In 2022, the FDA's Center for Drug Evaluation and Research (CDER) approved 37 new drugs, including 22 new molecular entities (NMEs) and 15 biologics license applications (BLAs). In addition, the Center for Biologics Evaluation and Research (CBER) approved two vaccines, one cellular therapy, four gene therapies, and one microbiome therapy.
Figure 1. Novel FDA approvals since 1993. Source: reference [1]
Although the number of new drugs approved by the FDA has declined this year compared to previous years, the pace of innovation has not slowed. The percentage of NMEs approved by the FDA this year is at an all-time high. The percentage of "First-in-class" therapies has also ranked first in the past eight years.
So, in 2023, how many drugs will be approved? Which drugs have blockbuster potential? Recently, Evaluate released a report that makes predictions for the industry in 2023. The report states that there are 10 innovative therapies that could be approved in 2023 and are expected to become blockbusters in the future.
Figure 2. Source: Potential Blockbuster Drugs to be Approved in 2023, Source: Reference [2]
Blockbuster Drugs To Be Approved in 2023
Lecanemab (Eisai/Biogen)
Lecanemab, jointly developed by Eisai and Biogen, is a monoclonal antibody consisting of the humanized version of a mouse antibody, mAb158, that recognizes protofibrils and prevents amyloid beta deposition in animal models of Alzheimer's disease.
At the 15th Clinical Trials on Alzheimer's Disease Conference (CTAD) in late 2022, Eisai and Biogen reports full data from its successful phase 3 clinical trial of lecanemab. Lecanemab treatment met the primary endpoint and reduced cognitive decline, as measured by the Clinical Dementia Rating-Sum of Boxes (CDR-SB), compared with placebo at 18 months by 27% (change from baseline 1·21 for lecanemab vs 1·66 with placebo, p<0·001). This result represents an important breakthrough in a Phase 3 clinical trial of an Alzheimer's disease therapy targeting amyloid. On 6 January 2023, the FDA granted accelerated approval for the lecanemab (Leqembi), one of the first experimental dementia drugs to appear to slow the progression of cognitive decline.
Figure 3. People on lecanemab worsened more slowly on the CDR-SB, Soure: references [3]
SRP-9001 (Sarepta/ Roche)
SRP-9001, developed by Sarepta Therapeutics and Roche, is an investigational gene therapy for Duchenne muscular dystrophy (DMD) designed to deliver the drug to muscle tissue, which could promote the production of certain components of dystrophin.
At the 17th International Congress on Neuromuscular Diseases (ICNMD 2022), the companies jointly presented the results of multiple studies of SRP-9001, which confirmed the sustained efficacy of the therapy in patients with DMD. In November 2022, the FDA accepted and granted priority review to Sarepta Therapeutics' biologics license application (BLA) for SRP-9001. On 22 June 2023, the FDA approved SRP-9001 (delandistrogene moxeparvovec, ELEVIDYS) for the treatment of ambulatory patients with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene,which becomes the first approved gene therapy for DMD.
Intravitreal Pegcetacoplan (Apellis)
Pegcetacoplan, developed by Apellis Pharmaceuticals, is an intravitreal injectable 44 kDa PEGylated bicyclic peptide therapy targeting complement C3 for the treatment of geographic atrophy (GA) due to age-related macular degeneration (AMD).
Figure 4. Pegcetacoplan, source: company JP Morgan presentation.
The bicyclic peptides can combine the favourable properties of both major classes of both the monoclonal antibodies and the small molecule drugs and may bind as tightly and specifically as antibodies, while being small enough to diffuse into tissues. Due to their relatively rigid conformation, they can bind with high affinity and specificity to protein targets.
In a Phase 3 clinical trial, data at 24 months showed increased effects over time with intravitreal pegcetacoplan. On Feb. 17, the FDA approved SYFOVRE™ (pegcetacoplan injection) 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.
Biopharma PEG provides high-quality PEG raw materials and PEGylation reagents. These reagents are water soluble, monodisperse, biocompatible, and almost aggregation-free, making them ideal for bioconjugation or crosslinking of proteins, antibodies, peptides, oligonucleotides, or solid surfaces to other macromolecules, therapeutic compounds or other small molecules, and dyes.
Donanemab (Lilly)
Donanemab (LY3002813) is a humanized IgG1 monoclonal antibody targeted against an epitope at the N-terminal of a specific type of amyloid beta (Aβ) - pyroglutamate Aβ - which is found only in the brain amyloid plaques associated with Alzheimer's Disease (AD).
At the 15th Clinical Trials on Alzheimer's Disease Conference (CTAD) in late 2022, Lilly presented positive data for donanemab in a Phase 3 clinical trial. In a key secondary outcome, donanemab reduced brain amyloid levels vs. baseline by 65.2% compared with 17.0% for Aduhelm at 6 months. This data demonstrates the ability of donanemab to rapidly and effectively alter the biology of Alzheimer's disease in the early stages of treatment. Previously published Phase 2 clinical results showed that the therapy was able to mitigate the rate of cognitive and activities of daily living decline in patients with early stage Alzheimer's disease.
In August 2022, the FDA accepted the donanemab application for review, with Priority Review designation.
RSVPreF3 OA (GSK)
RSVPreF3 OA is an RSV vaccine candidate developed by GSK for the elderly, consisting of RSV prefusion F glycoprotein (RSVPreF3) in combination with a proprietary GSK adjuvant. This prefusion F glycoprotein is required for RSV virus entry into human cells. In a pivotal Phase 3 clinical trial, the investigational vaccine demonstrated an overall efficacy of 82.6% in subjects over 60 years of age and nearly 95% protection against severe RSV lower respiratory tract disease.
In November 2022, the FDA accepted a Biologics License Application and granted Priority Review for RSVPreF3 OA. On 3 May 2023, the FDA approved Arexvy (respiratory syncytial virus vaccine, adjuvanted) for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in individuals 60 years of age and older. This is the first RSV vaccine for older adults to be approved anywhere in the world.
Epcoritamab (Abbvie/ Genmab)
Epcoritamab is a CD20/CD3 bispecific antibody developed for subcutaneous administration through Genmab's proprietary DuoBody technology.
Figure 5. Epcoritamab Structure
Based on positive results from a Phase 1/2 clinical trial in relapsed/refractory large B-cell lymphoma (r/r LBCL), AbbVie and Genmab submitted a BLA to the FDA for epcoritamab. In this study, patients with relapsed or refractory LBCL who had previously received median third-line therapy had an overall response rate (ORR) of 63% and a complete response rate (CR) of 39%.
The FDA has granted priority review for the biologics license application (BLA) of epcoritamab. On May 19, 2023, the FDA granted accelerated approval to epcoritamab-bysp (Epkinly) for relapsed or refractory diffuse large B-cell lymphoma and high-grade B-cell lymphoma, which is the first bispecific antibody to be administered subcutaneously for the treatment of LBCL.
At the 2022 American Society of Hematology (ASH) Annual Meeting, the companies also presented results of positive trials of epcoritamab as a monotherapy or combination therapy for r/r follicular lymphoma (FL), untreated FL, r/r diffuse large B-cell lymphoma (DLBCL) and Richter's syndrome . The results showed that all combination therapies achieved an ORR of more than 80% in patients with different lymphomas. In the Richter's syndrome trial, epcoritamab as monotherapy achieved an ORR of 60% in patients, and it is reported that the drug has also filed an application in the EU for DLBCL.
Zuranolone (Biogen/ Sage)
In December 2022, Sage Therapeutics and Biogen jointly announced that they have completed the rolling submission of a New Drug Application (NDA) to the U.S. FDA for their investigational oral drug zuranolone (SAGE-217/BIIB125) for the treatment of major depressive disorder (MDD) and postpartum depression (PPD).
Figure 6. MOA of zuranolone
Zuranolone (SAGE-217) is a novel, synthetic, oral neuroactive steroid γ- aminobutyric acid A (GABAA) receptor positive allosteric modulator that targets brain networks responsible for functions such as mood, arousal, behavior, and cognition.
In patients with MDD, it may help to rapidly rebalance dysregulated neuronal networks to help restore brain function. This NDA submission includes data from the LANDSCAPE and NEST development programs. In clinical development programs to date, zuranolone has led to rapid and sustained improvement in depressive symptoms in patients, with generally good tolerability and a consistent safety profile. In a trial for PPD, improvement in depressive symptoms was seen as early as day 3 and continued through day 45 after zuranolone administration. On August 04, 2023, the FDA approved Zurzuvae (zuranolone), the first oral medication indicated to treat postpartum depression (PPD) in adults.
Mirikizumab (Lilly)
Mirikizumab is a humanized IgG4 monoclonal antibody that binds to the p19 subunit of IL-23 and blocks IL-23-mediated inflammatory responses. Mirikizumab is being developed in multiple clinical trials for the treatment of immune diseases, including psoriasis, ulcerative colitis (UC) and Crohn's disease.
Data from a Phase 3 clinical trial for UC published by Lilly in May 2022 showed that approximately half (49.9%) of patients receiving mirikizumab maintenance therapy achieved clinical remission at 1 year, while mirikizumab significantly improved patient urgency to defecate. Results from a previous phase 2 study showed that 75% of patients with moderate/severe UC treated with mirikizumab maintained symptomatic remission at two years. Lilly has submitted regulatory applications to the US FDA and EU EMA for mirikizumab in ulcerative colitis, with responses expected in 2023.
Etrasimod (Pfizer)
Etrasimod is a next-generation oral S1P modulator developed by Arena Pharmaceuticals, whose acquisition by Pfizer was completed in December 2021. Etrasimod is able to bind specifically to S1P receptors 1, 4, and 5 and may have improved efficacy/safety characteristics. It is being investigated in a range of immunoinflammatory diseases, including ulcerative colitis, Crohn's disease, atopic dermatitis, eosinophilic esophagitis, and pemphigus. In March 2022, Pfizer announced positive top-line results from two Phase 3 clinical trials of etrasimod for the treatment of moderate-to-severe UC. Both trials met their primary endpoints and showed significant improvements in all key secondary endpoints. The results from these two Phase 3 trials, as well as the long-term extension trial, will form the basis for a regulatory filing, which Pfizer had planned to initiate in 2022.
Sotatercept (Merck & Co)
Sotatercept is a potential first-in-class type IIA activin receptor (ActRIIA) fusion protein developed by Acceleron Pharma for the treatment of pulmonary arterial hypertension. In September 2021, Merck & Co. completed the acquisition of Acceleron Pharma, acquiring this innovative therapy.
Figure 7. Proposed Mechanism of Action for Sotatercept in Pulmonary Arterial Hypertension.
Sotatercept reduces activin-mediated signaling by fusing a modified extracellular domain of ActRIIA to the Fc-terminus of an antibody that blocks activin binding to the receptor on the cell membrane. In preclinical trials it reversed remodeling of the pulmonary artery wall and right ventricle. In October 2022, Merck & Co. announced positive data from a Phase 3 clinical trial of sotatercept in the treatment of pulmonary hypertension - in addition to meeting the primary endpoint, eight of the nine secondary endpoints demonstrated statistically significant improvements. After 24 weeks of treatment, sotatercept, in combination with stable background therapy, delivered a statistically significant and clinically meaningful improvement in patients' 6-minute walking distance (6MWD) compared to placebo. Previously, sotatercept was granted Breakthrough Therapy Designation by the FDA, the first investigational therapy for pulmonary arterial hypertension to receive Breakthrough Therapy Designation.
In the new year, we look forward to the release of these 10 potentially blockbuster therapies as scheduled.
References:
[1] 2022 FDA approvals, https://www.nature.com/articles/d41573-023-00001-3
[2] Evaluate Vantage 2023 Preview. Retrieved December 14, 2022, from https://www.evaluate.com/thought-leadership/vantage/evaluate-vantage-2023-preview
[3] 2022 Clarity AD CTAD Presentations. Retrieved November 30, 2022, from https://www.eisai.com/ir/library/presentations/pdf/e4523_221130.pdf
[4] Sarepta Therapeutics’ Investigational Gene Therapy SRP-9001 for Duchenne Muscular Dystrophy Demonstrates Significant Functional Improvements Across Multiple Studies, Retrieved July 7th, 2022, from https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-investigational-gene-therapy-srp-9001
[4] Apellis Announces 24-Month Results Showing Increased Effects Over Time with Pegcetacoplan in Phase 3 DERBY and OAKS Studies in Geographic Atrophy (GA). Retrieved August 24, 2022 from https://investors.apellis.com/news-releases/news-release-details/apellis-announces-24-month-results-showing-increased-effects
[5] Lilly Shares Positive Donanemab Data in First Active Comparator Study in Early Symptomatic Alzheimer's Disease. Retrieved December 1, 2022, from https://investor.lilly.com/news-releases/news-release-details/lilly-shares-positive-donanemab-data-first-active-comparator
[6] GSK’s respiratory syncytial virus older adult vaccine candidate granted Priority Review by US FDA. Retrieved November 2, 2022 from https://www.gsk.com/en-gb/media/press-releases/gsk-s-rsv-oa-vaccine-candidate-granted-priority-review-by-us-fda/
[7] U.S. FDA Accepts for Priority Review the Biologics License Application for Epcoritamab (DuoBody®-CD3xCD20) for the Treatment of Relapsed/Refractory Large B-Cell Lymphoma. Retrieved from https://news.abbvie.com/news/press-releases/us-fda-accepts-for-priority-review-biologics-license-application-for-epcoritamab-duobody-cd3xcd20-for-treatment-relapsedrefractory-large-b-cell-lymphoma.htm
[8] Sage Therapeutics and Biogen Complete Rolling Submission of New Drug Application for Zuranolone in the Treatment of Major Depressive Disorder and Postpartum Depression. Retrieved December 6, 2022, from https://investor.sagerx.com/news-releases/news-release-details/sage-therapeutics-and-biogen-complete-rolling-submission-new
[9] Fifty Percent of Patients with Ulcerative Colitis Treated with Mirikizumab Achieved Clinical Remission at One Year in Lilly's Pivotal Phase 3 Study. Retrieved May 24, 2022, from https://www.prnewswire.com/news-releases/fifty-percent-of-patients-with-ulcerative-colitis-treated-with-mirikizumab-achieved-clinical-remission-at-one-year-in-lillys-pivotal-phase-3-study-301552268.html
[10] Pfizer Announces Positive Top-line Results from Yearlong Phase 3 Trial of Etrasimod in Ulcerative Colitis, Underscoring Best-in-Class Potential. Retrieved March 29, 2022, from https://www.businesswire.com/news/home/20220329005198/en
Related Articles
Geographic Atrophy Treatments Under Investigation
Bispecific Antibodies - Current Status and Prospects
Complement Inhibitors as Therapeutic Agents
Monoclonal Antibodies: Limitations & Potential Improvement Strategies
Overview of PEG Linkers & Their Applications