5 Companies That Celebrated First Approvals in 2024

 

Madrigal Pharmaceuticals, X4 Pharmaceuticals and Day One Biopharmaceuticals secured their maiden approvals this year in metabolic dysfunction-associated steatohepatitis, WHIM syndrome and pediatric low-grade glioma. Geron Corporation and ImmunityBio also notched wins.

With a week still to go, the FDA has already issued more than 130 approvals this year. Some were label expansions or new approvals for blockbusters—Merck’s anti-PD1 therapy Keytruda appears on BioSpace’s 2024 FDA tracker multiple times—but more than 40 were for novel drugs, some of which are the first marketed drugs for their makers.

For companies like Madrigal Pharmaceuticals, X4 Pharmaceuticals and Day One Biopharmaceuticals, approvals in metabolic dysfunction-associated steatohepatitis (MASH), WHIM syndrome and pediatric low-grade glioma represent a maiden foray into the marketplace. For Geron Corporation, the approval of Rytelo for patients with lower- to intermediate-risk myelodysplastic syndromes, came after 34 years in business.

Notably, many of these first approvals are in indications with high unmet need. Madrigal’s Rezdiffra is the first-ever therapy for MASH, while X4’s Xolremdi is the first targeted treatment for WHIM syndrome, an ultrarare immunodeficiency disease affecting fewer than 1,000 people in the U.S. Others—such as ImmunityBio’s Anktiva for non-muscle invasive bladder cancer—are first in class.

In a previous interview with BioSpace, X4 CEO Paula Ragan spoke of the significance of transitioning to a commercial entity. “I think that’s a really important moment for any company; it’s really showing the lifelong commitment that we’re making to being here in perpetuity,” she said.

Here, BioSpace looks at five companies that secured their inaugural approvals in 2024.

Madrigal Pharmaceuticals

Rezdiffra

In one of the year’s most highly anticipated decisions, the FDA approved Madrigal’s Rezdiffra as the first treatment for MASH—a type of fatty liver disease that causes inflammation and destruction of liver cells. Rezdiffra, along with diet and exercise, is specifically indicated for patients with moderate to advanced liver fibrosis.

MASH, formerly known as nonalcoholic steatohepatitis (NASH), affects 5.3 out of every 1,000 people worldwide, according to a 2021 article published in MDPI. In the U.S., the disease accounts for 18% of all hepatocellular carcinoma cases.

Rezdiffra targets thyroid hormone receptor beta (THR-β), which helps maintain liver homeostasis. The FDA’s approval was based on results from the MAESTRO-NASH Phase III trial, in which Rezdiffra hit the two primary endpoints, significantly improving disease resolution and liver fibrosis. MASH resolved in 25.9% of patients who received an 80-mg dose of Rezdiffra and 29.9% of those taking 100 mg, with no worsening of fibrosis.

Experts who spoke with BioSpace prior to the approval said it could signal a sea change in the treatment of MASH, along with increasing the diagnosis of the disease.

X4 Pharmaceuticals

Xolremdi

In April, nearly two years after laying off 20% of its workforce and halting its oncology programs in an effort to extend its cash runway, X4 Pharmaceuticals won approval for Xolremdi as the first targeted treatment for WHIM syndrome.

According to the NIH, fewer than 1,000 people in the U.S. have been diagnosed with WHIM, which is an acronym for the four characteristics of the disease—warts, hypogammaglobulinemia, infections and myelokathexis. Hypogammaglobulinemia is a disorder caused by low antibody levels, while myelokathexis is a congenital disorder of the white blood cells.

An oral CXCR4 antagonist, Xolremdi is designed to mobilize white blood cells such as neutrophils, lymphocytes and monocytes from the bone marrow into the blood to improve immune deficiencies. In May 2023, X4 reported positive results from the Phase III 4WHIM trial, showing a 60% reduction in annualized infection rate compared to placebo; treated participants had less than one infection per year compared with 4.5 for the placebo group.

“It’s a privilege to gain an FDA approval of a drug, and I believe in rare disease,” Ragan told BioSpace in April. “It’s a responsibility to keep investing and being there for the patients as they need us.”

Day One Biopharmaceuticals

Ojemda

Also in April, Day One Biopharmaceuticals secured its first FDA approval, for Ojemda in BRAF-altered pediatric low-grade glioma (pLGG), the most common form of childhood brain tumor. With the approval, Day One received a rare pediatric disease priority review voucher.

Each year, approximately 15,000 children and adolescents are diagnosed with cancer in the U.S., per the CDC. Yet only 4% of federal funding of cancer research goes to pediatric oncology, according to the New York Times. Day One was founded “to bridge the gap between pediatric and adult [cancer] patients in terms of therapeutic options,” Day One CEO Jeremy Bender previously told BioSpace. The California-based company leverages the return on investment from an “all patients” approach to intentionally develop effective cancer therapies for kids.

“Ojemda is the first and only FDA-approved medicine for children with BRAF fusions or rearrangements, which are the most common molecular alteration in pLGG,” Bender said in a statement following the approval. “We are very proud that our first approved medicine addresses this serious and life-threatening disease of childhood and adolescence.”

Ojemda’s accelerated approval was partly based on the major efficacy outcome measure of overall response rate, defined as the proportion of patients with complete response, partial response or minor response by independent review based on Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO LGG).

Geron Corporation

Rytelo

Geron Corporation proved this year that perseverance pays off. In June, the company secured its first FDA approval, for Rytelo in lower- to intermediate-risk myelodysplastic syndromes (MDS), after 34 years in business.

Rytelo, an oligonucleotide telomerase inhibitor, also checks another novelty box as the first telomerase inhibitor to get the FDA’s greenlight.

MDS is a group of cancers in which blood cells in the bone marrow do not mature or become healthy blood cells. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In MDS, abnormal bone marrow cells often express the telomerase enzyme, which rebuilds telomeres and allows uncontrolled cell division. Rytelo works by inhibiting telomerase enzymatic activity, according to Geron.

The FDA’s approval of Rytelo was based on the Phase III IMerge trial, in which Rytelo had significantly higher rates of red blood cell transfusion independence (RBC-TI) over placebo for at least 24 weeks—28% in the treatment arm versus 3% on placebo. In these responders, RBC-TI was sustained for a median of 1.5 years.

In a statement, Rami Komrokji, vice chair of the Malignant Hematology department at Moffitt Cancer Center and a Merge investigator, called the approval “potentially practice-changing for us.”

ImmunityBio

Anktiva

Billionaire biotech entrepreneur Patrick Soon-Shiong scored his first FDA approval at ImmunityBio in April when the FDA greenlit Anktiva for non-muscle invasive bladder cancer (NMIBC).

A therapeutic fusion protein, Anktiva combines a mutant version of the IL-15 cytokine with an IL-15 receptor fusion protein. This structure enables the therapy to stimulate the proliferation of CD8+ T cells and natural killer cells while also activating CD4+ T helper cells, which boosts the division of memory killer T cells. It is the first IL-15 superagonist for NMIBC.

Anktiva is approved along with Bacillus Calmette-Guérin (BCG), a tuberculosis vaccine that also provokes an immune response in some bladder cancers, in BCG-unresponsive patients with carcinoma in situ. In the Phase II/III QUILT-3.032 study, maintenance treatment with Anktiva and BCG for up to 18 months led to a complete response rate of 62%, with duration of response exceeding 47 months at the November 2023 cut-off.

In a statement at the time, Soon-Shiong called the approval “an important milestone” not only for the company but also for NMIBC patients. “By orchestrating the innate and adaptive immune system and driving long-term complete remission, Anktiva has the potential to play a key role as the immunotherapy beyond checkpoints in multiple tumor types,” he said.

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