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10 Potential Blockbuster Drug Approvals in 2023
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

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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)

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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]

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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, with a PDUFA date set for May 29, 2023. If approved,
SRP-9001 would be the first 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).

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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. In July 2022, the FDA accepted and granted priority review to
the NDA for pegcetacoplan, with a PDUFA goal date set for February 26, 2023.
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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

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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, with a PDUFA date of 3 May, 2023. If approved, GSK's RSV
vaccine is expected to be the first vaccine to protect adults aged 60 years and older from
lower respiratory tract disease caused by RSV infection, the press release states. In
addition, European and Japanese regulators have accepted the marketing application for
this vaccine candidate.
Epcoritamab (Abbvie/ Genmab)
Epcoritamab is a CD20/CD3 bispecific antibody developed for subcutaneous
administration through Genmab's proprietary DuoBody technology.

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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 remission rate (ORR) of 63% and a complete
remission rate (CR) of 39%.
The FDA has granted priority review for the biologics license application (BLA)
of epcoritamab with a PDUFA date of May 21, 2023. If approved, epcoritamab would be
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

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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.

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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. Currently, zuranolone has been granted Fast Track
designation and Breakthrough Therapy designation by the FDA for the treatment of MDD
and Fast Track designation for the treatment of PPD.
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

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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.

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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

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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-inve
stigational-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-resul
ts-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-f
irst-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-r
eview-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-a

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pplication-for-epcoritamab-duobody-cd3xcd20-for-treatment-relapsedrefractory-large-b-cell-lymphoma.ht
m
[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-co
mplete-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
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