On October 23, 2019 Edwards Lifesciences Corporation (NYSE: EW), the global leader in patient-focused innovations for structural heart disease and critical care monitoring, reported financial results for the quarter ended September 30, 2019 (Press release, Edwards Lifesciences, OCT 23, 2019, View Source [SID1234542458]).

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Third Quarter and Recent Highlights

Sales grew 21% to $1.1 billion; underlying1 sales grew 19%
TAVR sales grew 26%; underlying sales grew 27%
R&D spending up 21% versus prior year to 18% of sales
EPS was $1.30; adjusted1 EPS was $1.41
2019 adjusted EPS guidance raised to $5.50 to $5.65 from $5.20 to $5.40
$27 million charge related to TAVR strategy
FDA approved SAPIEN 3 and SAPIEN 3 Ultra systems indication expansion
"We are very pleased to report strong third quarter results, which reflected a large increase in the number of patients that were treated with transcatheter heart valve therapy," said Michael A. Mussallem, chairman and CEO. "Our results were significantly higher than expected this quarter following the strong PARTNER 3 trial evidence that led to the recent FDA indication expansion of our SAPIEN 3 and SAPIEN 3 Ultra systems. Additionally, at a recent clinical meeting it was exciting to observe new evidence that once again demonstrated significant quality of life improvements for patients that received SAPIEN valves."

Third Quarter 2019 Results

Sales for the quarter ended September 30, 2019 were $1.1 billion, up 21 percent over the prior year, or 19 percent on an underlying basis. Diluted earnings per share for the quarter were $1.30, while adjusted earnings per share grew 32 percent, higher than expected, to $1.41.

Transcatheter Aortic Valve Replacement (TAVR)

For the quarter, the company reported TAVR sales of $700 million, an increase of 26 percent over the third quarter last year, or 27 percent on an underlying basis. Global average selling prices remained stable, and the company estimates its global competitive position was consistent with the second quarter and prior year.

"The recent indication expansion approval of our SAPIEN 3 and SAPIEN 3 Ultra systems represents a significant milestone and allows all patients diagnosed with severe aortic stenosis to be considered for TAVR based on their individual needs," said Mussallem.

He added, "While still early in the 2020 forecasting process and difficult to predict, we are modeling a return to low double-digit global TAVR procedure growth next year, consistent with our estimate of a $7 billion opportunity in 2024."

Transcatheter Mitral and Tricuspid Therapies (TMTT)

The company made important progress in the third quarter in advancing its portfolio of technologies to bring important solutions to underserved mitral and tricuspid patients with few options today. Enrollment is ongoing in the CLASP IID and CLASP IIF Pivotal Trials. In September the company received FDA approval for the CLASP IITR Pivotal Trial to study the PASCAL system in patients with symptomatic severe tricuspid regurgitation. The company remains on track to initiate a U.S. pivotal trial of the SAPIEN M3 system before the end of the year. Third quarter sales in TMTT were $10 million, lifted principally by commercial sales of the PASCAL transcatheter mitral system in Europe. For full year 2019, Edwards now expects TMTT revenue to be below $40 million as the company continues a disciplined introduction and premium pricing strategy, which is moderating site activation.

Surgical Structural Heart and Critical Care

Surgical Structural Heart sales for the quarter were $204 million, up 11 percent compared to the third quarter last year, or up three percent on an underlying basis. Growth was lifted by the sales of premium products, particularly through adoption of the INSPIRIS RESILIA aortic valve, which drove an increasing share of surgical aortic valve procedures.

Critical Care sales were $180 million for the quarter, representing an increase of ten percent versus the third quarter last year, or up seven percent on an underlying basis. All product categories and geographies contributed to this performance, including our HemoSphere advanced monitoring platform.

Additional Financial Results

For the quarter, the company’s adjusted gross profit margin was 75.9 percent, compared to 75.5 percent in the same period last year. This improvement was driven primarily by the favorable impacts from foreign exchange and product mix, partially offset by spending in support of the new European device regulations and manufacturing variances.

Selling, general and administrative expenses increased 14 percent to $306 million for the quarter, driven by transcatheter structural heart field personnel related expenses, including expanding the TMTT field organization in Europe.

Research and development for the third quarter increased 21 percent to $196 million, or 18 percent of sales. This increase was primarily the result of significant investments in the company’s transcatheter structural heart programs, including generating clinical evidence.

During the quarter, the company recorded an additional $27 million charge, primarily inventory, related to last quarter’s strategic decisions regarding its transcatheter aortic valve portfolio.

Adjusted free cash flow for the third quarter was $319 million, defined as cash flow from operating activities of $437 million, less capital spending of $76 million, and excluding a $42 million tax benefit related to the company’s previously announced litigation settlement.

Cash, cash equivalents and short-term investments totaled $1.4 billion at September 30, 2019. Total debt was $594 million.

Outlook

For 2019, the company now expects total sales around the top of its previous $4.0 billion to $4.3 billion range. Additionally, the company raised its full year 2019 adjusted earnings per share guidance to $5.50 to $5.65 from $5.20 to $5.40.

"We are very pleased with our strong year-to-date performance. As patients and clinicians increasingly choose TAVR, we remain optimistic about the long-term growth opportunity. We are committed to aggressively investing in our future, consistent with our focused innovation strategy. We remain confident that the innovative therapies resulting from our investments will benefit a broader group of patients suffering from structural heart disease and continue to drive strong organic growth," said Mussallem.

On October 23, 2019 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported that the Company will have two presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting on November 6-10, 2019 at the Gaylord National Convention Center in National Harbor, MD (Press release, Mirati, OCT 23, 2019, View Source [SID1234542457]).

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Oral Presentation Details:

Title: Sitravatinib in combination with nivolumab demonstrates clinical activity in platinum-experienced patients with urothelial carcinoma (UC) who progressed on prior immune checkpoint inhibitor (CPI)
Presentation Date and Time: Saturday, November 9th at 6:15pm EST – 6:30pm EST
Presenter: Pavlos Msaouel, M.D., Ph.D., The University of Texas MD Anderson Cancer Center
Abstract ID: 12620
Concurrent Session 310: Combination Phase 1-2 Clinical Trials
Location: Gaylord National Convention Center

Poster Presentation Details:

Title: Sitravatinib and nivolumab for resectable oral cavity squamous cell carcinoma window of opportunity study (SNOW)
Poster Session Date and Time Saturday, November 9th at 7:00am EST – 8:30pm EST
Presenter: Marc Oliva, M.D., Princess Margaret Hospital, University of Toronto
Poster Number: P400
Poster Presentation Hours: 12:35pm – 2:05pm and 7:00pm – 8:30pm EST on Saturday, November 9th
Location: Gaylord National Convention Center

About Sitravatinib

Sitravatinib is an investigational spectrum-selective kinase inhibitor that potently inhibits receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, Mer), split family receptors (VEGFR2, KIT) and RET. As an immuno-oncology agent, sitravatinib is being evaluated in combination with nivolumab (OPDIVO), an anti-PD-1 checkpoint inhibitor, in patients whose cancers have progressed despite treatment with a checkpoint inhibitor. Sitravatinib’s potent inhibition of TAM and split family RTKs may overcome resistance to checkpoint inhibitor therapy through targeted reversal of an immunosuppressive tumor microenvironment, enhancing antigen-specific T cell response and expanding dendritic cell-dependent antigen presentation. Sitravatinib is being evaluated in multiple clinical trials to treat patients who are refractory to prior immune checkpoint inhibitor therapy, including the ongoing potentially registration-enabling Phase 3 trial of sitravatinib in combination with a checkpoint inhibitor in non-small cell lung cancer (NSCLC). In addition, sitravatinib combinations with checkpoint inhibitors are being evaluated in selected checkpoint inhibitor naïve patients.

Sitravatinib is also being evaluated as a single-agent in a Phase 1b expansion clinical trial emphasizing enrollment of patients whose tumors harbor specific mutations in the CBL protein. When CBL is inactivated by mutation, multiple RTKs, including TAM, VEGFR2 and KIT, are dysregulated and may act as oncogenic tumor drivers in NSCLC and melanoma.

On October 23, 2019 GlaxoSmithKline (LSE/NYSE: GSK) reported that the company has received approval from the U.S. Food and Drug Administration (FDA) for an expanded indication for Zejula (niraparib), an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor for the treatment of advanced ovarian, fallopian tube, or primary peritoneal cancer patients, who have been treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either (Press release, GlaxoSmithKline, OCT 23, 2019, View Source [SID1234542453]):

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A deleterious or suspected deleterious BRCA mutation, or
genomic instability and who have progressed more than six months after response to the last platinum-based chemotherapy.
Patient selection is based on an FDA-approved companion diagnostic for Zejula.
This represents the first time a PARP inhibitor has been approved for use in patients beyond those with a BRCA-positive (BRCA+) mutation as monotherapy in the late-line treatment setting. Now women with late-line, HRD-positive (HRD+) disease are eligible to be treated with a PARP inhibitor.

Axel Hoos, MD, PhD, SVP Oncology R&D, GSK, said: "This new indication reinforces our commitment to providing treatment options for more women impacted by ovarian cancer, especially those with high unmet needs. We look forward to continuing our clinical development program of Zejula and understanding its full potential as a treatment for people living with ovarian cancer."

This new indication is based on the QUADRA study, a Phase 2, multi-center, open-label, single-arm clinical study representing a real world, difficult-to-treat patient population with high unmet needs. QUADRA is the largest clinical trial of a PARP inhibitor in women who received three or more treatments for advanced ovarian cancer. The trial enrolled a broad patient population including women with BRCA+ platinum-sensitive, resistant and refractory disease as well as women with HRD+ platinum-sensitive disease.

Clinically meaningful and durable benefit was demonstrated in the FDA-indicated patient population with an objective response rate (ORR) of 24% (95% CI, 16–34). A median duration of response (mDOR) of 8.3 months (95% CI, 6.5–not estimable) was observed.

Additional analyses were conducted in various sub populations where efficacy of Zejula was also demonstrated for patients with tBRCA and GIS; defined as deleterious or suspected deleterious somatic or germline BRCA mutation and genomic instability score (GIS ≥42) as identified with Myriad’s myChoice companion diagnostic test, respectively:

tBRCA+ platinum-sensitive disease, ORR of 39% (95% CI, 17,64);
tBRCA+ platinum-resistant disease, ORR of 29% (95% CI, 11,52);
tBRCA+ platinum-refractory disease, ORR of 19% (95% CI, 4,46); or
non-BRCA mut, GIS-positive, platinum-sensitive disease, ORR of 20% (95% CI, 8,37).
The safety profile was consistent with that seen in the Phase 3 NOVA trial in the recurrent maintenance population. Most common grade ≥3 adverse reactions reported in ≥10% of patients in the QUADRA study included thrombocytopenia (28%), anemia (27%), neutropenia (13%) and nausea (10%).

Dr. Kathleen Moore, Lead Investigator of the QUADRA study; Director, Oklahoma TSET Phase 1 Program; Associate Professor, Section of Gynecologic Oncology, Stephenson Cancer Center, University of Oklahoma, said: "Ovarian cancer has a high rate of recurrence, so there is a real need for therapies for women whose cancer has progressed through multiple lines of treatment and who have few or no options left. It’s meaningful to see that Zejula has been approved as a late-line treatment for women including those with and without BRCA mutations."

Ovarian cancer affects nearly 222,000 women in the U.S., and approximately 85% of women with advanced ovarian cancer will see the disease return. With each recurrence, the time a woman may spend without her cancer progressing until the next recurrence gets shorter. Currently, there are few effective options available for treatment of platinum-resistant/refractory advanced ovarian cancer or HRD+ ovarian cancer in the late-line setting. Zejula received initial FDA approval in March 2017 for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. It is the only oral, once-daily PARP inhibitor.

About QUADRA
QUADRA is a large multi-center, open-label, single-arm, Phase 2 registrational study that evaluated the safety and activity of niraparib in adult patients with relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who were treated with three or more previous chemotherapy regimens. Four hundred and sixty-three patients were enrolled and received oral niraparib at a starting dose of 300 mg once daily. Treatment was continued until disease progression. The primary objective was the proportion of patients achieving an investigator-assessed confirmed overall response in patients with HRD+ tumors, including patients with BRCA and without BRCA mutations, sensitive to their last platinum-based therapy. Additional objectives of the study were to evaluate the efficacy of niraparib in the broad late-line ovarian cancer population overall, and in subgroups defined by clinical and molecular biomarkers, such as platinum-sensitivity and BRCA+ and HRD status.

The Myriad myChoice companion diagnostic test was utilized during this clinical trial and has been approved by the FDA as the companion diagnostic test to determine HRD+ status as either tBRCA and/or a genomic instability score (GIS ≥42). GIS is an algorithmic measurement of Loss of Heterozygosity (LOH), Telomeric Allelic Imbalance (TAI), and Large-scale State Transitions (LST).

Information about Myriad myChoice companion diagnostic is available at Myriad.com.

About Ovarian Cancer
Approximately 22,000 women are diagnosed each year with ovarian cancer in the U.S. Ovarian cancer is the fifth most frequent cause of cancer death among women. Despite high response rates to platinum-based chemotherapy in the front-line, approximately 85% of patients will experience disease recurrence. Once the disease recurs, its considered incurable with time to each future recurrence getting shorter. Late-line treatment options for women with ovarian cancer are few, with the proportion of patients achieving an overall response typically less than 10% when treated with chemotherapy.

About Niraparib
Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in multiple pivotal trials. GSK is building a robust niraparib clinical development program by assessing activity across multiple tumor types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development program for niraparib includes a Phase 3 trial as monotherapy maintenance treatment in patients with first-line ovarian cancer (PRIMA), data from this study were recently presented at the European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper), a Phase 3 study as a first-line triplet maintenance treatment in ovarian cancer (FIRST), and a Phase 2 study of niraparib combined with bevacizumab maintenance treatment in advanced ovarian cancer (OVARIO).

Several combination studies are also underway, including trials of niraparib plus pembrolizumab in metastatic, triple-negative breast cancer and advanced, platinum-resistant ovarian cancer (TOPACIO). Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in Japan.

Important Safety Information

Zejula may cause serious side effects, including:

Bone marrow problems called Myelodysplastic Syndrome (MDS) or a type of blood cancer called Acute Myeloid Leukemia (AML). Some people who have ovarian cancer and who have received previous treatment with chemotherapy or certain other medicines for their cancer have developed MDS or AML during treatment with Zejula. MDS or AML may lead to death.

Symptoms of low blood cell counts (low red blood cells, low white blood cells, and low platelets) are common during treatment with Zejula. They can be a sign of serious bone marrow problems, including MDS or AML. These symptoms may include the following:

Weakness
Feeling tired
Weight loss
Frequent infections
Fever
Shortness of breath
Blood in urine or stool
Bruising or bleeding more easily
Uncommonly, fever associated with low white blood cells is observed during treatment with Zejula.

Your doctor will do blood tests to check your blood cell counts before treatment with Zejula. You will be tested weekly for the first month of treatment with Zejula, monthly for the next 11 months of treatment, and from time to time afterward.

High blood pressure is common during treatment with Zejula, and it can become serious. Your doctor will check your blood pressure and heart rate at least weekly for the first two months, then monthly for the first year, and as needed thereafter during your treatment with Zejula.

Before starting to take Zejula, tell your doctor about all of your medical conditions, including if you:

Have heart problems
Have high blood pressure
Are pregnant or plan to become pregnant. Zejula may harm an unborn baby and may cause loss of pregnancy (miscarriage)
If you are able to become pregnant, you should use effective birth control (contraception) during treatment with Zejula and for 6 months after taking the last dose of Zejula
If you are able to become pregnant, your doctor may perform a pregnancy test before you start treatment with Zejula
You should tell your doctor right away if you become pregnant
Are breastfeeding or plan to breastfeed
Zejula may harm your baby. You should not breastfeed your baby during treatment with Zejula and for 1 month after taking the last dose of Zejula
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Zejula include the following:

Heart not beating regularly
Nausea
Constipation
Vomiting
Pain in the stomach area
Mouth sores
Diarrhea
Indigestion or heartburn
Dry mouth
Tiredness
Loss of appetite
Urinary tract infection
Shortness of breath
Cough
Rash
Changes in liver function or other blood tests
Pain in your joints, muscles, and back
Headache
Dizziness
Change in the way food tastes
Trouble sleeping
Anxiety
Sore throat
Changes in the amount or color of your urine
If you have certain side effects, then your doctor may change your dose of Zejula, temporarily stop, or permanently stop treatment with Zejula.

These are not all the possible side effects of Zejula. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

For full prescribing information visit www.zejula.com/prescribing-information.

myChoice companion diagnostic is a registered trademark of Myriad.

About GSK Oncology
GSK is focused on maximizing patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilizing modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On October 23, 2019 The Board of Directors of McKesson Corporation (NYSE:MCK) reported a regular dividend of 41 cents per share of common stock (Press release, McKesson, OCT 23, 2019, View Source [SID1234542452]). The dividend will be payable on January 2, 2020, to stockholders of record on December 2, 2019.

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On October 23, 2019 Cleveland Diagnostics, Inc., a clinical-stage company focused on developing next-generation diagnostic tests for the detection of cancers, reported that its chief medical officer, Mark Stovsky, MD, participated in an Impact Session at the 2019 Medical Innovation Summit organized by Cleveland Clinic (Press release, Cleveland Diagnostics, OCT 23, 2019, View Source [SID1234542451]).

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The Medical Innovation Summit, which is celebrating its 17th year, is covering a wide range of topics including artificial intelligence, new drug discovery, advanced diagnostics development, and the personalization of healthcare. Clinicians, strategists, venture capital groups and other ground-breakers joined renowned clinical experts to discuss, disrupt and deal head-on with issues confronting today’s healthcare ecosystem.

During the Impact Session entitled "Early Detection: A Snag in the System," Dr. Stovsky, CMO of Cleveland Diagnostics and urologist at the Cleveland Clinic, joined other leading industry and government experts to discuss current challenges and opportunities in early detection in cancer. Other topics included early diagnosis of untreatable diseases and the subsequent lack of protocol to move forward.

"We are indeed honored to have Dr. Stovsky join a distinguished panel of speakers on cancer early detection at this meeting," said Arnon Chait, PhD, CEO of Cleveland Diagnostics. "The discussion was both timely and enlightening, and it is clear that some of the leading players in the space are finally beginning to refocus resources on early cancer detection as perhaps the only viable long-term and cost-effective solution to curable approaches in cancer."

Cleveland Diagnostics was recently awarded Breakthrough Device Designation by FDA, which allows Cleveland Diagnostics to work more closely and frequently with FDA to expedite the review of its prostate cancer assay, IsoPSA. Two recent multicenter clinical trials, in which the diagnostic accuracy of IsoPSA was compared to that of traditional prostate-specific antigen (PSA), suggested that IsoPSA has superior diagnostic accuracy in detecting high-grade prostate cancer. Cleveland Diagnostics has a pipeline of simple, cancer-specific and highly cost effective cancer blood tests using the same proprietary core technology.

"The traditional approach to early detection strategies for prostate cancer based on standard serum PSA testing is limited by relatively poor diagnostic accuracy and predictive value. We believe the IsoPSA assay will fill a major gap in this space by providing clinicians with a tool that has improved diagnostic accuracy – particularly for the detection of high grade, clinically actionable prostate cancer," said Dr. Stovsky. "I am thrilled to have had the opportunity to join industry and government leaders, such as Grail, Intel, and NCI, to discuss innovative ways to develop more effective approaches to cancer early detection that will improve the lives of patients worldwide. While we believe that the IsoPSA assay will improve early detection strategies for prostate cancer, we also look forward to exploring ways to work together to design a clinically superior, cost effective early detection paradigm, which might combine virtual screening, protein biomarker testing — such as IsoPSA — and DNA liquid biopsy as a comprehensive approach to this challenging clinical problem."