Since the beginning of this year, the US FDA has approved a total of 45 innovative drugs, compared with 44 in the same period last year and 53 in the whole year of last year. In November, the FDA approved 3 models (Livtencity, Voxzogo, Besremi), of which:

-Takeda Pharmaceutical's antiviral drug Livtencity is the first drug used to treat refractory CMV infections in transplant recipients;

——BioMarin's C-type natriuretic peptide (CNP) analogue Voxzogo is the first drug to treat achondroplasia in children;

——Taiwan Yaohua Pharmaceutical Company's innovative single-PEG long-acting interferon Besremi is the first interferon product specifically for the treatment of polycythemia vera (PV).

Entering December, a number of drugs will usher in an important review decision by the FDA

Several of the blockbuster drugs are as follows:

Enterprise: Merck

Drug: Keytruda

Estimated time of approval: December 4, 2021

Indications: Adjuvant treatment of adult and pediatric patients (12 years and older) with stage IIB or IIC melanoma who have undergone complete resection

The US FDA accepted Merck's Keytruda's supplementary biological product license application (sBLA) in early August of this year. At present, the FDA has granted priority review to the sBLA and designated the Prescription Drug User Fees Act (PDUFA) as the target date of December 4, 2021.

It is reported that the sBLA is mainly based on data from the Phase 3 KEYNOTE-716 trial. The data from the clinical trial KEYNOTE-716 was released earlier this month at the Society for Melanoma Research (SMR) 2021 conference.

KEYNOTE-716 is a multicenter, randomized, double-blind phase 3 clinical trial that is comparing the efficacy and safety of Keytruda and placebo in adjuvant treatment of stage IIB or IIC melanoma after complete resection of adult and pediatric (12 years and older) patients sex. The primary endpoint of the trial is recurrence-free survival (RFS).

In the second interim analysis (IA2) of the protocol, Keytruda adjuvant therapy continued to show clinically significant improvement in RFS compared with placebo, and the risk of disease recurrence or death was reduced by 39% (HR=0.61[95%CI: 0.45 -0.82]). The KEYNOTE-716 trial reached the primary endpoint of RFS in the first interim analysis (HR=0.65[95%CI:0.46-0.92]; p=0.00658), therefore, no statistical test was performed in IA2. No new safety signals were observed.

At IA2, 14.8% (n=72/487) of patients treated with Keytruda relapsed or died, while 23.5% of patients treated with placebo (n=115/489). At the time of this analysis, the median RFS of the two groups did not reach. The remote recurrence rate of patients in the placebo group (12.3%[n=60/489]) was twice that of patients in the Keytruda group (6.4%[n=31/487]).

At the time of IA2, Keytruda's security features were consistent with previous reports. Treatment-related adverse events occurred in 82.8% (n=400/483) and 63.4% (n=308/486) in the Keytruda treatment group and placebo group, respectively, and 17.0% (n=82/483) and 4.3% (n =21/486) patients had grade 3-4 adverse events, 10.1% (n=49/483) and 1.2% (n=6/486) of patients had grade 3-4 immune-mediated adverse events and Infusion reaction.

Enterprise: Amgen

Drug: Otezla (apremilast, Apomilast)

Estimated time of approval: December 19, 2021

Indications: Treatment of adult patients with mild to moderate plaque psoriasis

Otezla is an oral small molecule phosphodiesterase 4 (PDE4) inhibitor with specificity to cyclic adenosine monophosphate (cAMP). It can increase the intracellular cyclic adenosine monophosphate (cAMP) content by inhibiting PDE4, thereby Increase anti-inflammatory cytokines and down-regulate inflammation. In August 2019, Amgen acquired from Xinji and BMS at a price of $13.4 billion. The drug continues to maintain its leading position in the first-line psoriasis market. Last year, Amgen's global sales were close to 2.2 billion U.S. dollars. It is estimated that Otezla's sales revenue may exceed US$3 billion by 2023.

In 2014, Otezla was approved for listing in the United States. Currently, it has been approved for three indications in the United States, including adult active psoriatic arthritis (PsA), moderate to severe plaque psoriasis, and Behçet’s synthesis Sign (Behcet) related oral ulcers. On August 16 this year, Amgen Otezla (apremilast, Apomilast tablets) was approved for listing in China for psoriasis.

In September of this year, Amgen won a patent dispute with Sandoz and Zydus against the blockbuster psoriasis drug Otezla. United States District Judge Michael Shipp of Trenton, New Jersey, stated that the generic drugs proposed by Sandoz and Zydus both infringed three patents held by Amgen. The court ruled in favor of Amgen, preventing Sandoz and Zydus from manufacturing, using, selling, offering for sale or importing any version of Otezla before the COM patent (US Patent No. 7,427,638) expires in February 2028. Generic drugs.

Bristol-Myers Squibb’s TYK2 inhibitor deucvacitinib is a competing drug for Otezla. In November last year, in a phase 3 POETYK PSO-1 key clinical trial for patients with moderate to severe plaque psoriasis, Bristol-Myers Squibb The efficacy of the TYK2 inhibitor deucravacitinib exceeds that of Otezla. Research data shows that compared with Otezla, the proportion of patients who reached PASI 75 and sPGA 0/1 after deucravacitinib treatment at the 16th week is better than Otezla. In this study, the overall safety results of deucravacitinib are consistent with the results of the previously announced phase II study.

Enterprise: Bristol-Myers Squibb

Drug name: Orencia (abatacept, Abatacept)

Estimated time of approval: December 23

Indications: For patients 6 years and older who have received unrelated donor hematopoietic stem cell transplantation (URD-HSCT) to prevent moderate to severe acute graft-versus-host disease (aGvHD)

Abatacept is the first approved T cell selective costimulatory immunomodulator in the field of rheumatoid arthritis in the world. It binds to CD80 and CD86 on antigen presenting cells to block CD28 on T cells. Interaction, inhibit the activation of T cells. Activated T-cells are believed to be related to a variety of inflammatory diseases, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), juvenile idiopathic arthritis (JIA) and so on. Full activation of T-cells requires at least two signals from antigen-presenting cells. The interaction of CD28 on T-cells and CD80 or CD86 on antigen-presenting cells is a key step in costimulatory signal transduction.

In the United States, the drug has been approved for 3 indications since it was launched in 2005: (1) for the treatment of moderate to severely active rheumatoid arthritis (RA) adult patients; (2) for the treatment of 2 years old and The above moderate to severe active polyarticular juvenile idiopathic arthritis (pJIA) patients; (3) for the treatment of adult patients with active psoriatic arthritis (PsA). In terms of medication, it is not recommended to use Orencia and other effective immunosuppressants at the same time, such as: biological disease modified anti-rheumatic drugs (bDMARD), JAK inhibitors.

In Mainland China, Abatacept injection was developed in cooperation with Simcere and Bristol-Myers Squibb. On August 9, 2020, Abatacept held a launch event, marking the official entry of the product into commercial circulation in mainland China.

Reference source: Biotech Stocks Facing FDA Decision In December 2021