[exclusive] 2018 pharmaceutical giant new drug R & D event (Pfizer)

Based on Pfizer's press release, this paper reviews Pfizer's major new drug R & D events in 2018 (1) FDA / EMA approval trends 1 Glasdegib approved by (s) NDA or MAA (1) FDA on November 2, 2018, Pfizer announced that FDA approved glasdegib, the company's oral hedgehog pathway inhibitor, for the treatment of newly diagnosed acute myeloid leukemia (AML) patients aged ≥ 75 years and not suitable for intensive induction chemotherapy Glasdegib is the first hedgehog inhibitor approved by FDA for AML, which must be combined with cytarabine Glasdegib clinical trial subjects did not include patients with severe renal function injury and patients with moderate to severe liver function injury (2) FDA approved lorlatinib On November 2, 2018, Pfizer announced that the FDA has accelerated the approval of the company's third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor, lorlatinib, for the treatment of ALK positive metastatic NSCLC patients who had previously been treated with clozatinib and at least one other ALK inhibitor but were progressing or were treated with aleutinib or seretinib but were progressing (3) The FDA approved talazoparib on October 16, 2018 Pfizer announced that the FDA had approved talazoparib, a polyadenyldiphosphate ribose polymerase-1 (PARP-1) inhibitor of the company, for the treatment of HER2 negative local late stage or metastatic breast cancer patients with harmful or suspected harmful BRCA mutations The announcement did not make further comments (4) On September 27, 2018, the FDA approved dacomitinib, a kinase inhibitor of Pfizer, for the first-line treatment of metastatic NSCLC patients with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21l858r substitution mutation Researchers at the Chinese University of Hong Kong say late NSCLC with EGFR mutations is particularly common in Asian populations In early 2018, the FDA decided to prioritize the use of dacomitinib for the treatment of advanced or metastatic NSCLC with EGFR activated mutations (5) FDA / EMA approved the new indications of tofetab ① ulcerative colitis on August 1, 2018, Pfizer company issued a notice that EMA approved the company's JAK kinase inhibitor tofetab citrate (10mgbid ×≥ 8 weeks → 5mg or 10mgbid) for the treatment of moderate to severe ulcerative colitis with poor efficacy, rebound or poor tolerance after conventional treatment of biological products Tofetab citrate is the only oral drug and JAK inhibitor approved for the treatment of ulcerative colitis This indication of tropib citrate was previously approved by FDA on May 30, 2018 ② Active psoriatic arthritis on June 28, 2018, Pfizer company released a message that EMA approved tofetib citrate 5mgbid combined with methotrexate for the treatment of active psoriatic arthritis patients who had previously been treated with DMARDs but had poor or intolerant remission effect Tofetab citrate is the only JAK kinase inhibitor approved for this indication Topiramate citrate is the world's first JAK kinase inhibitor approved by FDA in December 2012 At present, the indications approved by FDA include rheumatoid arthritis, ulcerative colitis and active psoriatic arthritis (6) On July 31, 2018, Pfizer released a notice that EMA had approved trazimera, the company's trazimera, for the treatment of breast cancer with overexpression of HER2 and metastatic gastric or gastric esophageal junction adenocarcinoma with overexpression of her Trastuzumab is a HER2 / neu receptor antagonist developed by Genentech company and approved by FDA in September 1998 Its current indications include: treatment of breast cancer with HER2 overexpression; treatment of metastatic gastric cancer with her overexpression and adenoma at the gastric esophageal junction Currently, FDA has approved trastuzumab biological analogues from celltrion and mylan (7) On July 20, 2018, Pfizer released a notice that the FDA approved the company's non gliding biological analogues (trade name: neupogen) for all indications of the reference drugs, mainly including: Used to reduce the risk of infection characterized by neutropenic fever in patients with nonmyelogenous malignancies treated with bone marrow inhibitor anticancer drugs associated with severe neutropenia with hyperthermia It is used to shorten the time required for neutrophil recovery and the duration of fever in patients with acute myeloid leukemia after induction or consolidation chemotherapy It is used to shorten the duration of neutropenia or related clinical sequelae (such as neutropenic fever) in patients with non myeloid malignant tumors who received myeloablative chemotherapy and bone marrow transplantation successively The autologous hematopoietic progenitor cells were mobilized into the peripheral blood for the collection of leukocyte elimination (8) On July 13, 2018, the FDA approved the new indication of enzalutamide Pfizer and Japan's ansteras company jointly issued a notice that the FDA approved enzalutamide to be used for the treatment of non metastatic castrated resistant prostate cancer (CRPC) patients, making it the only oral drug approved to treat both metastatic and non metastatic CRPC at the same time Enzalutamide is an androgen receptor antagonist that was originally developed by medivation and astilus under an agreement reached in 2009 Medivation was acquired by Pfizer in 2016 Enzalutamide was approved by FDA as early as 2012 As of December 20, 2018, 33 patients in the world have used enzalutamide for treatment (9) On April 23, 2018, the EMA approved gemtuzumabogamicin Pfizer announced that the EMA approved the gemtuzumabogamicin combined with daunorubicin and cytarabine for the treatment of newly diagnosed CD33 positive patients with acute myeloid leukemia (AML) (age ≥ 15 years, except for acute promyelocytic leukemia) Gemtuzumabozogamicin is the first drug approved by EMA to target CD33 and to treat AML The expression rate of CD33 in AML patients is more than 90% Pfizer said AML is a rapidly growing and life-threatening blood and bone marrow cancer If not treated, AML patients will die months or even weeks after diagnosis AML is the most common type of acute leukemia, accounting for about 80% of the cases of acute leukemia In Europe, there are 1688 new cases of AML every year Previously, gemtuzumabozogamicin was approved by FDA in 2017 2 No (s) NDA or MAA rejected 2 FDA / EMA drug declaration and review trends 1 Drug declaration and review with positive progress (1) bevacizumab biological analogues get positive opinions from CHMP under EMA On December 14, 2018, Pfizer announced that its declared bevacizumab (formerly known as Avastin) bioequivalent drug (to be named zirabev) obtained positive opinions from the human drugs Committee (CHMP) under the European Union EMA, thus paving the way for its listing in the European Union Bevacizumab is a kind of monoclonal antibody drug of vascular endothelial growth factor resistance agent, which was launched by genetec, a subsidiary of Roche company, in 2004 The current FDA approved indications include metastatic colon or rectal cancer, metastatic breast cancer, late stage non-small cell lung cancer, advanced and / or metastatic renal cell cancer and persistence , recurrent or metastatic brain cancer Prior to that, Amgen's bevacizumab bio similar drug (trade name mvasi) has been approved by FDA (September 2017) and EMA (January 2018) 2 Frustrated drug application and review (1) application for expanded indications of sunitinib was rejected by CHMP on February 23, 2018 Pfizer released a notice saying that CHMP under EMA had passed a resolution recently, saying that it was not recommended that EMA approve sunitinib of the company as an adjuvant therapy to treat patients with renal cell carcinoma who are prone to relapse after nephrectomy Sunitinib is a kinase inhibitor approved by FDA in January 2006 At present, the indications approved by FDA are: ① for the treatment of gastrointestinal stromal tumors which were treated by imatinib before but were in progress or intolerable; ② for advanced renal cell carcinoma (III) clinical trial dynamics 1 Clinical trials with positive progress (1) clinical trials with new indications of enzalutamide with positive results On December 20, 2018, Pfizer and astaris Co., Ltd jointly announced that the three-stage arches test aimed at evaluating the efficacy and safety of enzalutamide combined with androgen deprivation therapy (ADT) in the treatment of metastatic sex hormone sensitive prostate cancer (mhspc) reached the main end point The results showed that enzalutamide combined with ADT improved the radiologic progression free survival period of mhspc patients The effect of ADT is better than that of ADT alone The results of the basic safety analysis of the arches trial are also similar to the previous safety characteristics of enzalutamide in castrated resistant prostate cancer (CRPC) patients (2) Progress in clinical trials of rituximab (pf-05280586) On December 2, 2018, Pfizer announced at the annual meeting of the American Association of Hematology that a 52 week clinical trial comparing the safety and efficacy of its rituxan / mabtera biological analogue (pf-05280586) and its original research drug (rituxan / mabtera) in the treatment of patients with painless follicular lymphoma (reflectionsb328-06) reached the main clinical end of its 26 week total remission rate (ORR) The results showed that the orr of pf-05280586 and mabthera groups were 75.5% and 70.7% respectively after 52 weeks of continuous treatment, and the estimated 1-year progression free survival rate of the two groups was 76.4% and 81.2%, respectively There was no significant difference between the above parameters In addition, their security characteristics are similar to each other Previously, FDA has accepted the declaration of pf-05280586 and will make a final decision in the second quarter of 2019 Rituximab is a kind of monoclonal antibody drug that can specifically combine with CD20 antigen on B-cell membrane and initiate B-cell-mediated cell-mediated immune response Currently, the indications approved by FDA include: non Hodgkin's lymphoma, chronic lymphocytic leukemia, granulomatosis and pemphigus vulgaris Currently, celltrion's rituximab biological analogue (trade name truxima) has been approved by FDA (3) On November 8, 2018, Pfizer and Merck Co., Ltd jointly issued a notice that a three-stage javelin renal101 trial aimed to compare the efficacy and safety of avelumab combined with acitinib vs sunitinib in the first-line treatment of advanced renal cell carcinoma patients achieved positive results It is the first time that immunotherapy combined with tyrosine kinase inhibitor can be used in the treatment of any tumor type, and the treatment effect of PD-L1 + population and the whole population has been significant Pfizer's alliance with Merck plans to launch the administrative declaration based on the interim analysis results of the progression free survival period Avelumab is an anti programmed death ligand-1 (PD-L1) antibody, which was first approved by FDA in March 2017 The current indications of the trade name bavencio include: ① patients with Merkel cell tumor (MCC) aged ≥ 12 years (accelerated approval); ② patients with locally advanced or metastatic bladder epithelioma (accelerated approval) Acitinib was approved by the FDA in January 2012