The "first" new drug approved by the FDA in 2022: involving TCR therapy, fecal bacterial therapy, bispecific antibodies, gene therapy, etc

According to public information, in 2022, the FDA approved 37 new drugs, including 22 new molecular entities and 15 biological products
.

Throughout these new drugs, at least 25 new drugs are of great significance in the history of drug review in the United States, involving 9 chemical drugs, 5 monoclonal antibodies, 3 bispecific antibodies, 2 gene therapies, 1 TCR therapy, ADC, peptides, etc
.
In terms of enterprises, large multinational pharmaceutical companies BMS occupy 3 models, Sanofi and Roche each occupy 2 models, and Eli Lilly, Novartis, Gilead, Johnson & Johnson and Boehringer Ingelheim each occupy 1 model
.

The first TCR therapy and fecal bacteria therapy came out

       1.
Kimmtrak（tebentafusp-tebn）

In January 2022, the FDA approved Kimmtrak (tebentafusp-tebn, IMCgp100) for the treatment of adult patients
with HLA-A*02:01 positive unresectable or metastatic uveal melanoma (mUM).

Kimmtrak active pharmaceutical ingredient tebentafusp is a novel bispecific protein formed by the fusion of soluble TCR with an anti-CD3 immune effector domain designed to specifically target gp100, a lineage antigen expressed in melanocyte and melanoma
.

Kimmtrak's approval created several firsts: (1) the first FDA-approved TCR therapy; (2) the first bispecific T cell junction approved by the FDA for the treatment of solid tumors; (3) The first and only FDA-approved therapy
for the treatment of unresectable or metastatic mUM.

       2.
Rebyota(fecalmicrobiota,live-jslm)

In November 2022, the FDA approved Rebyota (fecalmicrobiota, live-jslm) to reduce recurrence
after Clostridium difficile infection (CDI) in adults over 18 years of age.

Reybota is a single-dose enema made from a sample of gut bacteria taken from donor feces and does not contain any antibiotics, designed to help patients restore gut microflora and avoid reinfection
with CDI.
This approval makes Reybota the first FDA-approved fecal bacterial therapy
.

Cold agglutinin disease, pyruvate kinase deficiency and other diseases welcome the first treatment drugs

       1.
Enjaymo(sutimlimab-jome)

In February 2022, the FDA approved Enjaymo (Sutimlimab-jome) for the treatment of cold agglutinin disease (CAD).

Cold agglutinin disease hemolysis is driven
by the classical complement pathway.
Enjaymo is a monoclonal antibody that specifically targets the complement C1s protein, which plays a role
by blocking the function of the C1s protein in the classical complement pathway and inhibiting the hemolysis caused by complement protein activation.
Enjaymo is the first FDA-approved drug
for cold agglutinin disease.

       2.
Pyrukynd(mitapivat)

In February 2022, the FDA approved the PK (pyruvate kinase) activator Pyrukynd (mitapivat) for the treatment of adult patients
with PK deficiency and hemolytic anemia.

Pyruvate kinase deficiency is a rare genetic disorder that causes chronic hemolytic anemia
.
The reason behind this is that the PKLR gene mutation affects the pyruvate kinase activity of red blood cells, thereby reducing their ATP levels and allowing upstream metabolites to accumulate, resulting in energy loss
in red blood cells.

Pyrukynd is a "first-in-class" oral pyruvate kinase activator that is approved as the first disease-modifying therapy
for pyruvate kinase deficiency.

       3.
Vonjo（pacritinib）

In February 2022, the FDA approved Vonjo (pacritinib) for the treatment of patients
with myelofibrosis with severe thrombocytopenia.

Vonjo, the first drug specifically targeted for adult cytopenic myelofibrosis therapy, is a novel oral kinase inhibitor that is specific for JAK2 and IRAK1, aids in signaling and growth of a variety of cytokines, and has important effects
on hematopoietic function.

       4.
Ztalmy（ganaxolone）

In March 2022, the FDA approved Ztalmy (ganaxolone, ganetholone) oral suspension for the treatment of seizures
associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency (CDD) in patients 2 years of age and older.

CDKL5 deficiency (CDD) is a severe and rare form of inherited epilepsy characterized by early onset, difficult seizure control, and severe impairment of neurodevelopment
.
CDD is caused
by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene located on the X chromosome.

Ztalmy, the first drug approved by the FDA specifically for the treatment of CDD, is a neuroactive steroid that acts
as a positive allosteric modulator of GABAA receptors.

       5.
Vivjoa(oteseconazole）

In April 2022, the FDA approved the oral azole antifungal drug Vivjoa to reduce the recurrence rate
of recurrent vulvovaginal candidiasis (RVVC) in women without reproductive potential.

RVVC, also known as chronic yeast infection, is usually defined as acute episodes of symptomatic yeast infection occurring more than 3 times a year, the main symptoms include vaginal itching, burning, irritation, and inflammation, and some patients also have abnormal vaginal discharge and painful
sexual intercourse or urination.

Vivjoa, the first FDA-approved RVVC therapy, is an orally administered fungal CYP51 inhibitor
.
Compared to currently available antifungal drugs, Vivjoa has higher selectivity, fewer side effects, and higher efficacy
.

       6.
Xenpozyme(olipudase alfa)

In August 2022, the FDA approved Xenpozyme for the treatment of non-central nervous system disorders
in children and adult patients with acid sphingomyelipase deficiency (ASMD).

Acid sphingomyelinase deficiency (ASMD) is a rare, progressive genetic disorder in which patients fail to break down sphingomyelin, which accumulates in the liver, spleen, lungs and brain due to mutations in genes encoding sphingomyelin-metabolizing enzymes, and signs and symptoms include enlarged spleen or liver, difficulty breathing, lung infections, unusual bruising or bleeding, resulting in pain, vomiting, feeding difficulties and falls, among other manifestations
.

Xenpozyme is the first FDA-approved drug for the treatment of ASMD for non-central nervous system manifestations

7.
Terlivaz

In September 2022, the FDA approved Terlivaz for the treatment of adult hepatorenal syndrome with rapidly deteriorating renal function
.

Hepatorenal syndrome (HRS) is an acute and potentially life-threatening condition that is common in people with
advanced liver disease.
Patients with haemodynamic abnormalities that eventually lead to visceral and systemic vasodilation, which may trigger portal hypertension and renal vasoconstriction
.
Insufficient cardiac output due to systolic dysfunction increases the risk of
renal failure.
Liver transplantation is currently the only cure for HRS patients, but liver transplantation is not available, and patients often have too late to undergo liver transplantation
.

Terlivaz, the world's first FDA-approved drug to improve kidney function in adults with HRS, is a synthetic analogue of vasopressin that has vasoconstrictive effects, reduces hepatic blood flow and portal vein pressure, and increases effective arterial blood volume and mean arterial pressure (MAP)
at the same time.
The drug has about 2 times more selectivity
for vasopressin V1 receptors than V2 receptors.

       8.
Skysona（elivaldogene autotemcel）

In September 2022, the FDA accelerated approval of Skysona for the marketing of slowing the progression of
neurological dysfunction in boys aged 4-17 years with early active cerebral adrenal leukodystrophy (CALD).

CALD is a progressive and irreversible neurodegenerative disease caused by mutations in the ABCD1 gene that affects the production of adrenal leukotrophin (ALDP) and subsequently leads to toxic accumulation of very long chain fatty acids (VLCFAs), mainly in the adrenal glands and white matter and spinal cord
.

Skysona is the first and only one-off gene therapy to be approved by regulatory approval for the treatment of CALD, utilizing Lenti-D lentiviral vector (LVV) for in vitro transduction to add a functional copy of the ABCD1 gene to the patient's
own hematopoietic stem cells (HSCs).
The addition of the functional ABCD1 gene enables patients to produce the ALD protein (ALDP), which is thought to contribute to the breakdown
of VLCFA.

       9.
Tzield（teplizumab）

In November 2022, the FDA approved Tzield for use to delay the progression of stage 3 type
1 diabetes in adults with stage 2 diabetes and children over 8 years of age.

Tzield, the world's first drug to delay the progression of type 1 diabetes, is an anti-CD3 monoclonal antibody that protects islet β cells from destruction by binding to CD3 on the surface of certain immune system cells (effector T cells) and inhibiting T cell attacks on islet β cells
.
Tzield may delay the progression of the disease to stage
3 in people with type 1 diabetes by inactivating immune cells that attack insulin-secreting cells while increasing the proportion of cells that help regulate the immune response.

Multiple targets welcome new drugs to market

       1.
Opdualag（Relatlimab/nivolumab）

In March 2022, the FDA approved Opdualag for the treatment of adults and children
over the age of 12 with unresectable or metastatic melanoma.
Opdualag is a dual immunotherapy Relatlimab + Nivolumab fixed-dose combination drug developed by BMS, of which Relatlimab is a monoclonal antibody drug targeting lymphocyte activation gene 3 (LAG3), and Nivolumab is BMS's blockbuster product, the world's first approved PD-1 monoclonal antibody Opdivo
.

Opdualag is the first FDA-approved combination therapy with LAG3 monoclonal antibody, and published Phase 3 clinical trials have shown that median progression-free survival of Opdualag can be more than
doubled compared with nivolumab monotherapy.

       2.
Camzyos（Mavacamten）

In April 2022, the FDA approved Camzyos for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy of Class II-III by the New York Heart Association (NYHA) to improve functional capacity and symptoms
.
Obstructive hypertrophic cardiomyopathy is a condition
in which the heart muscle thickens and weakens its ability to pump blood.

Camzyos, the first drug to treat obstructive hypertrophic cardiomyopathy, is a novel small-molecule allosteric modulator of myosin, which can improve myocardial hypersystolic function in HCM patients by inhibiting calcium-myosin binding and preventing bridge formation, thereby improving myocardial diastolic function and clinical outcomes
.

       3.
Mounjaro(tirzepatide）

In October 2022, the FDA approved Mounjaro as an adjunct diet and exercise for improving glycemic control
in adults with type 2 diabetes mellitus (T2D).

Mounjaro is the first and only GIP/GLP-1 receptor agonist approved by the FDA and the first new hypoglycemic drug
approved for marketing in the past 10 years.
The results of the global multi-center phase 3 clinical trial SURPASS showed that compared with all control groups, the Mounjaro group achieved blood glucose reduction and significant weight loss
.

       4.
Spevijo（spesolimab）

In September 2022, the FDA approved Spesolimab for the treatment of generalized pustular psoriasis (GPP) episodes
in adults.
GPP is a rare, heterogeneous, life-threatening neutrophilic skin disease that differs from
plaque psoriasis.
GPP is caused by the accumulation of neutrophils (a type of white blood cell) in the skin, causing widespread eruptions of painful sterile pustules
throughout the body.

Spevigo is a humanized monoclonal antibody
targeting IL-36R.
The IL-36 pathway is a signaling pathway within the immune system that has been shown to be associated with
the pathogenesis of various autoimmune diseases such as GPP.
This approval makes Spevigo the first GPP therapy approved by the FDA and the first IL-36 monoclonal antibody
approved worldwide.

       5.
Sotyktu（deucravacitinib）

In September 2022, the FDA approved Sotyktu for the treatment of patients
with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Sotyktu (deuterated colesitinib) is the only approved TYK2 inhibitor in the world, which selectively binds to the TYK2 protein regulatory domain to make TYK2 in an inactive state, thereby selectively inhibiting the activity of TYK2 and avoiding the inhibition of proteins JAK1, JAK2 or JAK3, thereby avoiding related cardiovascular events or venous thromboembolic adverse events
.

The results of two pivotal Phase 3 clinical trials based on this were 58.
7% and 53.
6% in the deuterium colesicitinib group with PASI 75 (at least 75% improvement in psoriasis area and severity index) in the two trials compared with placebo and appremilaster at week 16, compared with 12.
7% and 9.
4%, 35.
1% and 40.
2%
in the placebo and appremilaster groups, respectively.

       6.
Tecvayli(teclistamab)

In November 2022, the FDA approved Tecvayli for the treatment of adult patients
with relapsed or refractory (R/R) multiple myeloma (MM) who had previously received 4 or more lines of therapy (including proteasome inhibitors, immunomodulators, anti-CD38 monoclonal antibodies).

Tecvayli is the first BCMAxCD3-targeted bispecific antibody approved worldwide and the first bispecific antibody
approved for the treatment of MM.
The drug is a ready-to-use product that is administered
by subcutaneous injection.
The results of its approved pivotal Phase 1/2 MajesTEC-1 study showed that the ORR of Tecvayli treatment was 61.
8%, with 28.
2% of patients achieving complete response (CR) or better response
.
In patients in remission, the median time from treatment to first confirmed response was 1.
2 months (range 0.
2 to 5.
5 months).

The median follow-up was 7.
4 months, and the median duration of response (DOR) had not been reached
.

       7.
Elahere(mirvetuximab soravtansine-gynx)

In November 2022, ImmunoGen announced that it had approved Elahere for the treatment of adult patients with platinum-resistant ovarian epithelial carcinoma, fallopian tube cancer, or primary peritoneal cancer who were folate receptor α (FRα)-positive and had previously received a 1-3 line of systemic therapy
.

Elahere is the first FRα-targeted antibody conjugate (ADC) approved worldwide, including FRα-binding antibodies, cleavable linkers, and Medenlignomaloid DM4, a potent tubulin-targeting agent
.
The results of the pivotal SORAYA trial showed that the investigator-evaluated ORR was 31.
7%, including 5 CRs, and the median DOR was 6.
9 months
.

       8.
Lunsumio (mosunetuzumab-axgb)

In December 2022, the FDA approved Lunsumio for the treatment of patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of
systemic therapy.

Lunsumio is the first FDA-approved CD20xCD3 T cell binding bispecific antibody designed to target CD20 on the surface of B cells and CD3
on the surface of T cells.
This dual targeting activates and redirects the patient's existing T cells, which participate in and eliminate target B cells by releasing cytotoxic proteins into B cells
.

Data from the approved Phase 2 GO29781 study showed that the ORR reached 80% in patients treated with Lunsumio, most of whom had a duration of remission of at least 18 months
.
The median duration of response for responders was almost 2 years (22.
8 months).

Complete remission
was achieved in 60% of patients.

A variety of diseases welcome new therapies, involving drug types and targets

       1.
Vabysmo（faricimab-svoa）

In January 2022, the FDA approved Vabysmo for the treatment of wet age-related macular degeneration (AMD) and diabetic macular edema (DME).

Faricimab is the first ophthalmic dual antibody approved worldwide to target and inhibit two disease pathways
associated with many vision-threatening retinal diseases by neutralizing angiopoietin-2 (ANG-2) and vascular endothelial growth factor-A (VEGF-A).
Faricimab can reduce the frequency of ocular injections and improve long-term vision outcomes
compared with anti-VEGF therapy alone.

       2.
Pluvicto（177Lu-PSMA-617）

In March 2022, the FDA approved the marketing of targeted radiotherapy Pluvicto for the treatment of patients
with prostate-specific membrane antigen (PSMA)-positive, metastatic castration-resistant prostate cancer (mCRPC).

Pluvicto is the first FDA-approved targeted radioligand therapy for the treatment of these mCRPC patients, a combination of targeted ligand and radioisotope therapy that targets PSMA-positive cells and causes DNA damage to kill tumor cells
through radioisotopes.

It was approved based on the results of a Phase 3 clinical trial showing a 38% lower risk of death in patients treated with Pluvicto compared with standard care (SOC); The overall response rate was 30% in the Pluvicto group and only 2%
in the control group.

       3.
Vtama(tapinarof)

In May 2022, the FDA approved Vtama (tapinarof) cream for the topical treatment of plaque psoriasis in adults, making Vtama the first steroid-free topical drug
of its kind to be approved by the FDA.

The active ingredient of Vtama, tapinarof, is an aromatic hydrocarbon receptor modulator, as a non-hormonal small molecule drug with good skin permeability, by regulating the function of aromatic hydrocarbon receptors, it can inhibit IL-17-mediated inflammatory response (IL-17 signaling pathway is a "key target" for the treatment of psoriasis).

       4.
Hemgenix (etranacogene dezaparvovec)

In November 2022, the FDA approved Hemgenix for the treatment of hemophilia B
in age 18 and older.

Hemgenix is the first gene therapy approved by FDA to treat adult patients with hemophilia B, it is a gene therapy based on AAV5 vector, equipped with coagulation factor IX (FIX) gene variant, administered intravenously, after administration the gene can express FIX coagulation factor in the liver, secretion into the blood to play coagulation function, so as to achieve the purpose of treatment, theoretically a single administration long-term effective
.

       5.
Sunlenca（lenacapavir）

In December 2022, the FDA approved Sunlenca (lenacapavir) in combination with other antiretroviral drugs for the treatment of multidrug-resistant adult patients
with human immunodeficiency virus (HIV) infection.

Sunlenca, a first-of-its-kind, long-acting HIV capsid inhibitor, offers a new, biannual treatment option
for adult patients with HIV who are not adequately controlled by current treatment regimens.
The data from the Phase 2/3 CAPELLA clinical trial on which it was approved showed that 88% (n=21/24) of patients treated with Sunlenca achieved virus reduction, compared with only 17% (n=2/12) of patients treated with placebo
.
After 26 weeks of Sunlenca plus other antiretroviral drugs, 81 percent of participants in the first group achieved HIV RNA suppression, in which HIV levels were low enough to be considered undetectable
.

       6.
Briumvi(ublituximab)

In December 2022, the FDA approved Briumvi for the treatment of relapsing multiple sclerosis (RMS), including clinically isolated syndrome, relapse-remitting disease, and active secondary progressive disease
in adults.

Briumvi is the first and only anti-CD20 monoclonal antibody approved for the treatment of RMS, targeting unique epitopes
on CD20 antigens expressed by B cells.
When Briumvi binds to B cells, it can trigger a series of immune responses such as antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), thereby destroying B cells
.