDA) for the 505(b)(2) New Drug Application (NDA) of ADX-2191 (methotrexate for injection, USP), an investigational drug candidate, for the treatment of primary vitreoretinal lymphoma (PVRL). Although no safety or manufacturing issues with ADX-2191 were identified, the FDA stated that there was a 'lack of substantial evidence of effectiveness' due to 'a lack of adequate and well-controlled investigations' in the literature-based NDA submission. Based on prior discussions with the FDA, Aldeyra did not conduct any clinical trials of ADX-2191 in PVRL....An Expanded Access Program allows for access to treatment options for serious diseases when other therapeutic options are not available. Aldeyra plans to discuss ADX-2191 for the treatment of PVRL with the FDA, including the potential to make ADX-2191 accessible to PVRL patients under an Expanded Access Program protocol."

FDA event • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Kris Aquino Begins Taking Anti-cancer Medication for Possible Six Autoimmune Conditions (Philstar) - "'My lead doctor...Dr. John Belperio, had a difficult time convincing me about methotrexate because physically I knew my immunity wasn't ready but when i saw my inflammatory numbers were high,' Kris shared."

Expert Perspectives on Advances in Precision Medicine in Treating Rheumatoid Arthritis : Episode 1: Treatment Options for Rheumatoid Arthritis (RA) (HCPLive) - "Vibeke Strand, MD, MACR, FACP, provides an overview of treatment options for rheumatoid arthritis....So most of the time, the first thing after methotrexate is a TNF [tumor necrosis factor] inhibitor because that's where, in fact, the formularies have moved, and that's where the cost is the most efficient."

Video

FDA Accepts for Priority Review ADX-2191 New Drug Application for the Treatment of Primary Vitreoretinal Lymphoma (Businesswire) - "Aldeyra Therapeutics, Inc...nnounced that the U.S. Food and Drug Administration (FDA) accepted for Priority Review the New Drug Application (NDA) for ADX-2191 (methotrexate injection, USP), an investigational drug candidate, for the treatment of primary vitreoretinal lymphoma. The FDA assigned a Prescription Drug User Fee Act (PDUFA) date of June 21, 2023. The FDA noted that no potential filing review issues have been identified....The NDA submission is supported by a combination of more than three decades of published literature on the safety and efficacy of methotrexate, the active ingredient of ADX‑2191, for the treatment of primary vitreoretinal lymphoma, in addition to safety data from the recently completed Phase 3 GUARD Trial of ADX-2191 in patients with proliferative vitreoretinopathy."

NDA • PDUFA date • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Aldeyra Therapeutics Submits New Drug Application to the U.S. Food and Drug Administration for ADX‑2191 for the Treatment of Primary Vitreoretinal Lymphoma (Businesswire) - "Aldeyra Therapeutics, Inc...announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for ADX‑2191 (methotrexate injection, USP), an investigational drug candidate, for the treatment of primary vitreoretinal lymphoma, a rare but potentially fatal cancer with no FDA-approved therapy...The NDA submission is supported by a combination of published literature on the safety and efficacy of methotrexate for the treatment of primary vitreoretinal lymphoma and safety data from the recently completed Phase 3 GUARD Trial of ADX‑2191 for the prevention of proliferative vitreoretinopathy....ADX-2191 has received FDA Orphan Drug Designation for the treatment of primary vitreoretinal lymphoma. In addition, as part of the NDA submission, Aldeyra requested Priority Review Designation, which reduces the review period during which the FDA aims to take action on an NDA to within 6 months, compared to 10 months under standard review."

NDA • Orphan drug • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Oncology Grand Rounds: Therapy for Muscle-Invasive Urothelial Carcinoma: Controversies and Dilemmas (MedPageToday) - P=NA | N= NA | SWOG-8710 trial (NCT02756637) | "Muscle-invasive bladder cancer (MIBC) is a biologically aggressive disease with propensity for early distant and locoregional metastases....Nevertheless, patients with MIBC routinely pose dilemmas because of comorbidities, advanced age, frailty, side effects of treatment, kidney insufficiency, etc."

Clinical data

Translating Psoriasis Guidelines into Practice - "Before we dive into our discussion, let's outline the Guideline-Based Approach to Treatment Selection....Dr. Armstrong recommends a 'proactive approach' in topical treatments. Once patients have treated psoriasis flares and maintained clearance, it is important to continue treatment of these clinically quiescent areas."

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Aldeyra Therapeutics Announces Positive Primary Vitreoretinal Lymphoma Pre-NDA Meeting with the FDA (Businesswire) - "Based on the pre-NDA meeting minutes, Aldeyra intends to request Priority Review designation, which reduces the review period in which the FDA aims to take action on an NDA to within 6 months (compared to 10 months under standard review)....In addition to the planned NDA submission for ADX-2191 in primary vitreoretinal lymphoma, a Type C meeting with the FDA to discuss the completion of clinical development of ADX-2191 for the prevention of proliferative vitreoretinopathy is planned for the first half of 2023..."

FDA event • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Aldeyra Therapeutics Announces Positive Primary Vitreoretinal Lymphoma Pre-NDA Meeting with the FDA (Businesswire) - "Aldeyra Therapeutics, Inc...announced that, following the recent receipt of official minutes from its pre-NDA (New Drug Application) meeting with the U.S. Food and Drug Administration (FDA), the Company plans to submit an NDA as soon as the end of 2022 for marketing approval of the investigational drug candidate ADX-2191 for the treatment of primary vitreoretinal lymphoma....The planned NDA submission is expected to include a combination of published literature on the safety and efficacy of methotrexate for the treatment of primary vitreoretinal lymphoma and safety data from the recently completed Phase 3 GUARD Trial of ADX-2191 in proliferative vitreoretinopathy."

NDA • CNS Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Pediatric atopic dermatitis, faster cyclosporine but longer lasting methotrexate [Google translation] (PharmaStar) - "Safety of treatment was overall reassuring, with a slightly higher number of non-serious adverse events in the methotrexate arm (407 vs 369), mainly nausea (43.1% vs 17.6%). 'We have seen this in clinical practice, but seeing this result in a trial gives us more confidence in discussing with parents,' commented session moderator Melinda Gooderham..."

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The GUARD Trial - Part 1: A Phase 3 Clinical Trial for Prevention of Proliferative Vitreoretinopathy (clinicaltrials.gov) - P3 | N=106 | Completed | Sponsor: Aldeyra Therapeutics, Inc. | Recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Jun 2022 | Trial primary completion date: Dec 2022 ➔ Jun 2022

Trial completion • Trial completion date • Trial primary completion date • Retinal Disorders