Top 10 Key Readouts in Q4 2024 Drug Development

The final quarter of 2024 will see the release of clinical data for several drug candidates, targeting indications such as obesity, depression, Alzheimer's disease, pain management, muscular atrophy, schizophrenia, and multiple sclerosis. These drugs encompass a variety of modalities, including small molecules, monoclonal antibodies, proteins, CAR-T cells, peptides, and a unique antibody-peptide conjugate.

Amgen's Peptibody Obesity Drug MariTIDE

Amgen's candidate MariTIDE (Maridebart Cafraglutide) stands out in the competitive field of obesity drug development due to its unique antibody-peptide conjugate (Peptibody) and novel mechanism of action. The MariTIDE molecule conjugates two GLP-1 receptor agonist peptides with an anti-GIP (Glucose-dependent Insulinotropic Peptide) antibody, forming a three-part antibody-peptide conjugate. The GLP-1 receptor agonists stimulate insulin secretion, while the anti-GIP antibody downregulates GIP secretion, working synergistically to achieve controlled weight loss.

MariTide molecular structure and schematic diagram of its mechanism of action. (Image source: Amgen)

The Phase II results for MariTIDE are expected before the end of the year, comparing and evaluating three selected doses of MariTIDE against a placebo over 52 weeks, in participants who are overweight or obese without diabetes (Cohort A) and those with type 2 diabetes (Cohort B). The industry is highly anticipating these results.

Novo Nordisk's New Blockbuster Weight Loss Drug CagriSema

Novo Nordisk will also reveal Phase III results for its weight loss candidate CagriSema by the end of this year. CagriSema combines Semaglutide (the active ingredient in Ozempic and Wegovy) with cagrilintide, an amylin analog. The upcoming Phase III study will test a combination of 2.4 mg Semaglutide and 2.4 mg cagrilintide. Additionally, Novo Nordisk initiated a new Phase III trial this summer to assess lower doses of CagriSema (1.0 mg Semaglutide/1.0 mg cagrilintide and 1.7 mg Semaglutide/1.7 mg cagrilintide), with results expected in 2026.

Bristol-Myers Squibb’s Cobenfy and AbbVie's Rival Drug Emraclidine

In September, Bristol-Myers Squibb’s Cobenfy became the first FDA-approved schizophrenia drug targeting brain muscarinic receptors. Meanwhile, AbbVie is actively developing a competing drug, Emraclidine, which it acquired through its $8.7 billion purchase of Cerevel Therapeutics. Like Cobenfy, Emraclidine is a selective M4 muscarinic receptor positive allosteric modulator, offering potential antipsychotic effects with fewer side effects than traditional dopamine-based therapies. Emraclidine's key clinical trial results in schizophrenia are expected by the end of this year.

Monoclonal Antibody Apitegromab for Spinal Muscular Atrophy

Scholar Rock is developing the monoclonal antibody Apitegromab, which blocks the precursor form of myostatin, a protein that inhibits muscle growth. Apitegromab is primarily intended for treating spinal muscular atrophy (SMA). A Phase III placebo-controlled study evaluating Apitegromab’s effects on non-ambulatory patients with Type 2 and Type 3 SMA is expected to release results this quarter.

Biohaven’s SMA Drug BHV-2000

Biohaven Pharmaceuticals is also developing a myostatin inhibitor, Taldefgrobep Alfa (BHV-2000), a fully human recombinant protein that inhibits both myostatin and activin A signaling. This unique mechanism may significantly reduce fat mass, increase lean mass, and improve metabolic parameters. Phase III results for Taldefgrobep Alfa are anticipated by the end of the year.

Vertex’s Non-Opioid Pain Medication Suzetrigine

Vertex Pharmaceuticals may achieve its next major growth milestone with the non-opioid pain medication Suzetrigine (VX-548). The FDA is currently reviewing its effectiveness in treating acute pain, with a decision expected by January 30, 2025. Before that, Vertex will release Phase II results for Suzetrigine in chronic pain, specifically targeting sciatica, this December. Suzetrigine's success could represent a breakthrough in the field of non-opioid pain management, where previous attempts have largely failed.

ALTO-100 Oral Depression Drug Phase II Results

Alto Neuroscience is set to release critical Phase IIb placebo-controlled results for its major depressive disorder (MDD) candidate ALTO-100. Previously known as NSI-189, this hippocampal neurogenesis stimulant is being developed for MDD, bipolar depression, PTSD, and potentially cognitive impairment and neurodegenerative diseases. The results will be a key milestone in ALTO-100's development.

Alzheimer's Disease Antibody AL002

Alector's Alzheimer's disease candidate AL002, developed in collaboration with AbbVie, will soon release Phase II placebo-controlled study results. AL002 is a humanized IgG1 monoclonal antibody targeting TREM2, a receptor linked to the genetic risk of sporadic Alzheimer's. By activating TREM2 signaling, AL002 enhances microglial cell function, potentially slowing the progression of dementia.

Cassava’s Controversial Alzheimer’s Drug Simufilam

Cassava Sciences' Alzheimer’s drug Simufilam, which has been embroiled in controversy, will complete a Phase III trial by December. The company recently faced SEC charges regarding misleading statements about Simufilam’s Phase II data. The trial's completion is being closely watched, with experts questioning the drug’s efficacy amid accusations of data manipulation.

CAR-T Therapy Anito-cel for Multiple Myeloma

ArCellx, in collaboration with Gilead, will present Phase II clinical results for its BMCA-targeting CAR-T therapy Anito-cel for multiple myeloma at the American Society of Hematology's annual meeting in early November. Anito-cel has received FDA fast track, orphan drug, and regenerative medicine advanced therapy designations. If successful, it could challenge BMS’s CAR-T therapy Abecma in the multiple myeloma space.

Reference

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• Alector Anno onces Completion of Enrollment in the INVOKE-2 Phase 2 Clinical Trial of AL002, a TREM2 Monoclonal Antibody, in Individuals With Early Alzheimer’s Disease. 
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