On March 25, 2021 Gilead Sciences, Inc. (Nasdaq: GILD) reported that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for sacituzumab govitecan-hziy (SG) for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received at least two prior therapies, including at least one prior therapy for locally advanced or metastatic disease (Press release, Gilead Sciences, MAR 25, 2021, View Source [SID1234577172]). The MAA is now under accelerated review by the EMA, in recognition of the product being considered of major interest for public health and therapeutic innovation.

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SG is a first-in-class therapy targeting Trop-2, a protein frequently expressed in multiple types of epithelial tumors, such as TNBC, where high expression is associated with poor survival and relapse. Currently, in the European Union (EU), there is no authorized standard treatment regimen with proven benefit in overall survival (OS) for patients with previously treated metastatic TNBC.

"Metastatic triple-negative breast cancer is an aggressive and life-threatening cancer. Unfortunately, for many people with this cancer, there are not enough effective treatment options and their prognosis is extremely poor," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "The validation of our EU marketing application is an important step toward addressing the significant unmet medical need for people with metastatic triple-negative breast cancer."

SG (under the tradename Trodelvy) received accelerated approval by the U.S. Food and Drug Administration (FDA) to treat adult patients with metastatic TNBC who have received at least two prior therapies for metastatic disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

In addition to the European Union, regulatory reviews of SG in metastatic TNBC are currently underway in the U.K., Canada, Switzerland and Australia, as well as in Singapore through our partner Everest Medicines. SG is also under review by the FDA for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a platinum containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic setting, and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.

About Triple-Negative Breast Cancer (TNBC)

TNBC is an aggressive type of breast cancer, accounting for approximately 15% of all breast cancers. The disease is diagnosed more frequently in younger and premenopausal women and is highly prevalent in African American and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited human epidermal growth factor receptor 2 (HER2). Medicines targeting these receptors therefore are not typically effective in treating TNBC.

About the ASCENT Study

The Phase 3 ASCENT study, an international, multi-center, randomized confirmatory trial, enrolled more than 500 patients with relapsed/refractory metastatic TNBC who had received at least two prior therapies for metastatic disease. Patients were randomized to receive either sacituzumab govitecan-hziy or a chemotherapy chosen by the patients’ treating physicians. The primary endpoint of the study was progression-free survival (PFS) in patients without brain metastasis at baseline. Secondary endpoints include PFS for the full study population, OS, objective response rate (ORR), duration of response (DoR), and time to response. More information about ASCENT is available at View Source

About Sacituzumab Govitecan-Hziy

SG is an antibody and topoisomerase inhibitor conjugate directed to the Trop-2 cell surface antigen, a protein frequently expressed in multiple types of epithelial tumors, including TNBC, where high expression is associated with poor survival and relapse.

In addition to multiple ongoing studies of SG in triple-negative breast cancer, it is being developed as an investigational treatment for metastatic urothelial cancer, hormone receptor-positive/HER 2-negative metastatic breast cancer, and metastatic non-small cell lung cancer, either as a monotherapy or in combination with other agents.

Important Safety Information for SG as included in the U.S. Prescribing information for Trodelvy.

Recommendations for the use of SG outside of the U.S. (including final safety information for prescribers) will be assessed as part of ongoing and future Marketing Authorization Applications.

WARNING: NEUTROPENIA AND DIARRHEA

SG can cause severe or life-threatening neutropenia. Withhold SG for absolute neutrophil count (ANC) below 1500/mm3 on Day 1 of any cycle or ANC below 1000/mm3 on Day 8 of any cycle. Withhold SG for neutropenic fever.

Monitor blood cell counts periodically during treatment. Consider Granulocyte Colony-Stimulating Factor (G-CSF) for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.

Dose modifications may be required due to neutropenia. Febrile neutropenia occurred in 6% (24/408) of patients treated with SG, including 8% (9/108) of patients with mTNBC after at least 2 prior therapies. Less than 1% (1/408) of patients had febrile neutropenia leading to permanent discontinuation. The incidence of Grade 1-4 neutropenia was 64% in patients with mTNBC (n=108). In all patients treated with SG (n=408), the incidence of Grade 1-4 neutropenia was 54%; Grade 4 neutropenia occurred in 13%. Less than 1% (2/408) of patients permanently discontinued treatment due to neutropenia.
Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold SG until resolved to ≤ Grade 1 and reduce subsequent doses.

Diarrhea occurred in 63% (68/108) of patients with mTNBC and 62% (254/408) of all patients treated with SG. In each population, events of Grade 3-4 occurred in 9% (10/108) of mTNBC patients and 9% (36/408) of all patients treated with SG. Four out of 408 patients (<1%) discontinued treatment because of diarrhea. Neutropenic colitis was observed in 2% (2/108) of patients in the mTNBC cohort and 1% of all patients treated with SG.
Contraindications: Severe hypersensitivity reaction to SG.

Hypersensitivity

SG can cause severe and life-threatening hypersensitivity, including anaphylactic reactions. Hypersensitivity reactions occurred within 24 hours of dosing in 37% (151/408) and Grade 3-4 hypersensitivity occurred in 1% (6/408) of all patients treated with SG (n=408). The incidence of hypersensitivity reactions leading to permanent discontinuation of SG was 1% (3/408).
Pre-infusion medication for patients receiving SG is recommended. Observe patients closely for infusion-related reactions during each SG infusion and for at least 30 minutes after completion of each infusion. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use.
Nausea and Vomiting

SG is emetogenic. Nausea occurred in 69% (74/108) of patients with mTNBC and 69% (281/408) of all patients treated with SG. Grade 3 nausea occurred in 6% (7/108) and 5% (22/408) of these populations, respectively. Vomiting occurred in 49% (53/108) of patients with mTNBC and 45% (183/408) of all patients treated with SG. Grade 3 vomiting occurred in 6% (7/108) and 4% (16/408) of these patients, respectively.
Premedicate with a 2- or 3-drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK-1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV).
Withhold SG doses for Grade 3 nausea or Grade 3-4 vomiting at the time of scheduled treatment administration and resume with additional supportive measures when resolved to Grade ≤ 1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.
Use in Patients with Reduced UGT1A1 Activity

Individuals who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia and may be at increased risk for other adverse events following initiation of SG treatment. Closely monitor patients with reduced UGT1A1 activity for severe neutropenia. The appropriate dose for patients who are homozygous for UGT1A1*28 is not known and should be considered based on individual patient tolerance to treatment.
In 84% (343/408) of patients who received SG (up to 10 mg/kg on Days 1 and 8 of a 21-day cycle) and had retrospective UGT1A1 genotype results available, the incidence of Grade 4 neutropenia was 26% (10/39) in patients homozygous for the UGT1A1*28 allele, 13% (20/155) in patients heterozygous for the UGT1A1*28 allele, and 11% (16/149) in patients homozygous for the wild-type allele.
Embryo-Fetal Toxicity

SG contains a genotoxic component and can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during treatment with SG and for 6 months following the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with SG and for 3 months after the last dose.
Lactation

Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 1 month after the last dose of SG.

Adverse Reactions

Most common adverse reactions (incidence >25%) in patients with mTNBC are nausea (69%), neutropenia (64%), diarrhea (63%), fatigue (57%), anemia (52%), vomiting (49%), alopecia (38%), constipation (34%), rash (31%), decreased appetite (30%), abdominal pain (26%), and respiratory infection (26%).

On March 25, 2021 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, reported that it signed a partnership agreement with Kyowa Kirin Pharmaceutical Research, Inc., a subsidiary of Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company, to discover novel antibodies for therapeutic use against an undisclosed G protein-coupled receptor (GPCR) target molecule (Press release, Twist Bioscience, MAR 25, 2021, View Source [SID1234577171]).

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"We are committed to using novel, differentiated technologies to develop best-in-class therapeutics while expediting the discovery process," said Andrew McKnight, President and Chief Scientific Officer, Kyowa Kirin Pharmaceutical Research, Inc. "We look forward to a productive and exciting partnership with Twist Bio that will allow us to discover optimized antibody therapeutics from their diverse libraries at a rapid pace."

Under the terms of the agreement, Twist Biopharma, a division of Twist Bioscience, will leverage its unique "Library of Libraries" for biologics discovery and its proprietary discovery capabilities to discover novel GPCR target specific antibodies for Kyowa Kirin. Twist identifies proprietary antibodies that are precisely designed to match sequences that occur in the human immune system due to its unique ability to manufacture DNA at scale. This precise and rational approach to antibody library creation, combined with advanced bioinformatics expertise and automation of the early discovery processes, expedites antibody discovery – decreasing risk, increasing speed, and lowering the failure rate for antibody therapeutic development. Using this approach, Twist has also created target-class focused libraries against difficult to drug target classes, such as GPCRs; these libraries will be put to use in the collaboration. Twist received an upfront payment upon signing and Kyowa Kirin retains an option to obtain development and commercial rights to any antibodies resulting from the agreement.

"Kyowa Kirin specializes in leveraging antibody engineering to develop innovative, life-changing medicines. That expertise complements Twist’s unique approach to efficient and robust antibody discovery and optimization," said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience.

On March 28, 2021 CytRx Corporation (OTCQB: CYTR) ("CytRx" or the "Company"), a specialized biopharmaceutical company focused on research and development for the oncology and neurodegenerative disease categories, reported on its results for the fourth quarter and fiscal year ended December 31, 2020 (Press release, CytRx, MAR 25, 2021, View Source [SID1234577170]). In addition, CytRx highlighted developments pertaining to its licensing agreements with ImmunityBio, Inc. (NASDAQ: IBRX) ("ImmunityBio") and Orphazyme A/S (NASDAQ: ORPH) ("Orphazyme") as well as Centurion Biopharma. The Company’s 10-K has been filed with the U.S. Securities and Exchange Commission.

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Steven A. Kriegsman, Chairman and Chief Executive Officer of CytRx, commented:

"The past year was a transformative one for CytRx. We executed a strategic pivot that has positioned us to cut corporate costs, maintain a stable capital position, and nimbly manage our portfolio of licensing agreements and strategic assets. Our Board of Directors also took concrete steps to strengthen the Company’s corporate governance, including commencing a search for a new independent director with strong biotechnology experience. We are very excited about the year ahead now that Orphazyme is preparing for prospective regulatory approvals for arimoclomol in the treatment of Niemann-Pick disease Type C and ImmunityBio is expanding its scope of clinical trials involving aldoxorubicin to treat advanced-stage pancreatic cancer. In our view, CytRx has achieved robust momentum and operating tailwinds as fiscal year 2021 begins."

Fiscal Year 2020 Financial Overview

CytRx concluded the fiscal year ended December 31, 2020 with cash on hand of approximately $10 million, which management believes is sufficient to fund ongoing operations for the foreseeable future.
The Company recorded a net loss of $6.7 million for the fiscal year ended December 31, 2020, compared to a net loss of $7.2 million for the fiscal year ended December 31, 2019.
General and administrative expenses were $6 million for the fiscal year 2020, compared with $7.4 million in 2019. This sizable decrease was primarily due to a reduction in stock-based compensation expenses.
Research and development expenses were $0.8 million for the fiscal year, compared with $0.4 million for 2019. This was due to increased consulting expenditures related to the establishment of a regulatory plan and new strategic initiatives for Centurion Biopharma’s assets.
Based on a current projection of expenditures for fiscal year 2021, the Company’s monthly cash burn rate is estimated to be approximately $406,000 per month. This twelve-month estimate is down from a previous projection of approximately $423,000 per month at the close of the third quarter of fiscal year 2020.
Fiscal Year 2020 Highlights

Orphazyme Highlights

As previously disclosed, CytRx’s agreement with Orphazyme can deliver up to $120 million in potential milestone payments and future single- and double-digit royalties paid on sales of arimoclomol.
CytRx is positioned to receive up to $10 million in potential milestone payments in 2021 based on possible U.S. and European approvals for arimoclomol to treat Niemann-Pick disease Type C ("NPC").
In September 2020, Orphazyme announced that the U.S. Food and Drug Administration ("FDA") accepted, with Priority Review, its New Drug Application ("NDA") for arimoclomol for the treatment of NPC.
In November 2020, Orphazyme announced that it submitted a Marketing Authorisation Application ("MAA") to the European Medicines Agency ("EMA") for approval of arimoclomol in the treatment of NPC.
In early December 2020, Orphazyme announced the expansion of its U.S. presence and workforce ahead of potential FDA approval of arimoclomol in the treatment of NPC.
In addition to establishing its U.S. headquarters in Chicago, Orphazyme recruited more than 30 U.S. employees. Orphazyme also named three U.S. leaders to its global executive team.
In late December 2020, Orphazyme disclosed that the FDA extended its review period with a standard extension of three months in order to complete its NDA review. The updated Prescription Drug User Fee Act ("PDUFA") target action date is June 17, 2021.
Recently, Orphazyme announced the appointment of Christophe Bourdon as its new Chief Executive Officer, effective as of April 1, 2021.
As reported by Orphazyme, Mr. Bourdon has successfully launched a variety of products in demanding environments, making him an ideal individual to lead Orphazyme as it prepares for a potential commercial launch of arimoclomol.
He joins from Amgen, Inc., where he has held the role of Senior Vice President, General Manager for the U.S. Oncology Business. He was leading commercialization planning and execution for several products.
Previously, Mr. Bourdon was Senior Vice President of Europe, Middle East, Africa and Canada at Alexion Pharmaceuticals Inc. as the company launched two breakthrough ultra-orphan drugs and negotiated payor access across the United Kingdom, Germany, France, Italy and Canada. He holds an MBA from IMD business school (Switzerland) and a BA from ISG (France).
Recently, Orphazyme also announced MIPLYFFA as the global brand name for arimoclomol and expanded its NPC Early Access Program in the U.S. and opened similar programs in France and Germany.
ImmunityBio Highlights

As previously disclosed, CytRx’s agreement with ImmunityBio can deliver up to $343 million in potential milestones and future single- and double-digit royalties paid on sales of aldoxorubicin’s use for multiple tumor types.
This past summer, the Chief Executive Officer of ImmunityBio spoke about the successful experimental treatment delivered to former Senate Majority Leader Harry Reid for his stage IV pancreatic cancer. Former Nevada Senator Reid has described himself as being in "complete remission" after receiving experimental combination immunotherapy that included aldoxorubicin.
In October 2020, ImmunityBio and NantKwest, Inc. ("NantKwest") announced the addition of a third cohort to their ongoing Phase 2 study of a novel combination immunotherapy, which includes aldoxorubicin, for locally advanced or metastatic pancreatic cancer (QUILT-88). The third cohort will enable pancreatic cancer patients who have failed all approved standards of care to participate in the study.
In December 2020, ImmunityBio and NantKwest announced their proposed merger and plans to create a leading immunotherapy and cell therapy company.
In their announcement, the companies noted the combination of ImmunityBio’s immunotherapy platforms – including aldoxorubicin – and NantKwest’s Natural Killer cell platform have already resulted in complete responses in aggressive and late-stage metastatic cancers.
In January 2021, ImmunityBio and NantKwest announced that their ongoing Phase 2 clinical trials of a novel combination immunotherapy – which includes aldoxorubicin – for locally advanced or metastatic pancreatic cancer had produced early indications of increased survival rates for patients with no other approved treatment options.
Interim results of the three-cohort trials, known as QUILT 88, showed median survival rates of more than double that of the historic rate in patients with advanced metastatic pancreatic cancer (for which no other FDA approved treatment exists).
Recently, ImmunityBio and NantKwest announced the closing of their merger, with ImmunityBio now trading on the NASDAQ under ticker symbol IBRX.
Additional Corporate Highlights

In August 2020, CytRx announced its plan to add a new independent member to its Board of Directors by no later than the one-year anniversary of the 2020 Annual Meeting of Shareholders. The Company has retained a leading recruitment firm to support the search process.
Throughout 2020, Mr. Kriegsman and Lead Director Louis Ignarro, PhD have pursued third-party financing and strategic partnership opportunities to advance pre-clinical and clinical studies for Centurion BioPharma’s high-potential assets.
Discussions with prospective partners and investors remain ongoing. There are no formal strategic financing updates to report at this time.
As of December 31, 2020, CytRx maintained federal and state net operating loss carryforwards – not subject to limitation under Section 382 of the Internal Revenue Code – of $258.3 million and $252.7 million, respectively, available to offset against future taxable income.
In February 2021, CytRx announced that it is now a part of the LD Micro Index (the "Index").
The Index is designed to give the most accurate representation of the intraday activity of microcap stocks in North America.
In March 2021, CytRx participated in the H.C. Wainwright Global Life Sciences Conference and the Virtual 33rd Annual ROTH Conference.
Mr. Kriegsman’s virtual presentation may be accessed on the News and Events page of the CytRx website.

On March 25, 2021 Genetron Holdings Limited ("Genetron Health" or the "Company", NASDAQ:GTH), a leading precision oncology platform company in China that specializes in offering molecular profiling tests, early cancer screening products and companion diagnostics development, reported unaudited preliminary financial results for the fourth quarter and full year ended December 31, 2020 (Press release, Genetron Health Technologies, MAR 25, 2021, View Source [SID1234577169]).

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2020 Financial Highlights

Recorded total revenue of RMB133.9 million (US$20.5 million) for the fourth quarter of 2020 and RMB424.5 million (US$65.1 million) for the full year 2020, representing 30.1% and 31.3% increases over the same period of 2019, respectively.
HCCscreenTM, our most advanced liquid-biopsy early screening product for hepatocellular carcinoma, is currently commercialized as LDT in China. LDT revenue derived from HCCscreenTM sales, as well as IVD revenue largely driven by the sales of S5 instrument and 8-gene Lung Cancer Assay (Tissue), grew significantly in 2020.
Gross margin improved to 62.8% for the fourth quarter 2020 and 61.3% for the full year 2020, compared to 44.5% and 44.8% in the same period of 2019, respectively.
Operating loss narrowed to RMB268.4 million (US$41.1 million) for 2020, from RMB306.9 million in 2019.
Non-IFRS loss(1) improved to RMB215.7 million (US$33.1 million) in 2020, compared to RMB280.2 million in 2019.
2020 Business and Recent Highlights

Successfully raised US$256 million gross proceeds from IPO on Nasdaq.
Early detection – HCCscreenTM:
Genetron Health announced new data on 1,615 patients from its HCCscreenTM prospective cohort study (the "HIT" study). The assay demonstrated 88% sensitivity and 93% specificity, compared to 71% and 95%, respectively, for ultrasound plus AFP combined. HCCscreenTM also achieved 40.9% PPV and 99.3% NPV (detailed press release here).
Exclusive strategic partnership with Chia Tai Tianqing Pharmaceutical Group, a subsidiary of Sino Biopharmaceutical Limited (HKEX: 1177), targeting the hospital market in China.
Selected by the National Cancer Center in China and the Wuxi municipal government for a public health initiative, composing of 150,000 tests over three years.
Received Breakthrough Device Designation by the U.S. FDA.
Joined national R&D project led by the Ministry of Science and Technology in China on lung and digestive cancer early screening.
Obtained NMPA approval on 8-gene Lung Cancer Assay (Tissue), which together with Genetron S5, form a highly efficient in-hospital NGS solution with a two-day turnaround time.
Entered into an exclusive global licensing agreement with ImmuQuad Biotechnologies to develop and commercialize minimal residual disease (MRD) assays in hematologic cancer.
Dr. Yun-fu Hu, formerly deputy director of the U.S. FDA’s Center for Devices and Radiological Health (CDRH) division, joined Genetron Health as Chief Medical Officer. Dr. Hu is tasked to lead the Company’s product development, IVD registration, regulatory affairs, and biopharma business.
Note:
(1) Non-IFRS loss for the period is defined as loss for the period excluding share-based compensation expenses, fair value change and other loss of financial instruments with preferred rights.

"In 2020, despite the challenges caused by the global pandemic, we completed a successful IPO and made significant commercial and clinical progress across all of our business lines. We delivered robust revenue growth with 31.3% year-over-year increase, and we are particularly pleased with the commercial uptakes of HCCscreenTM and our IVD products. Compared to a year ago, our gross margin expanded to 61.3% from 44.8%, and we also markedly improved our SG&A operational efficiencies," remarked Mr. Sizhen Wang, co-founder and CEO of Genetron Health. "We announced new HCCscreenTM data from our prospective cohort study, which showed overall better sensitivity data, and comparable specificity data versus the standard-of-care. We are encouraged by the further validation of this leading liquid-biopsy early detection assay, and will move forward to initiate an NMPA registrational study in the second quarter of this year."

"In 2021, based on the current environment and providing no further major COVID-19-related disruptions in our key markets, we are forecasting our sales to grow around 45% to 47% to reach RMB615 million to RMB625 million. On the pipeline front, we plan to provide case-control early screening data for colorectal cancer this year. Thanks to our Mutation CapsuleTM early screening technology, we are advancing well on our plans to expand our single-cancer assay to become a multi-cancer product. We also continue to make progress on our MRD projects in liver and colorectal cancers. Overall, Genetron Health is well-positioned to capture market share in the fast-growing precision oncology sector, and we are excited about our growth prospects. More importantly, we remain highly committed to developing innovative products that would benefit cancer patients and save more lives," concluded Mr. Wang.

Fourth Quarter 2020 Unaudited Preliminary Financial Results

Total revenue for the fourth quarter 2020 increased by 30.1% to RMB133.9 million (US$20.5 million) from RMB102.9 million in the same period of 2019.

Diagnosis and monitoring revenue increased by 44.0% to RMB123.5 million (US$18.9 million) in the fourth quarter 2020 from RMB85.8 million in the same period of 2019. The increase was driven by the growth in the revenues generated from both the provision of LDT services, particularly in early screening, and the sale of IVD products.

Revenue generated from the provision of LDT services increased by 48.5% to RMB96.9 million (US$14.9 million) during the fourth quarter 2020 from RMB65.3 million in the same period of 2019. In the fourth quarter, sales of LDT services included sales of our early screening test, HCCscreenTM, which contributed to growing portion of total LDT revenue. LDT diagnostic tests sold in the fourth quarter 2020 totaled approximately 5,340 units, representing a decrease of 16% compared to the number of LDT diagnostic tests sold in the same period of 2019, primarily due to the resurgence of COVID-19 in our key sales territories in the fourth quarter. However, the average selling price increased compared to the same period in 2019, attributable to a shift to higher value products such as Onco PanScan, and better pricing management.
Revenue generated from sale of IVD products increased by 29.5% to RMB26.5 million (US$4.1 million) in the fourth quarter 2020 from RMB20.5 million in the fourth quarter 2019. The increase was mainly driven by the increase in the number of assays and sequencing platforms sold in the fourth quarter 2020.

On March 25, 2021 Pfizer Inc. (NYSE:PFE) reported the peer-reviewed publication of real-world evidence (RWE) demonstrating that first-line therapy with IBRANCE (palbociclib) in combination with letrozole was associated with improved real-world progression-free survival (rwPFS) and overall survival (OS) in women with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) metastatic breast cancer (mBC) compared with letrozole alone (Press release, Pfizer, MAR 25, 2021, View Source;Metastatic-Breast-Cancer [SID1234577168]). These findings represent the first comprehensive comparative effectiveness analysis of survival outcomes for a CDK 4/6 inhibitor in routine clinical practice and were published online in Breast Cancer Research.

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At a median follow-up of approximately two years and after balancing for baseline demographic and clinical characteristics, median rwPFS was 20.0 months with IBRANCE plus letrozole versus 11.9 months with letrozole alone (HR 0.58: 95% CI, 0.49 to 0.69; p<0.0001) in this observational, retrospective real-world analysis. Median OS was not reached among patients in the IBRANCE group and was 43.1 months among patients in the letrozole group (HR 0.66: 95% CI, 0.53 to 0.82; P=0.0002). These findings represent a 42% reduction in the risk of progression and a 34% reduction in the risk of death.

"Real-world evidence is woven into the fabric of how we innovate and advance care for patients with breast cancer, supporting our randomized clinical trials," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "With more than six years of patient experience, a positive benefit-risk profile, strong clinical data and robust real-world data, the totality of evidence solidifies the role of IBRANCE plus endocrine therapy as a treatment for patients with HR+, HER2- metastatic breast cancer."

The analysis also showed the two-year OS rate was 78.3% in the IBRANCE group and 68.0% with letrozole. The rwPFS and OS benefits were generally consistent across all subgroups, including younger patients (18-50 years of age) and site or extent of metastases.

"Real-world evidence is increasingly used to complement traditional randomized clinical trial data to better understand a therapy’s effectiveness in routine clinical practice and inform treatment decisions," said Angela DeMichele, M.D., lead researcher and Professor in Breast Cancer Excellence in the Perelman School of Medicine at the University of Pennsylvania. "The findings from this landmark real-world study align with the positive impact that I have seen in my own patients treated with IBRANCE combination therapy."

The data for this retrospective observational analysis was collected from the Flatiron Health de-identified longitudinal database, which includes patient records from Flatiron’s network of more than 280 community cancer clinics and partnerships with major academic cancer centers across the U.S. This real-world cohort includes more than 1,400 women with HR+, HER2- mBC with any extent of visceral disease. Safety data were not collected as part of this analysis.

The data from this real-world analysis is consistent with available data from the Phase 3 PALOMA-2 trial, which studied IBRANCE plus letrozole versus placebo plus letrozole as initial endocrine-based therapy in post-menopausal women with estrogen-receptor positive (ER+), HER2- mBC. However, this observational analysis differs from the randomized clinical trial in several ways. The studies have different endpoints and there are inherent limitations in real-world observational studies, including lack of randomization, lack of uniform timing or type of clinical assessments and challenges with missing data. OS data is being collected in the PALOMA-2 randomized clinical trial but is not yet mature.

About the IBRANCE Real-World Evidence Program

Since the initial approval by the U.S. Food and Drug Administration more than six years ago, IBRANCE has been prescribed to more than 380,000 patients across more than 100 countries. With this breadth of real-world experience, Pfizer is working to build the most extensive body of RWE for a CDK 4/6 inhibitor. This RWE program is generating data from multiple studies involving more than 4,000 patients around the world and continues to expand. These studies – IRIS, POLARIS, MARIA, and MADELINE – include diverse patient populations treated in everyday clinical practice and are collecting data related to clinical outcomes, translational data and quality of life endpoints, which complement the data generated from the PALOMA randomized clinical trials. Pfizer will continue to share new data from these studies with the scientific community as results becomes available.

About IBRANCE (palbociclib) 125 mg tablets and capsules

IBRANCE is an oral inhibitor of CDKs 4 and 6,1 which are key regulators of the cell cycle that trigger cellular progression.2,3 In the U.S., IBRANCE is indicated for the treatment of adult patients with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy.

The full U.S. Prescribing Information for the IBRANCE tablets and the IBRANCE capsules can be found here and here.

IMPORTANT IBRANCE (palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with CDK4/6 inhibitors, including IBRANCE when taken in combination with endocrine therapy. Across clinical trials (PALOMA-1, PALOMA-2, PALOMA-3), 1.0% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no fatal cases were reported. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported.

Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g. hypoxia, cough, dyspnea). In patients who have new or worsening respiratory symptoms and are suspected to have developed pneumonitis, interrupt IBRANCE immediately and evaluate the patient. Permanently discontinue IBRANCE in patients with severe ILD or pneumonitis.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients to consider sperm preservation before taking IBRANCE. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis.

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