2022 FDA approval of new drug transcript

According to the statistics of PharmaSmart data, in 2022, the US FDA approved a total of 37 new molecular entities/new biological products. The total is down from last year, when the FDA approved 50 new drugs.

According to indications, antineoplastic drugs still dominate, with a total of 12 antineoplastic drugs, accounting for 32.4%, a slight decrease (35%) from 2021. In second place are drugs for inflammatory immune-related diseases, with a total of 6 drugs, three of which are for psoriasis, one for multiple sclerosis, one for eye drops, and one for atopic dermatitis.

Among the 37 drugs approved, 19 small molecule drugs (including compound preparations and contrast/imaging reagents) accounted for 51.4%, down about 10% from last year; Correspondingly, there were 18 kinds of biological preparations (including antibodies, peptide drugs, etc.), including 10 antibodies, 3 peptides, etc., accounting for a total of 48.6%. This data shows that at present, small molecule drugs still occupy a dominant position, but with the development of biotechnology, small molecule drugs are facing greater pressure.

Although the number of FDA-approved drugs in 2022 is down from the previous two years, there are still many bright spots this year:

Approved a variety of innovative therapies, including the world's first T-cell receptor therapy and one therapy for amyotrophic lateral sclerosis (ALS);

approved the first combination formulation for LAG-3, which is the third class of immune checkpoint inhibitors for tumor treatment after CTLA-4 and PD-1/PDL1;

1、Kimmtrak®(tebentafusp)

2022年1月26日，Kimmtrak®(tebentafusp)被批准用于治疗HLA-A*02:01阳性、不可切除或转移性葡萄膜黑色素瘤成年患者。

Tebentafusp's approval creates several firsts: as the first T-cell receptor therapy to receive regulatory approval from the FDA; The first bispecific T cell inducer to receive FDA regulatory approval for the treatment of solid tumors; and the first and only FDA-approved therapy for the treatment of unresectable or metastatic uveal melanoma.

Uveal melanoma is a devastating disease that usually results in the death of a patient within a year of metastasis. The approval of Tebentafusp represents a major paradigm shift in the treatment of metastatic uveal melanoma and offers hope for patients with this aggressive cancer for the first time.

Tebentafusp's approval is based on the results of the Phase III IMCgp100-202 clinical trial, published in the New England Journal of Medicine by Nathan et al. in September 2021. This randomized pivotal trial evaluated the overall survival of Tebentafusp in patients with previously untreated metastatic melanoma.

Nearly 400 patients were randomly assigned 2:1 to receive Tebentafusp and a control group (pembrolizumab, ipilimumab, or dacarbazine). Trial data show that tebentafusp as a first-line treatment shows an advantage in median overall survival.

For the first quarter ended March 31, 2022, Immunocore reported net income from KIMMTRAK and prior period products of $13.8 million.

2. "Frostbite" orphan drug: Relyvrio

On September 29, 2022, the FDA approved the drug Relyvrio (sodium phenylbutyrate and sodium taurate) developed by Amylyx Pharmaceuticals for the treatment of amyotrophic lateral sclerosis (ALS) in adults, based on favorable data from a small Phase 2 clinical trial (NCT03127514).

The mechanism by which this drug exerts a therapeutic effect on ALS patients is unknown. One explanation is that they can improve the health of the mitochondria and endoplasmic reticulum within cells, thereby delaying the death of nerve cells. Preclinical trials have shown that the synergistic effect of the combination of these two drugs can reduce the death of nerve cells due to oxidative stress by 90%. The FDA has granted Relyvrio orphan drug designation and priority review status.

A large Phase 3 study (NCT05021536) is underway to confirm the safety and efficacy of sodium phenylbutyrate and sodium taurine in this patient population.

In a multicenter, randomized, double-blind, placebo-controlled, parallel-group study, a total of 137 patients with ALS were randomly assigned to receive 2:1 sodium phenylbutyrate and sodium taurine (n=89) or placebo (n=48) for 24 weeks.

The data showed that ALS patients treated with sodium phenylbutyrate and sodium taurine experienced a slower decline in clinical assessment of daily function and a longer median overall survival than those treated with placebo.

In addition, follow-up of up to three years for all randomized participants showed a 44% lower risk of death in patients who received Relyvrio at the start of the trial compared with those who initially received placebo and switched to Relyvrio at the open-label stage (HR 0.56; 95% CI, 0.34 to 0.92). and median survival was 6.5 months longer (25.0 versus 18.5 months) in the group that received Relyvrio all the time compared to the group of patients initially treated with placebo.

The most common adverse effects of using Relyvrio were diarrhea, abdominal pain, nausea, and upper respiratory tract infections. In patients with diseases that interfere with the circulation of bile acids, there may be an increased risk of worsening of diarrhea. In addition, the product is high in salt, so patients who are sensitive to high salt intake should consider daily sodium intake.

3. The world's first drug targeting LAG-3: Opdualag

On March 18, 2022, the FDA approved nivolumab and relatlimab-rmbw (Opdualag, Bristol-Myers Squibb) for adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma. Opdualag is a fixed-dose combination of the LAG-3 blocking antibody relatlimab and the PD-1 blocking antibody nivolumab. The launch of Opdualag makes LAG-3 the third immune checkpoint for clinical application after PD-1/PD-L1 and CTLA-4.

A randomized (1:1), double-blind trial evaluating the efficacy of Opdualag (RELATIVITY-047 (NCT03470922)) was conducted in 714 patients with previously untreated metastatic or unresectable stage III or IV melanoma.

The trial excluded patients with active autoimmune disease, medical conditions requiring systemic treatment with moderate or high-dose corticosteroids or immunosuppressive drugs, uveal melanoma, and active or untreated brain or peripheral metastases.

Patients were randomized to receive either Opdualag (nivolumab 480 mg and relatlimab 160 mg) intravenously every 4 weeks, or nivolumab 480 mg intravenously every 4 weeks until disease progression or unacceptable toxicity.

The primary efficacy measure was progression-free survival (PFS), as determined by the blinded Independent Central Review (BICR) using RECIST v1.1. This trial showed a significant improvement in PFS by BICR compared with nivalumab (HR = 0.75; 95% confidence interval [CI]: 0.62, 0.92; P = 0.0055). The median PFS was 10.1 months (95% CI: 6.4, 15.7) in the opdualag group and 4.6 months (95% CI: 3.4, 5.6) in the nivolumab group.

An additional measure of efficacy outcomes is overall survival (OS). The final analysis of OS was not statistically significant (HR = 0.80; 95% CI: 0.64, 1.01), and median OS was not reached (NR) in the Opdualag group (95% CI: 34.2, NR) and 34.1 months (95% CI: 25.2, NR) in the nivolumab group.

The most common adverse effects of Opdualag (≥20%) were musculoskeletal pain, fatigue, rash, pruritus, and diarrhea. The most common laboratory abnormalities (≥20%) are decreased haemoglobin, lymphopenia, increased AST, increased ALT, and decreased sodium.

4, the world's first drug to slow down the process of type 1 diabetes: TZIELDTM (Teplizumab)

On November 17, 2022, the FDA approved Teplizumab (TZIELDTM) as the first and only immunomodulatory therapy for delaying the onset of stage 3 T1D in adults and children with stage 2 T1D and older aged 8 years and older. This is the biggest therapeutic breakthrough for the condition since the discovery of insulin 100 years ago.

Teplizumab was originally developed as a humanized anti-CD3 monoclonal antibody (mAb) developed at the University of Chicago and then further developed at MacroGenics. Eli Lilly licensed the drug from MacroGenics back in 2007. However, in a phase III clinical trial for type 1 diabetes mellitus (T1D), the phase III trial failed to meet the primary endpoint. Subsequently, the drug was acquired by Provention Biologics, which restarted development based on a subset analysis of the original trial.

A pivotal randomized, double-blind, event-driven, placebo-controlled trial (TN-10 study) of Teplizumab for diabetes prevention showed that Teplizumab can delay the progression of type I diabetes.

The most common side effects of Teplizumab include decreased levels of certain white blood cells, rashes, and headaches. The use of Teplizumab is accompanied by warnings and preventive measures, including pre-medication and monitoring of the symptoms of cytokine release syndrome; risk of serious infection; Decreased levels of white blood cells called lymphocytes; Risk of hypersensitivity reactions; All age-appropriate vaccinations are required before starting Teplizumab; and avoiding the use of live, inactivated and mRNA vaccines concomitantly with Tzield.

5. Four new drugs for rare diseases, including:

1)Pyrukynd

On February 17, 2022, the FDA approved the oral small molecule pyruvate kinase activator Pyrukynd. Pyrukynd is reviewed by the FDA based on a priority review, which has been awarded the "orphan drug" designation by the FDA, a drug used to treat rare diseases that affect fewer than 200,000 people.

2)Ztalmy®(ganaxolone)

On March 18, 2022, the FDA approved Ztalmy (ganaxolone) for the treatment of cyclin-dependent kinase-5 (CDKL5) deficiency (CDD)-related seizures in patients 2 years of age and older. It was the first treatment for CDD-related seizures and the first to treat CDD specifically.

3)Amvuttra

On June 13, 2022, the FDA approved Alnylam Pharmaceuticals' Amvuttra, a novel therapy for the treatment of hereditary transthyroxine (hATTR) amyloidosis polyneuropathy.

Amvuttra is classified as a gene silencing agent designed to inhibit the production of transthyroxine (TTR) protein in the liver, thereby reducing the level of TTR in the body and preventing amyloid buildup and organ damage. This approval follows positive results from a phase III study of HELIOS-A, in which patients treated with RNAi met all secondary endpoints at 18 months.

4)Xenpozyme

On August 31, 2022, the FDA approved Xenpozyme (Olipudase alfa) for intravenous use in children and adults with acid sphingomyelinase deficiency (ASMD), a rare genetic disorder that causes premature death. Xenpozyme is the first drug approved for the treatment of symptoms unrelated to the central nervous system in patients with ASMD.