Actinium Announces Positive Full Data Results From the Pivotal Phase III SIERRA Trial

Actinium Pharmaceuticals, Inc., a pioneer in the development of targeted radiotherapies, announced positive primary and secondary endpoint results from its pivotal Phase III SIERRA trial of Iomab-B in patients aged 55 and older with active relapsed or refractory acute myeloid leukemia (r/r AML). Iomab-B achieved a high level of statistical significance (p0.0001) in the primary endpoint of durable Complete Remission (dCR) six months after initial complete remission following BMT. Iomab-B also improved the secondary endpoint of Event-Free Survival (EFS), with a 78% reduction in the probability of an event (Hazard Ratio=0.22, p0.0001).

Iomab-B doubled 1-year survival excluding cross-over patients (26.1% vs 13.1%) and median overall survival (6.4 months vs. 3.2 months). Iomab-B was well tolerated, with rates of sepsis four times lower (6.1% vs 28.6%) and lower rates of febrile neutropenia, mucositis, and acute graph versus host disease (aGVHD). Iomab-B provided unprecedented access to BMT, with 100% engraftment in patients receiving a therapeutic dose compared to 18% in the control arm, and Iomab-B produced a 75% post-BMT Complete Remission (CR) rate compared to 6.3% in the control arm. Because of the high rates of access and post-BMT CR, the primary endpoint results were highly significant. The full SIERRA findings were presented in a late-breaker session at the 2023 Tandem Meetings: Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR).

According to Dr. Sergio Giralt, Deputy Head, Division of Hematologic Malignancies and Attending Physician, Adult BMT Service at Memorial Sloan Kettering Cancer Center, “The SIERRA trial results are an exciting step forward for older patients with active r/r AML and will change the way we treat these patients. I am ecstatic that a high proportion of Iomab-B patients who achieved durable remissions have reached the critical 2-year survival mark. The SIERRA trial demonstrated that Iomab-B has the potential to become a new standard of care for active, r/r AML, with significant improvements in event-free survival and overall survival and an excellent safety profile.”

Apellis Wins FDA Approval for First Geographic Atrophy Drug

Apellis Pharmaceuticals, Inc., a global biopharmaceutical company and leader in complement, announced that SYFOVRE (pegcetacoplan injection) had been approved by the U.S. Food and Drug Administration (FDA) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). SYFOVRE is the first and only FDA-approved treatment for GA, which affects more than 1 million people in the United States and five million people worldwide.

“The approval of SYFOVRE is the most significant event in retinal ophthalmology in more than a decade,” said Eleonora Lad, M.D., Ph.D., the OAKS study’s lead investigator, director of ophthalmology clinical research, and associate professor of ophthalmology at Duke University Medical Center. “Until now, there have been no approved therapies to offer people living with GA as their vision steadily deteriorated. With SYFOVRE, we now have a safe and effective GA treatment for this debilitating disease, with progressive effects.”

“Today is a watershed moment for patients, the retina community, and Apellis. “We believe that SYFOVRE will make a meaningful difference in the lives of people with GA because of its increasing effects over time and flexible dosing,” said Cedric Francois, M.D., Ph.D., co-founder and CEO of Apellis. “GA is a complex disease that the field has spent decades trying to address, so we are humbled and proud to bring forward the first-ever treatment. Thank you to everyone who helped make this a reality.”

SYFOVRE was approved based on positive results from the Phase III OAKS and DERBY studies at 24 months in a large and representative patient population. SYFOVRE is approved for GA patients with or without subfoveal involvement and offers patients and physicians dosing flexibility with a dosing regimen of every 25 to 60 days. SYFOVRE reduced the rate of GA lesion growth compared to sham in the OAKS and DERBY studies and demonstrated increasing treatment effects over time, with the greatest benefit (up to 36% reduction in lesion growth with monthly treatment in DERBY) occurring between months 18-24. 

SYFOVRE is expected to be available in specialty distributors and specialty pharmacies across the country by the beginning of March. The European Medicines Agency is reviewing a marketing authorization application for SYFOVRE, with a decision expected in early 2024. A marketing application has also been submitted to Health Canada.

FDA Gives Green Light to Chiesi’s Lamzede

Chiesi Global Rare Diseases declared that the U.S. Food and Drug Administration had approved Lamzede for the treatment of non-central nervous system manifestations of alpha-mannosidosis in adult and pediatric patients. A lack of the enzyme α-mannosidase results in alpha-mannosidosis, an extremely rare, progressive lysosomal storage condition.

The prevalence of alpha-mannosidosis is around one in every 500,000 to one in every 1,000,000 babies born globally. Alpha-mannosidosis results in the body’s cells being unable to break down certain groups of complex sugars properly. The buildup of sugars can affect many of the body’s organs and systems. The effects of the disease vary significantly from person to person and progress over time. Symptoms may change as a patient ages,  hearing loss, including recurrent chest and ear infections, distinctive facial features, skeletal and joint abnormalities, muscle weakness, and visual & cognitive abnormalities.

Lamzede is a recombinant form of human alpha-mannosidase meant to provide natural alpha-mannosidase, an enzyme which is involved in the degradation of mannose–rich oligosaccharides to prevent their accumulation in various tissues in the body. 

Lamzede was given European Commission marketing approval in 2018 to treat mild to moderate AM patients with non-neurological symptoms.

FDA Accepts NDA and Grants Priority Review for Avacincaptad Pegol for the Treatment of Geographic Atrophy

IVERIC bio declared that the company’s New Drug Application for avacincaptad pegol, a novel experimental complement C5 inhibitor to treat geographic atrophy secondary to age-related macular degeneration, has been accepted by the U.S. Food and Drug Administration. 

The NDA has been allowed Priority Review with a Prescription Drug User Fee Act goal date of August 19, 2023. The company also declared that, at this time, the FDA had not identified any potential review issues. The FDA is not planning to hold an Advisory Committee meeting for ACP.

The 12-month pre-specified primary efficacy and safety findings from the GATHER1 and GATHER2 clinical trials served as the foundation for the NDA application. In two phases 3 pivotal trials, ACP—the only investigational treatment for GA—met the predetermined 12-month primary endpoint with reported effectiveness rates as high as 35%. ACP is also the first and only investigational treatment to be designated as a Breakthrough Treatment for GA secondary to AMD.

Pravin U. Dugel, President of Iveric Bio, said, “we believe our Special Protocol Assessment for GATHER2, rolling review, Breakthrough Therapy designation and Priority Review underscore the strength of our GATHER1 and GATHER2 results. We continue to advance our commercial launch plans and prepare for a potential approval of ACP for the treatment of geographic atrophy throughout the age-related macular degeneration disease continuum. This is vital because AMD leads to irreversible, and in many cases catastrophic, vision loss.”

FDA Approves Travere Therapeutics Kidney Disorder Drug

On February 17, 2023, Travere Therapeutics announced that the US FDA had granted accelerated approval to FILSPARI™ (sparsentan) to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g.

FILSPARI (sparsentan) is a once-daily oral medication designed to selectively target two critical pathways in the disease progression of IgAN (endothelin-1 and angiotensin II). With this approval, FILSPARI™ (sparsentan) became the first and only non-immunosuppressive therapy approved for the treatment to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression. The therapy, FILSPARI™ (sparsentan), is granted accelerated approval based on a reduction in proteinuria. However, it has not been established whether FILSPARI slows kidney function decline in patients with IgAN. The continued approval of FILSPARI may be contingent upon confirmation of a clinical benefit in the ongoing Phase 3 PROTECT Study, which is designed to demonstrate whether FILSPARI slows kidney function decline. 

As per the further update from Travere Therapeutics, the company is planning to present the topline results from the two-year confirmatory endpoints in the PROTECT Study in the fourth quarter of 2023 and looking forward to supporting the traditional approval of FILSPARI. Moreover, Travere expects FILSPARI to be available beginning the week of February 27, 2023 and will provide a comprehensive patient support program throughout the patient’s treatment journey.

IgAN is the most common type of primary glomerulonephritis worldwide and a leading cause of kidney failure due to glomerular disease. As per the assessment by DelveInsight, the total IgA Nephropathy-associated prevalent cases in the 7MM and China countries were about 1.7 million in 2021. Similarly, in the United States, nearly 150,000 people are affected by IgA Nephropathy.  IgAN is also one of the most common glomerular diseases in Europe and Japan.

Takeda Presents Phase 3 Study Result of Vedolizumab for Prevention of Intestinal aGvHD in Patients Undergoing allo-HSCT

On February 18, 2023, Takeda announced late-breaking data from the Phase 3 GRAPHITE study presented at the 2023 Tandem Meetings, demonstrating vedolizumab achieved a statistically significant and clinically meaningful improvement in lower gastrointestinal (GI) aGvHD-free survival by Day 180 after allo-HSCT with no relevant differences in safety profile versus placebo.

GRAPHITE (vedolizumab-3035) is a Phase 3 randomized, double-blind, placebo-controlled study designed to evaluate the use of vedolizumab as prophylaxis of intestinal aGvHD in participants who receive allo-HSCT as a treatment for a hematologic malignancy or myeloproliferative disorder from an unrelated donor.  Intestinal aGvHD is a serious complication characterized by inflammation of the GI tract, which can affect patients undergoing allo-HSCT, a common treatment for blood cancers.

Chinwe Ukomadu, M.D., Ph.D., Head, Gastroenterology Therapeutic Area Unit at Takeda has said, “these results have advanced our understanding of vedolizumab, currently indicated for IBD, in another critical GI inflammatory condition. Our Phase 3 study in the prevention of lower GI aGvHD is the latest example of Takeda’s commitment to advancing the science of vedolizumab, furthering the understanding of its mechanism of action, and exploring new ways to help patients.”

About 333 patients were enrolled in the study and the patients were randomly assigned in a 1:1 ratio to one of two treatment groups receiving either an intravenous infusion of vedolizumab 300 mg or placebo on days -1 (before allo-HSCT), and on days +13, +41, +69, +97, +125, and +153 following allo-HSCT, alongside a background GvHD prophylaxis regimen. The overall time of participation in the study was 12 months. No relevant differences in the safety profile between the vedolizumab and placebo arms were observed, and no new safety signals were identified. 
Vedolizumab is approved for treating adult patients with moderately to severely active UC and CD, who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFα)-antagonist. The further approval of Vedolizumab, is anticipated to improve the treatment scenario for the Intestinal aGvHD in patients undergoing Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT).