New drug series: 2017 FDA approves new drugs and synthetic route analysis

- Jul 17, 2018-

Rucaparib (Rubraca)

On December 19, 2016, the US Food and Drug Administration (FDA) accelerated the approval of Rucaparib (trade name Rubaraca, manufactured by ClovisOncology) for advanced ovarian cancer associated with BRCA gene mutations after two or more lines of chemotherapy.

The approval is based on the results of two clinical studies. Participants with advanced ovarian cancer, positive for BRCA mutation detection, and two or more lines of chemotherapy. The objective response rate for Rucaparib (trade name Rubaraca) treatment was 54%; in platinum-sensitive patients, the objective response rate for treatment was 66%; in patients who were not sensitive to platinum, the objective response rate for treatment was 25 %; In patients with platinum-refractory, the objective response rate for treatment was 0%; the objective response rate for treatment did not differ between patients with BRCA1 and BRCA2 mutations. The median response duration was 9.2 months.

>>>> Drug molecular information:

Common name: Rucaparib

Alias: AG-014699, PF-0136738

Chemical formula: C19H18FN3O Molecular weight: 421.36

English chemical name: 8-Fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one

CAS No.: 459868-92-9 (phosphate)

Indications: ovarian cancer

Related patent: WO2000042040

Mechanism of action: poly ADP-ribose polymerase (PARP) inhibitor

synthetic route:

New drug series: 2017 FDA approves new drugs and synthetic route analysis

Since 2017, the FDA has approved the approval of 12 new molecular entities and new biological products, including 9 related to hematology/oncology (cancer). In this public account, we will list some of the latest listed drugs and their symptoms. And po out the synthetic route of Ibrance drug molecules for everyone to learn.

Palbociclib (Ibrance)

 The FDA approved the launch of Pfizer palbociclib (IBRANCE) on March 31. Ibrance is an oral cyclin-dependent kinase (CDKs) 4 and 6 inhibitor. CDKs 4 and 6 are key regulators of the cell cycle that are capable of triggering cell cycle progression. Ibrance's indication in the United States is combined with letrozole for the treatment of estrogen receptor-positive, human epidermal growth factor receptor 2 negative (ER+/HER2-) postmenopausal advanced breast cancer patients, as an initial endocrine therapy-based approach Treating metastatic disease.

The effectiveness of Ibrance in this group of patients is based on the progression-free survival of the study. Continuous approval may be determined based on the clinical benefit of validating and describing the clinical study validation.

>>>>Molecular structure:

synthetic route:

Osimertinib (Tagrisso)

The FDA approved the listing of AstraZeneca Osimertinib (TAGRISSO) on March 30th. TAGRISSO is used in adult patients with locally advanced or metastatic EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) who have previously undergone treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) or after treatment. treatment.

Recently, the China Food and Drug Administration (CFDA) has approved the anti-cancer drug Tagrisso (omisertinib, AZD9291) 40mg and 80mg tablets as a daily oral medication.

Zejula (Niraparib)

The FDA approved the launch of Tesaro Zejula (niraparib) on March 27. Niraparib is an oral PARP inhibitor that targets cancers with BRCA1/2 mutations, developed for ovarian and breast cancer, and is FDA-approved for receiving complete or partial responses after platinum therapy However, maintenance treatment (delayed tumor growth) in patients with ovarian epithelial cancer, fallopian tube cancer, and primary peritoneal cancer with relapsed disease. According to estimates by the National Cancer Institute, there will be 22,000 new cancer patients and 14,000 deaths in the United States in 2017.

Zejula is the third FDA-approved PARP inhibitor after the FDA continues AstraZeneca Lynparza (Olapani, 2014/12/19) and Clovis Oncology Rubraca (rucaparib, 2016/12/19).

Bavencio (Avelumab)

The FDA approved the Bavencio (avelumab) 20mg/ml injection on March 23 for the treatment of metastatic Merkel cell carcinoma in adolescents and adults over 12 years of age. Bavencio has received FDA-approved breakthrough drug qualifications, and this is the fourth published PD-1/PD-L1 drug in the world, based on the response rate and response duration data, which is approved by the FDA for priority review. It was also the first PD-L1 monoclonal antibody approved for the treatment of metastatic Merkel cell carcinoma.


Metastatic Merkel cell carcinoma is a rare invasive skin tumor with a 1-year survival rate of less than 50% and a 5-year survival rate of less than 20%. The efficacy and safety of Avelumab in the treatment of Merkel cell carcinoma was demonstrated in a one-arm, open, multicenter study codenamed JAVELINMerkel200. The JAVELIN Merkel 200 study included 88 patients with metastatic Merkel cell carcinoma confirmed by histopathology and undergoing chemotherapy. 65% received one therapy and 35% received 2 or more therapies, given once every 2 weeks. Treatment with avelumab 10 mg/kg until disease progression or intolerance toxicity. The results showed a total response rate of 33%, of which 11% were complete remission and 22% were partial remission. Among the respondents, 86% survived for more than 6 months, 45% lasted for more than 12 months, and the response duration was 2.8 to 23.3 months.


The PD-1 antibody drug inhibits the binding of PD-L1 (expressed in cancer cells) to PD-1 (expressed in T cells), thereby activating T cells and the acquired immune system, and attacking cancer cells. Bavencio received an FDA priority review and breakthrough treatment approval, while Bavencio was identified as an orphan drug.

Keytruda (Pembrolizumab)

The US FDA has accelerated the approval of Keytruda (pembrolizumab) for the treatment of advanced (metastatic) non-small cell lung cancer (NSCLC) for disease progression after other drug treatments and for the expression of a patient with PD-L1 protein. Keytruda is approved for use with a companion diagnostic test, PD-L1 IHC 22C3 pharmDx, the first test to detect PD-L1 expression in non-small cell lung cancer. Keytruda is the first approved drug to block the cellular pathway known as PD-1, which limits the body's immune system from attacking melanoma cells. Keytruda is intended for the following treatments: with ipilimumab [ipilimumab], a type of immunotherapy. A gene mutation in tumor expression in melanoma patients is called BRAF V600, and Keytruda is intended for use after treatment with ipilimumab and a BRAF inhibitor, a treatment that blocks mutations in the BRAF gene.

Kisqali (Ribociclib)


The FDA approved the approval of Novartis Kisqali (ribociclib, LEE011) on March 13 for the first-line treatment of HR+/HER2-late or metastatic breast cancer with aromatase inhibitors. Kisqali received FDA approval for breakthrough drug and priority review channels, and the NDA review time lasted only 4.5 months. Kisqali is the second CDK4/6 inhibitor in the world after Pfizer Ibrance (palbociclib).

In a phase III MONALEESA-2 study involving 668 postmenopausal HR+/HER2-late or metastatic breast cancer patients, ribociclib combined with letrozole as a first-line therapy compared with letrozole monotherapy in the interim analysis The risk of disease progression or death is reduced by 44%. Ribociclib + letrozole median PFS significantly prolonged (19.3 months ~ not reached), and letrozole group 14.7 months (13.0 ~ 16.5 months). After 11 months of follow-up, the PFS of the two groups were 25.3 and 16.0 months, respectively. Total lifetime data has not yet been obtained.

CDK4/6 is a very early target. In 2001, Pfizer Ibrance came out. Because of its new mechanism, the mechanism of biological function is not clear. Second, the early so-called CDK4/6 inhibitors have poor selectivity and toxicity. It was not until 2009 that it entered the second phase clinical trial. However, after the approval of the listing of Ibrance, the market performance is very amazing. It broke through 2 billion US dollars in the second year of listing. Now it has become the most worthy of Pfizer's new drug listed in recent years.

Compared with letrozole monotherapy, Kisqali+letrozole significantly improved progression-free survival and reduced the risk of disease progression or death by 44%, which was statistically significant. Kisqali received FDA's breakthrough drug status and priority approval, and the FDA approved the drug for only four and a half months. HER2 negative, HR positive is the main type of postmenopausal breast cancer patients, accounting for about 60%, estimated to reach 10 billion US dollars in the market. According to economic analysts, Kisqali will likely become the next heavy drug.


Nivolumab (Opdivo)

Bristol-Myers Squibb announced on February 2 that the US Food and Drug Administration (FDA) officially approved Nivolumab for intravenous treatment of locally advanced or metastatic urothelial carcinoma (mUC), during or after platinum-containing chemotherapy Progression of the disease occurs; or disease progression occurs within 12 months of receiving platinum-containing chemotherapy as a neoadjuvant or adjuvant therapy. The indication is a rapid approval based on the rate of tumor remission and duration of response, and its subsequent approval will depend on the clinical benefit of the validation trial1. The recommended dose of Nivolumab for the treatment of metastatic urothelial carcinoma is 240 mg, intravenous infusion for more than 60 minutes, and the treatment period is once every two weeks. Continued administration until disease progression or intolerable toxicity. Clinical data from CheckMate-275 showed that 19.6% (95% CI: 15.1-24.9; 53/270) responded to Nivolumab, with 2.6% (7/270) of patients with complete remission and 17% of patients with partial remission (46/). 270). Among patients who responded, the median duration of remission was 10.3 months (time range 1.9+-12.0+ months) and the median onset time was 1.9 months (time range 1.6-7.2 months).

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