Nature: FDA-approved new drug inventory and sales forecast in 2021

On January 4, Nature magazine took stock of the new drugs approved by the US FDA in 2021 and made sales forecasts

Despite the lingering effects of COVID-19, the number of FDA approvals last year was in line with recent trends

Number of new drugs approved by the FDA since 1993

In 2021, CDER approved a total of 50 new drugs, including the first KRAS inhibitor to treat cancer and the first anti-amyloid antibody to treat Alzheimer's disease

50 new drugs approved by CDER in 2021

Note: a: biological products; b: withdrawn from the market;

The FDA's Center for Biologics Evaluation and Research (CBER) also approved landmark mRNA vaccines and CAR-T cell products, and granted Emergency Use Authorization (EUA) for antibodies and rapidly developing oral antivirals to treat COVID-19

Cell Therapies and Vaccines Approved by CBER in 2021

Products to be granted EUA by FDA in 2021

In 2021, anticancer drug approvals will still dominate, accounting for 30% of the number of new drugs approved (15), and the 5-year average of anticancer drug approvals will be 28%

Areas where CDER approves new drugs

Among the new drugs approved by CDER in 2021, include the 100th antibody, two antibody-drug conjugates (ADCs), a bispecific antibody, a constrained peptide and two oligonucleotide drugs

CDER approval by drug type ("small molecule" includes all peptides up to 40 amino acids)

Analysts expect only eight of the new drugs approved by CDER to be blockbusters, according to the Clarivate Analytics database

2021 Approved Blockbuster 2027 Average Sales Forecast

Note: a: Average sales forecast in 2027; b: Sales forecast in 2021

A victory for vaccines

The CBER-approved vaccine is the star of the 2021 "approval show

BioNTech began development of the COVID-19 mRNA vaccine in January 2020 and entered into a partnership with Pfizer in March

Tozinameran also broke business records

Moderna's elasomeran (Spikevax) is a close second in both speed and profitability

FDA-approved new drug expected in 2022

Note: a: Breakthrough therapy designation; b: Astonishing sales by 2027 predicted by the Cortellis database

Pfizer's Prevnar 20, a 20-valent conjugate vaccine against S.

Analysts also predict that Vaxneuvance, Merck's newly approved 15-valent pneumococcal vaccine, will be a blockbuster

New breakthrough in cancer treatment

The approval of Amgen's KRAS-G12C inhibitor sotorasib is a milestone for the cancer community

Although the efficacy of sotorasib has been recognized in KRAS-G12C-mutant NSCLC patients, expectations have not been met

Other targeted KRAS therapies are under investigation
.
Mirati expects its KRAS-G12C inhibitor adagasib to be approved in 2022
.

The FDA approved Merck's first-in-class hypoxia-inducible factor-2α (HIF-2α) inhibitor for the treatment of tumors associated with VHL, a genetic disorder associated with vascular invasive tumors
.
Decades of research into the biology of VHL disease has shown that HIF-2α is a key driver of oxygen sensing -- paving the way for novel anti-angiogenic drugs, resulting in William Kaelin et al.
Nobel Prize
.

The approval of BMS' idecabtagene viceucel for multiple myeloma gives oncologists the first CAR-T cell therapy targeting BCMA
.
The other five CAR-T cell therapies approved by the FDA all target CD19
.
BCMA is expressed on the surface of B cells and has become a testing ground for antibodies, bispecifics, ADCs and cell therapies
.

Johnson & Johnson's BCMA-targeting CAR-T therapy ciltacabtagene autoleucel is under FDA review
.

GlaxoSmithKline's PD1 monoclonal antibody dostarlimabshi is the 100th antibody drug approved by the FDA
.
Thirty-five years ago, the FDA approved the first antibody in 1986
.
Today, the FDA approves about 10 antibody-based products each year
.

Dostarlimab is the 7th PD1/PDL1 mAb approved by the FDA, and while analysts predict Merck’s pembrolizumab sales will exceed $30 billion by 2027, they expect dostarlimumab sales to be only $2.
7 billion by 2025 billion dollars
.

Four other PD1/PDL1 antibodies are expected to be approved by the FDA in 2022
.
The FDA's Julia Beaver and Richard Pazdur recently wrote that checkpoint inhibitors have become a wildfire for drug development, marked by "the influx of commercial sponsors, clinical trials, and repeat development programs.

" They urged drug developers to collaborate better
.

BMS submitted the first BLA application for the checkpoint inhibitor relatlimab against LAG 3, and the FDA will make an approval decision in 2022
.

In 2021, the FDA approved two ADCs
.
ADC Therapeutics' loncastuximab tesirine is a CD19-targeting ADC for the treatment of B-cell lymphoma
.
Seagen/Genmab's tisotumab vedotin is a tissue factor-targeted cervical cancer ADC
.
The FDA currently has 11 ADCs approved, seven of which have been approved in the past three years
.
Clinical data from AstraZeneca's FDA-approved HER2-targeting ADC trastuzumab deruxtecan (DS-8201) in 2019 suggest that the novel ADC has better efficacy compared to antibodies and previously approved ADCs
.

Johnson & Johnson has approved a new drug, amivantamab, a bispecific antibody targeting EGFR and MET, for EGFR exon 20-mutated NSCLC, a type of cancer that is resistant to small-molecule EGFR inhibitors
.
Amivantamab is the third double antibody to market, and double antibody currently accounts for nearly 20% of the clinical-stage antibody pipeline
.

The FDA also approved Takeda's small-molecule kinase inhibitor mobocertinib, designed to selectively target exon 20-mutated EGFR
.

Controversy over new Alzheimer's drug

The FDA's approval of Biogen and Eisai's beta-amyloid-targeting antibody aducanumab was the most controversial approval decision of the year
.

On June 7, 2021, the US FDA resolutely approved the marketing of aducanumab based on the clinical surrogate endpoint (the level of amyloid plaques in the patient's brain) despite the objections of the expert committee
.
The FDA requires Biogen to confirm clinical efficacy of the antibody by 2030
.

Analysts still expect Biogen to generate $4.
1 billion in sales by 2027
.
But sales began to slow, and some treatment centers in the U.
S.
refused to prescribe the drug
.
Biogen initially priced aducanumab at $56,000 a year, but it has since halved
.
European regulators have refused to approve the antibody, and Japanese regulators appear set to refuse
.
The commercial success of the product will depend on whether the product is covered by the national health insurance plan (Medicare) for people 65 and older in the United States
.
A draft decision will be released in January next year
.

Two more anti-amyloid antibodies will come out in 2022
.
Biogen and partner Eisai have submitted a rolling BLA application for the anti-amyloid beta (Aβ) fibril antibody lecanemab (BAN2401) to the FDA through the accelerated approval pathway
.
Eli Lilly is also finalizing the submission of donanemab and hopes to have confirmatory trial evidence in 2023
.

Other significant approval events

With the approval of Novartis/Alnylam's inclisiran, a fourth siRNA-based drug is already on the market
.
The drug uses RNA interference to reduce the expression of the target
.

Inclisiran lowers LDL cholesterol by inhibiting PCSK9
.
The FDA approved two PCSK9-targeting antibodies in 2015 -- Regeneron/Sanofi's alirocumab and Amgen's evolocumab -- for a subset of patients at increased risk of cardiovascular disease, but neither product has yet reached critical mass pound bomb sales expectations
.
The ease of administration of Inclisiran may help it have better market performance
.
The mAbs are administered every 2-4 weeks, while inclisiran only needs to be administered twice a year
.

If the FDA approves Anlyam's vutrisiran in 2022, it would be the fifth approval for RNAi in as many years
.

With the first in class ANGPTL3 monoclonal antibody evinacumab, Regeneron has set a new first in the cardiovascular field
.
Regeneron genetically validated this target in atherosclerotic cardiovascular disease in 2017
.
Evinacumab is currently approved for the treatment of homozygous familial hypercholesterolemia (HoFH), a genetic disorder characterized by extremely high levels of LDL cholesterol
.
A phase III trial of evinacumab for the prevention of acute pancreatitis is ongoing
.

AstraZeneca/Amgen's tezepelumab is a first-in-class TSLP mAb for the treatment of severe asthma
.
TSLP is an IL-7-like cytokine that regulates multiple inflammatory cascades and can trigger allergic, eosinophilic, and other forms of inflammation associated with lung disease
.
Tezepelumab is the only biologic approved for the treatment of severe asthma without any phenotypic or biomarker limitations on its label
.
Analysts predict tezepelumab sales will reach $1.
4 billion by 2027
.

AstraZeneca's anfrolumab is the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in 10 years
.
Many patients with SLE have elevated levels of type I interferon, and Anifrolumab blocks the activity of these cytokines by binding to the type I interferon receptor
.

Apellis' pegcetacoplan, the first approved complement protein C3 inhibitor, is a synthetic restricted cyclic peptide for paroxysmal nocturnal hemoglobinuria, a rare and potentially fatal blood disorder
.

ChemoCentryx's avacopan, approved by the FDA in 2021 for ANCA-associated vasculitis, is the first approved complement 5a receptor antagonist
.

Despite the approval of COVID-19 vaccines, antibodies and antiviral drugs, the speed at which drug developers move under pressure is confirmed
.
But Takeda's maribavir offers a counterexample
.
Phase I data for this antiviral drug were first published in 1996
.
After surviving de-prioritization, outbound transfers, failed Phase III trials and two company acquisitions, the antiviral drug was finally approved this year for the treatment of cytomegalovirus (CMV) infection
.

First submission of new drug rejected by FDA

The FDA also rejected multiple marketing applications last year
.
Some of these may soon be resubmitted to the FDA for review
.
For example, Provention Bio is working to resubmit its CD3 mAb, teplizumab, for delaying type 1 diabetes in high-risk populations
.
Teplizumab was first used in clinical trials for transplant rejection in 1997 and has led a series of T-cell modulation therapies for autoimmune diseases
.

The new drug whose marketing application was rejected by the FDA for the first time

a: Approved by the end of 2021

Some new drugs rejected by the FDA have been discontinued
.
Pfizer/Lilly terminated development of the NGF-targeting mAb after the FDA issued a full response letter to tanezumab for the treatment of osteoarthritis pain
.
The FDA put once-promising anti-NGF drugs on hold in 2010 after data from a phase III study showed these painkillers could cause joint destruction
.