FDA Decisions Expected November 2024 - Prime Therapeutics
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FDA Decisions Expected
Drug pipeline for November 2024
October 14, 2024
Your monthly synopsis of new drugs expected to hit the market
At Prime Therapeutics (Prime), we have positioned ourselves to best prepare our clients to manage new drugs. Our clinical and trade relations teams keep a keen eye on drugs awaiting approval by the United States (U.S.) Food and Drug Administration (FDA).
Drug pipeline for November 2024
Nov. 9, 2024: zolbetuximab
Astellas is awaiting approval of zolbetuximab, a first-in-class Claudin (CLDN) 18.2-targeted monoclonal antibody, for the first-line treatment of adults with locally advanced unresectable or metastatic human HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN18.2-positive. CLDN18.2 is expressed in normal cells in the gastric mucosa and is retained in gastric and GEJ adenocarcinoma cells, making it a potential target for gastric cancer treatment. This is the second review of zolbetuximab, after the FDA returned a complete response letter (CRL) in January 2024 based on manufacturing facility inspection deficiencies; no clinical concerns were reported. In the SPOTLIGHT and GLOW clinical trials, zolbetuximab significantly improved the primary endpoint of progression-free survival (SPOTLIGHT, 11 versus 8.9 months [p=0.0024]; GLOW, (8.2 versus 6.8 months [p=0.0007]) and the secondary endpoint of overall survival (SPOTLIGHT, 18.21 versus 15.6 months [p=0.0075]; GLOW, 14.39 versus 12.16 months [p=0.0118]) when added to standard of care (SOC) chemotherapy regimens compared to chemotherapy alone. , Zolbetuximab received Orphan Drug designation and if approved, it will provide a new mechanism of action for treating gastric and GEJ adenocarcinoma.
Nov. 13, 2024: eladocagene exuparvovec (Upstaza)
PTC Therapeutics is seeking Accelerated Approval for Upstaza for the treatment of aromatic L-amino acid decarboxylase (AADC) deficiency, an ultra-rare, genetic, neurometabolic disorder characterized by intellectual disabilities, and life-long movement disorders and autonomic nervous system dysfunction. Onset of symptoms occur within the first few months of life. Upstaza is a recombinant adeno-associated virus serotype 2 (AAV2)-based gene therapy designed to increase AADC enzyme levels and restore dopamine production. It was granted Orphan Drug and Rare Pediatric Disease (RPD) designations as well as a Priority Review. Upstaza is administered as a one-time bilateral interputaminal (base of forebrain) infusion. In a clinical study, after a mean follow-up of 5.4 years, Upstaza led to a significant improvement in motor and cognitive functions reported at one year and persisted for at least five years. If approved, Upstaza will be the first treatment to target the underlying cause of AADC deficiency.
For more information, see the eladocagene exuparvovec (Upstaza) Deep Dive in the July 2024 edition of Prime Therapeutics’ Quarterly Drug Pipeline Quarterly Drug Pipeline: July 2024 - Prime Therapeutics - Portal
Nov. 16, 2024: obecabtagene autoleucel (obe-cel)
Obe-cel is an autologous CD19-directed chimeric antigen receptor T- cell (CAR T) therapy. Autolus submitted it to the FDA for the treatment of relapsed or refractory (R/R) adult B-cell acute lymphoblastic leukemia (ALL). Obe-cel is considered a Regenerative Medicine Advanced Therapy (RMAT) by the FDA. The product is designed with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve expansion/persistence. In the ongoing, open-label, single-arm, phase 1b/2 FELIX trial, after pre-conditioning with chemotherapy (cyclophosphamide and fludarabine), obe-cel was administered intravenously (IV) as a split dose on day 1 and day ten (± 2 days). Topline results revealed, at a median follow-up of 11 months (range, 0.9 to 30.6 months), 77% of patients achieved the primary endpoint of complete remission (CR) or CR with incomplete hematologic recovery (CRi). Grade ≥ 3 cytokine release syndrome occurred in 2.4% of patients and grade ≥ 3 immune effector cell associated neurotoxicity syndrome (ICANS) occurred in 7.1%. If approved, obe-cel will compete with the other CD19-directed CAR T- cell therapies, tisagenlecleucel (Kymriah) and brexucabtagene autoleucel (Tecartus), in the adult R/R B-cell ALL setting.
For more information, see the obecabtagene autoleucel Deep Dive in the July 2024 edition of Prime Therapeutics’ Quarterly Drug Pipeline Quarterly Drug Pipeline: July 2024 - Prime Therapeutics - Portal
Nov. 28, 2024: govorestat
The FDA granted a Priority Review for Applied Therapeutics’ oral, central nervous system (CNS) penetrating aldose reductase inhibitor (ARI) govorestat for the treatment of classic galatosemia. This rare, genetic disorder is characterized by an inability of the body to convert galactose to glucose, leading to accumulation the toxic metabolite galactitol in tissues and organs. In the placebo-controlled, phase 2/3, ACTION-Galactosemia Kids study, govorestat failed to meet the primary composite endpoint that consisted of four measures assessing language, expression, listening comprehension, and behavior. However, clinically meaningful improvements were seen regarding activities of daily living, behavior, cognition, adaptive skills and tremor. Govorestat was well tolerated. The FDA granted govorestat Fast Track, Orphan Drug and RPD designations to govorestat. While previously anticipated, the Agency informed Applied Therapeutics that an Advisory Committee meeting would no longer be required. If approved, govorestat will be the only medication available in the U.S. to treat classic galatosemia.
For more information, see the govorestat Deep Dive in the July 2024 edition of Prime Therapeutics’ Quarterly Drug Pipeline Quarterly Drug Pipeline: July 2024 - Prime Therapeutics - Portal
Nov. 29, 2024: acoramidis
Acoramidis is a tetrameric transthyretin (TTR) stabilizer by Bridgebio and AstraZeneca. The Orphan Drug is awaiting FDA approval for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). Acoramidis was evaluated in the double-blind, placebo-controlled, phase 3 ATTRibute-CM trial in adults with ATTR-CM and clinical heart failure. , It was administered orally twice daily. Published data reported that acoramidis did not significantly improve the first co-primary endpoint of the change in six-minute walking distance (6MWD) compared to placebo at 12 months. However, acoramidis led to a significant improvement over placebo (p<0.001) in the four-step primary hierarchical endpoint that included all-cause mortality (ACM), cardiovascular-related hospitalization (CVH), N-terminal pro–B-type natriuretic peptide (NT-proBNP) level, and 6MWD. If approved, acoramidis will be the second medication in the U.S. available to treat ATTR-CM and will directly compete with tafamidis agents ((Vyndaqel, Vyndamax).
For more information, see the acoramidis Deep Dive in the July 2024 edition of Prime Therapeutics’ Quarterly Drug Pipeline Quarterly Drug Pipeline: July 2024 - Prime Therapeutics - Portal
Nov. 29, 2024: zanidatamab
Jazz and Beigene are seeking Accelerated Approval for zanidatamab, a HER2-targeted bispecific antibody, for the treatment of previously treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC). FDA granted the agent a Priority Review as well as Breakthrough Therapy, Fast Track and Orphan Drug designations. Zanidatamab monotherapy, administered IV every two weeks, was evaluated in the single-arm, phase 2b HERIZON-BTC-01 trial. Among patients within situ hybridization [ISH]-positive and immunohistochemistry [IHC] 2+ or 3+ BTC, after a median follow-up of 21.9 months, the primary endpoint of confirmed objective response rate (ORR) was 41%. Secondary endpoint responses included a median duration of response (DOR) of 14.9 months, median overall survival (OS) of 15.5 months, and 12-month OS of 56.2%. Zanidatamab was generally well tolerated, with a manageable safety profile. If approved, zanidatamab will be the first HER2-targeted treatment specifically indicated for patients with HER2-positive locally advanced or metastatic BTC.
For more information, see the acoramidis Deep Dive in the July 2024 edition of Prime Therapeutics’ Quarterly Drug Pipeline Quarterly Drug Pipeline: July 2024 - Prime Therapeutics - Portal
References
All brand names are property of their respective owners.
At Prime Therapeutics (Prime), we have positioned ourselves to best prepare our clients to manage new drugs. Our clinical and trade relations teams keep a keen eye on drugs awaiting approval by the United States (U.S.) Food and Drug Administration (FDA).
Drug pipeline for November 2024
Nov. 9, 2024: zolbetuximab
Astellas is awaiting approval of zolbetuximab, a first-in-class Claudin (CLDN) 18.2-targeted monoclonal antibody, for the first-line treatment of adults with locally advanced unresectable or metastatic human HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN18.2-positive. CLDN18.2 is expressed in normal cells in the gastric mucosa and is retained in gastric and GEJ adenocarcinoma cells, making it a potential target for gastric cancer treatment. This is the second review of zolbetuximab, after the FDA returned a complete response letter (CRL) in January 2024 based on manufacturing facility inspection deficiencies; no clinical concerns were reported. In the SPOTLIGHT and GLOW clinical trials, zolbetuximab significantly improved the primary endpoint of progression-free survival (SPOTLIGHT, 11 versus 8.9 months [p=0.0024]; GLOW, (8.2 versus 6.8 months [p=0.0007]) and the secondary endpoint of overall survival (SPOTLIGHT, 18.21 versus 15.6 months [p=0.0075]; GLOW, 14.39 versus 12.16 months [p=0.0118]) when added to standard of care (SOC) chemotherapy regimens compared to chemotherapy alone. , Zolbetuximab received Orphan Drug designation and if approved, it will provide a new mechanism of action for treating gastric and GEJ adenocarcinoma.
Nov. 13, 2024: eladocagene exuparvovec (Upstaza)
PTC Therapeutics is seeking Accelerated Approval for Upstaza for the treatment of aromatic L-amino acid decarboxylase (AADC) deficiency, an ultra-rare, genetic, neurometabolic disorder characterized by intellectual disabilities, and life-long movement disorders and autonomic nervous system dysfunction. Onset of symptoms occur within the first few months of life. Upstaza is a recombinant adeno-associated virus serotype 2 (AAV2)-based gene therapy designed to increase AADC enzyme levels and restore dopamine production. It was granted Orphan Drug and Rare Pediatric Disease (RPD) designations as well as a Priority Review. Upstaza is administered as a one-time bilateral interputaminal (base of forebrain) infusion. In a clinical study, after a mean follow-up of 5.4 years, Upstaza led to a significant improvement in motor and cognitive functions reported at one year and persisted for at least five years. If approved, Upstaza will be the first treatment to target the underlying cause of AADC deficiency.
For more information, see the eladocagene exuparvovec (Upstaza) Deep Dive in the July 2024 edition of Prime Therapeutics’ Quarterly Drug Pipeline Quarterly Drug Pipeline: July 2024 - Prime Therapeutics - Portal
Nov. 16, 2024: obecabtagene autoleucel (obe-cel)
Obe-cel is an autologous CD19-directed chimeric antigen receptor T- cell (CAR T) therapy. Autolus submitted it to the FDA for the treatment of relapsed or refractory (R/R) adult B-cell acute lymphoblastic leukemia (ALL). Obe-cel is considered a Regenerative Medicine Advanced Therapy (RMAT) by the FDA. The product is designed with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve expansion/persistence. In the ongoing, open-label, single-arm, phase 1b/2 FELIX trial, after pre-conditioning with chemotherapy (cyclophosphamide and fludarabine), obe-cel was administered intravenously (IV) as a split dose on day 1 and day ten (± 2 days). Topline results revealed, at a median follow-up of 11 months (range, 0.9 to 30.6 months), 77% of patients achieved the primary endpoint of complete remission (CR) or CR with incomplete hematologic recovery (CRi). Grade ≥ 3 cytokine release syndrome occurred in 2.4% of patients and grade ≥ 3 immune effector cell associated neurotoxicity syndrome (ICANS) occurred in 7.1%. If approved, obe-cel will compete with the other CD19-directed CAR T- cell therapies, tisagenlecleucel (Kymriah) and brexucabtagene autoleucel (Tecartus), in the adult R/R B-cell ALL setting.
For more information, see the obecabtagene autoleucel Deep Dive in the July 2024 edition of Prime Therapeutics’ Quarterly Drug Pipeline Quarterly Drug Pipeline: July 2024 - Prime Therapeutics - Portal
Nov. 28, 2024: govorestat
The FDA granted a Priority Review for Applied Therapeutics’ oral, central nervous system (CNS) penetrating aldose reductase inhibitor (ARI) govorestat for the treatment of classic galatosemia. This rare, genetic disorder is characterized by an inability of the body to convert galactose to glucose, leading to accumulation the toxic metabolite galactitol in tissues and organs. In the placebo-controlled, phase 2/3, ACTION-Galactosemia Kids study, govorestat failed to meet the primary composite endpoint that consisted of four measures assessing language, expression, listening comprehension, and behavior. However, clinically meaningful improvements were seen regarding activities of daily living, behavior, cognition, adaptive skills and tremor. Govorestat was well tolerated. The FDA granted govorestat Fast Track, Orphan Drug and RPD designations to govorestat. While previously anticipated, the Agency informed Applied Therapeutics that an Advisory Committee meeting would no longer be required. If approved, govorestat will be the only medication available in the U.S. to treat classic galatosemia.
For more information, see the govorestat Deep Dive in the July 2024 edition of Prime Therapeutics’ Quarterly Drug Pipeline Quarterly Drug Pipeline: July 2024 - Prime Therapeutics - Portal
Nov. 29, 2024: acoramidis
Acoramidis is a tetrameric transthyretin (TTR) stabilizer by Bridgebio and AstraZeneca. The Orphan Drug is awaiting FDA approval for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). Acoramidis was evaluated in the double-blind, placebo-controlled, phase 3 ATTRibute-CM trial in adults with ATTR-CM and clinical heart failure. , It was administered orally twice daily. Published data reported that acoramidis did not significantly improve the first co-primary endpoint of the change in six-minute walking distance (6MWD) compared to placebo at 12 months. However, acoramidis led to a significant improvement over placebo (p<0.001) in the four-step primary hierarchical endpoint that included all-cause mortality (ACM), cardiovascular-related hospitalization (CVH), N-terminal pro–B-type natriuretic peptide (NT-proBNP) level, and 6MWD. If approved, acoramidis will be the second medication in the U.S. available to treat ATTR-CM and will directly compete with tafamidis agents ((Vyndaqel, Vyndamax).
For more information, see the acoramidis Deep Dive in the July 2024 edition of Prime Therapeutics’ Quarterly Drug Pipeline Quarterly Drug Pipeline: July 2024 - Prime Therapeutics - Portal
Nov. 29, 2024: zanidatamab
Jazz and Beigene are seeking Accelerated Approval for zanidatamab, a HER2-targeted bispecific antibody, for the treatment of previously treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC). FDA granted the agent a Priority Review as well as Breakthrough Therapy, Fast Track and Orphan Drug designations. Zanidatamab monotherapy, administered IV every two weeks, was evaluated in the single-arm, phase 2b HERIZON-BTC-01 trial. Among patients within situ hybridization [ISH]-positive and immunohistochemistry [IHC] 2+ or 3+ BTC, after a median follow-up of 21.9 months, the primary endpoint of confirmed objective response rate (ORR) was 41%. Secondary endpoint responses included a median duration of response (DOR) of 14.9 months, median overall survival (OS) of 15.5 months, and 12-month OS of 56.2%. Zanidatamab was generally well tolerated, with a manageable safety profile. If approved, zanidatamab will be the first HER2-targeted treatment specifically indicated for patients with HER2-positive locally advanced or metastatic BTC.
For more information, see the acoramidis Deep Dive in the July 2024 edition of Prime Therapeutics’ Quarterly Drug Pipeline Quarterly Drug Pipeline: July 2024 - Prime Therapeutics - Portal
References
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SPOTLIGHT trial: https://meetings.asco.org/abstracts-presentations/232477
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Upstaza trial: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822132/
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ATTR-CM trial: https://www.nejm.org/doi/full/10.1056/NEJMoa2305434
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Press release: https://meetings.asco.org/abstracts-presentations/234212
All brand names are property of their respective owners.