Avonex (recombinant IFN-β-1a) / Biogen - LARVOL DELTA

TREAT-MS: Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial (clinicaltrials.gov) - P=N/A | N=900 | Active, not recruiting | Sponsor: Johns Hopkins University | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2025 ➔ Aug 2026 | Trial primary completion date: Aug 2025 ➔ Aug 2026

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

Immunomodulators and immunosuppressants for progressive multiple sclerosis: a network meta-analysis. (PubMed, Cochrane Database Syst Rev) - "The number of people with PMS with relapses is probably slightly reduced with rituximab at two years, and interferon beta-1b at three years, compared to placebo. Both drugs are also probably associated with a slightly higher proportion of withdrawals due to adverse events, as are immunoglobulins, glatiramer acetate, natalizumab, fingolimod, siponimod, and ocrelizumab; we have high confidence that this is the case with interferon beta-1a. We found only low or very low certainty evidence relating to disability progression for the included disease-modifying treatments compared to placebo, largely due to imprecision. We are also uncertain about the effect of interventions on serious adverse events, also because of imprecision. These findings are due in part to the short follow-up of the included RCTs, which lacked detection of less common severe adverse events. Moreover, the funding source of many included studies may have introduced bias into the results. Future research on..."

Clinical • Immunomodulating • Journal • Retrospective data • Review • CNS Disorders • Multiple Sclerosis

DELIVER-MS: Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS (clinicaltrials.gov) - P4 | N=800 | Active, not recruiting | Sponsor: The Cleveland Clinic | Trial primary completion date: Apr 2030 ➔ Jul 2027

Trial primary completion date • CNS Disorders • Multiple Sclerosis

A Study to Evaluate the Safety, Tolerability, and Efficacy of BIIB017 (Peginterferon Beta-1a) in Pediatric Participants for the Treatment of Relapsing-Remitting Multiple Sclerosis (clinicaltrials.gov) - P3 | N=142 | Active, not recruiting | Sponsor: Biogen | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jul 2024 ➔ May 2027

Enrollment closed • Trial primary completion date • CNS Disorders • Multiple Sclerosis • Pediatrics

INFORM: An Observational Study to Learn About the Interferon-beta Exposure of Pregnant Women During the Second and Third Trimester in Finland and Sweden (clinicaltrials.gov) - P=N/A | N=4 | Active, not recruiting | Sponsor: Bayer | Not yet recruiting ➔ Active, not recruiting | N=100 ➔ 4 | Initiation date: Sep 2024 ➔ Mar 2024

Enrollment change • Enrollment closed • Trial initiation date • CNS Disorders • Multiple Sclerosis

Interferon-Beta-1a (FP-1201) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Fred Hutchinson Cancer Center | N=24 ➔ 0 | Not yet recruiting ➔ Withdrawn

CAR T-Cell Therapy • Enrollment change • Trial withdrawal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study to Evaluate the Safety, Tolerability, and Efficacy of BIIB017 (Peginterferon Beta-1a) in Pediatric Participants for the Treatment of Relapsing-Remitting Multiple Sclerosis (clinicaltrials.gov) - P3 | N=142 | Recruiting | Sponsor: Biogen | Trial completion date: Nov 2029 ➔ May 2027 | Trial primary completion date: Nov 2029 ➔ Jul 2024

Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis • Pediatrics

PRTOECT: A Proof-of-Concept Study to Correlate Retinal Nerve Fiber Layer Changes in Patients With Multiple Sclerosis Treated With Natalizumab or Interferon Beta 1-a (clinicaltrials.gov) - P4 | N=0 | Withdrawn | Sponsor: Biogen | N=50 ➔ 0

Enrollment change • CNS Disorders • Multiple Sclerosis

DELIVER-MS: Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS (clinicaltrials.gov) - P4 | N=800 | Active, not recruiting | Sponsor: The Cleveland Clinic | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis

INFORM: An Observational Study to Learn About the Interferon-beta Exposure of Pregnant Women During the Second and Third Trimester in Finland and Sweden (clinicaltrials.gov) - P=N/A | N=100 | Not yet recruiting | Sponsor: Bayer | Initiation date: May 2024 ➔ Sep 2024

Trial initiation date • CNS Disorders • Multiple Sclerosis

Interferon-Beta-1a (FP-1201) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy (clinicaltrials.gov) - P1/2 | N=24 | Not yet recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial completion date: Nov 2026 ➔ Oct 2027 | Initiation date: May 2024 ➔ Apr 2025 | Trial primary completion date: Nov 2026 ➔ Oct 2027

CAR T-Cell Therapy • Trial completion date • Trial initiation date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Evaluating the Use and Efficacy of Avonex and Plegridy in Pediatric Patients (AAN 2024) - "Objective:Summarize the demographic/clinical characteristics and efficacy outcomes of individuals with pediatric-onset multiple sclerosis (POMS) who were treated with Avonex or PlegridyBackground:IM interferon beta-1a (Avonex®) and peginterferon beta-1a (Plegridy®) have been shown to be effective in placebo-controlled randomized trials and real-world evidence for adults with relapsing forms of multiple sclerosis (MS). The data from this registry are consistent with previously reported clinical and MRI effects of approved interferon beta therapies more traditionally utilized in adult populations. Biogen provided funding for this study."

Clinical • CNS Disorders • Multiple Sclerosis • Pediatrics

A Study of the Efficacy and Safety of Ocrelizumab in Patients With Relapsing-Remitting Multiple Sclerosis (clinicaltrials.gov) - P2 | N=220 | Completed | Sponsor: Genentech, Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Multiple Sclerosis

Evaluating the Use and Efficacy of Avonex and Plegridy in Pediatric Patients (ACTRIMS Forum 2024) - "Background: IM interferon beta-1a (Avonex®) and peginterferon beta-1a (Plegridy®) have been shown to be effective in placebo-controlled randomized trials and real-world evidence for adults with relapsing forms of multiple sclerosis (MS). The data from this registry are consistent with previously reported clinical and MRI effects of approved interferon beta therapies more traditionally utilized in adult populations."

Clinical • CNS Disorders • Multiple Sclerosis • Pediatrics

Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis. (PubMed, Cochrane Database Syst Rev) - "We are highly confident that, compared to placebo, two-year treatment with natalizumab, cladribine, or alemtuzumab decreases relapses more than with other DMTs. We are moderately confident that a two-year treatment with natalizumab may slow disability progression. Compared to those on placebo, people with RRMS treated with most of the assessed DMTs showed a higher frequency of treatment discontinuation due to AEs: we are moderately confident that this could happen with fingolimod, teriflunomide, interferon beta-1a, laquinimod, natalizumab and daclizumab, while our certainty with other DMTs is lower. We are also moderately certain that treatment with alemtuzumab is associated with fewer discontinuations due to adverse events than placebo, and moderately certain that interferon beta-1b probably results in a slight reduction in people who experience serious adverse events, but our certainty with regard to other DMTs is lower. Insufficient evidence is available to evaluate..."

Immunomodulating • Journal • Retrospective data • Review • CNS Disorders • Multiple Sclerosis

Pregnancy Exposure Registry for Vumerity (Diroximel Fumarate) (clinicaltrials.gov) - P=N/A | N=908 | Recruiting | Sponsor: Biogen | Not yet recruiting ➔ Recruiting | N=454 ➔ 908

Enrollment change • Enrollment open • CNS Disorders • Multiple Sclerosis

Interferon-Beta-1a (FP-1201) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy (clinicaltrials.gov) - P1/2 | N=24 | Not yet recruiting | Sponsor: Fred Hutchinson Cancer Center | Initiation date: Dec 2023 ➔ Mar 2024

Trial initiation date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Adverse effects of immunotherapies for multiple sclerosis: a network meta-analysis. (PubMed, Cochrane Database Syst Rev) - "We found mostly low and very low-certainty evidence that drugs used to treat MS may not increase SAEs, but may increase withdrawals compared with placebo. The results suggest that there is no important difference in the occurrence of SAEs between first- and second-line drugs and between oral, injectable, or infused drugs, compared with placebo. Our review, along with other work in the literature, confirms poor-quality reporting of adverse events from RCTs of interventions. At the least, future studies should follow the CONSORT recommendations about reporting harm-related issues. To address adverse effects, future systematic reviews should also include non-randomized studies."

Adverse events • Journal • Retrospective data • Review • CNS Disorders • Multiple Sclerosis

Understanding risks and benefits of DMT in real-world populations: early results from OPTIMISE:MS (MSMilan 2023) - "At recruitment, 391 participants (12.1%) were taking a lowefficacy first generation DMT (interferon beta/glatiramer acetate) and 1845 (57.2%) a high-efficacy second generation therapy (natalizumab: 516, 16.0%; dimethyl fumarate: 490, 15.2%; ocrelizumab: 323, 10.0%; fingolimod: 220, 6.8%; cladribine 107, 3.3%; alemtuzumab 91, 2.8%; teriflunomide: 79, 2.4%)...Ocrelizumab was the most strongly associated with COVID-19 infection (IRR 2.5 vs Avonex, P=0.01) OPTIMISE:MS will continue to collect real-world data on the safety of MS DMTs. OPTIMISE:MS will continue to collect real-world data on the safety of MS DMTs. These data will provide insight into the predictors of treatment-related adverse events. Ongoing longitudinal data collection will increase the power of the study for detecting safety signals."

Clinical • Real-world • Real-world evidence • Herpes Zoster • Infectious Disease • Multiple Sclerosis • Nephrology • Novel Coronavirus Disease • Varicella Zoster • IFNB1

Analysis of Pregnancy Outcomes Following Exposure to Intramuscular Interferon Beta-1a: The AVONEX Pregnancy Exposure Registry. (PubMed, Drugs Real World Outcomes) - P=N/A | "This large US registry study suggests IM IFNβ-1a exposure during early pregnancy was not clinically associated with adverse pregnancy outcomes in women with multiple sclerosis. These findings help inform clinicians and patients in weighing the risks and benefits of IM IFNβ-1a use during pregnancy."

Journal • CNS Disorders • Multiple Sclerosis • IFNB1

INFORM: An Observational Study to Learn About the Interferon-beta Exposure of Pregnant Women During the Second and Third Trimester in Finland and Sweden (clinicaltrials.gov) - P=N/A | N=100 | Not yet recruiting | Sponsor: Bayer

New trial • CNS Disorders • Multiple Sclerosis

DELIVER-MS: Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS (clinicaltrials.gov) - P4 | N=800 | Recruiting | Sponsor: The Cleveland Clinic | Trial completion date: Sep 2026 ➔ Sep 2030 | Trial primary completion date: Dec 2025 ➔ Apr 2030

Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

Interferon-Beta-1a (FP-1201) to Prevent Toxicities After CD19-Directed CAR T-Cell Therapy (clinicaltrials.gov) - P1/2 | N=24 | Not yet recruiting | Sponsor: Fred Hutchinson Cancer Center

CAR T-Cell Therapy • New P1/2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Immune Modulation • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study to Evaluate Oral BIIB061 Added to Interferon-beta1 (IFN-β1) or Glatiramer Acetate in Relapsing Multiple Sclerosis (RMS) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Biogen | N=300 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • CNS Disorders • Multiple Sclerosis

Status of Outcome-Based Contracts Amongst US Payers (ISPOR 2023) - "ZYNTEGLO®, Trulicity®, reSET-O®, ENTRESTO®, ONPATTRO®, AVONEX®, VUMERITY®, and TYSABRI® are some examples. Results indicate that payers are interested but do not have OBCs for most of their plan lives due to a lack of measurable outcomes and minimal risk sharing. While some express a plan to increase in the future, not all payers will be willing to adopt unless they are easy to interpret and risk sharing from manufacturers is expanded."

Cardiovascular • Diabetes • Hematological Disorders • Hemophilia • Metabolic Disorders • Rare Diseases