Boston Scientific Announces Results For First Quarter 2020

On April 29, 2020 Boston Scientific Corporation (NYSE: BSX) reported that sales of $2.543 billion during the first quarter of 2020 (Press release, Boston Scientific, APR 29, 2020, View Source [SID1234556794]). This represents growth of 2.0 percent on a reported basis, 3.2 percent on an operational1 basis and a decline of 2.9 percent on an organic2 basis, all compared to the prior year period. The company reported GAAP earnings of $11 million or $0.01 per share (EPS), compared to GAAP earnings of $424 million or $0.30 per share a year ago, and achieved adjusted earnings per share of $0.28 for the period, compared to $0.35 a year ago.

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"During this global pandemic, we are grounded in the urgency of providing important medical products and therapies to those who need them–in particular, many patients with acute needs," said Mike Mahoney, chairman and chief executive officer, Boston Scientific. "We continue to balance short-term adjustments to our plans while strengthening our long-term strategy to serve our customers and deliver high performance. I’m confident in our ability to bring meaningful, innovative products to market, and grateful for our team’s winning spirit as we navigate the impact of these challenges."

First quarter financial results and recent developments:

Reported GAAP earnings of $0.01 per share. Achieved adjusted earnings per share of $0.28. On March 30, 2020, the company withdrew its Q1 2020 sales and EPS guidance, originally provided on February 5, 2020.
Generated first quarter sales growth/(decline) in our reportable segments4, compared to the prior year period:
MedSurg: 1.1 percent reported, 2.1 percent operational and organic
Rhythm and Neuro: (7.2) percent reported, (6.2) percent operational and (8.6) percent organic
Cardiovascular: 5.5 percent reported, 7.0 percent operational and (2.5) percent organic
Generated first quarter regional5 sales growth/(decline), compared to the prior year period:
U.S.: 3.5 percent reported and operational
EMEA (Europe, Middle East and Africa): (1.6) percent reported and 1.3 percent operational
APAC (Asia-Pacific): (6.4) percent reported and (4.8) percent operational
Emerging Markets3: (10.1) percent reported and (5.4) percent operational
Received CE Mark for the ACURATE neo2 Aortic Valve System, a next-generation transcatheter aortic valve implantation (TAVI) technology to treat patients with severe aortic stenosis that builds on the clinical performance of the original ACURATE neo platform.
Received FDA approval for the DIRECTSENSE RF Technology, the only tool available to monitor the effect of radiofrequency (RF) energy delivery via changes in local impedance around the tip of a catheter during cardiac ablation procedures.
Received CE Mark for the SpyGlass Discover Digital Catheter, a novel single-use surgical endoscope, for use in diagnostic and therapeutic applications during pancreaticobiliary surgery and percutaneous procedures. SpyGlass Discover enables physician access to the pancreaticobiliary system, allowing them to take a single-stage approach to treating patients with bile duct stones.
Received an expanded indication from the FDA for the VENOUS WALLSTENT Self-Expanding Stent, which can now be used to treat patients suffering from blockages in the iliofemoral veins. Iliofemoral deep vein thrombosis (DVT) represents approximately one-quarter of all lower extremity DVT cases.6
Announced positive three-year data for the WATCHMAN Left Atrial Appendage Closure Device — the largest real-world analysis of the device to-date with 38,000 patients from the National Cardiovascular Data Registry (NCDR)-LAAO Registry — at the virtual meeting of the American College of Cardiology/World Congress of Cardiology and continue to demonstrate the device is safe and effective for a broad population of patients with non-valvular atrial fibrillation.
Published positive five-year clinical data in The Journal of Urology confirming that Rezûm Water Vapor Therapy is an effective, long-term treatment for men with benign prostatic hyperplasia (BPH) and offers sustained improvement of lower urinary tract symptoms and quality of life for patients while preserving sexual function. Only 4.4 percent of patients required surgical retreatment through the five years of the clinical trial, demonstrating the therapy’s durability.
Increased available liquidity to approximately $2.6 billion by entering into a new $1.25 billion term loan agreement to refinance borrowings under the company’s revolving credit agreement, and enhanced financial flexibility by amending financial covenants in outstanding credit arrangements.
Signed a virtual energy power purchase agreement (VPPA) that represents another key step the company has taken to achieve its goal of global carbon neutral manufacturing and distribution by 2030. The agreement will address the electricity load for the company’s U.S. operations, which represents 45 percent of its total carbon footprint.
Launched efforts to help address the global impact of COVID-19, including collaborations with the University of Minnesota and others to develop the Coventor, an emergency resuscitator granted Emergency Use Authorization by the FDA, and a reusable personal respirator, as well as the production of face shields for frontline healthcare workers.
Reached a definitive agreement to divest the company’s commercial Intrauterine Health franchise — comprised of the Symphion Tissue Removal System, the Resectr Tissue Resection Device and the Genesys HTA System — to Minerva Surgical. The transaction is expected to close in the coming days, subject to customary closing conditions.

Guidance for Remainder of 2020

On March 30, 2020, the company withdrew its sales and EPS guidance for the full year 2020, originally provided on February 5, 2020. Due to the uncertain scope and duration of the COVID-19 pandemic, timing of global recovery and economic normalization, the company is unable to estimate the overall impacts on its operations and financial results for the remainder of 2020.

Conference Call Information

Boston Scientific management will be discussing these results with analysts on a conference call today at 8:00 a.m. EDT. The company will webcast the call to interested parties through its website: www.bostonscientific.com. Please see the website for details on how to access the webcast. The webcast will be available for approximately one year on the Boston Scientific website.

Fennec Announces Proposed Public Offering of Common Shares

On April 29, 2020 Fennec Pharmaceuticals Inc. (NASDAQ:FENC) (TSX:FRX), a specialty pharmaceutical company focused on the development of PEDMARKTM (a unique formulation of sodium thiosulfate) for the prevention of platinum-induced ototoxicity from cisplatin in pediatric cancer patients, reported that it intends to offer its common shares in an underwritten public offering (Press release, Fennec Pharmaceuticals, APR 29, 2020, View Source [SID1234556935]). In addition, Fennec intends to grant the underwriters a 30-day option to purchase up to an additional 15% of its common shares offered in the public offering.

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Cantor Fitzgerald & Co. is acting as the sole book-running manager for the proposed offering. Wedbush PacGrow is acting as the co-manager.

The common shares are being offered by the Company pursuant to a registration statement previously filed with and declared effective by the Securities and Exchange Commission (the "SEC"). The offering will be made only by means of a prospectus. A preliminary prospectus supplement and an accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website located at View Source Copies of the preliminary prospectus supplement and the accompanying prospectus, when filed with the SEC, may also be obtained from Cantor Fitzgerald & Co., 499 Park Avenue, 6th Floor, New York, NY 10022, Attn: Capital Markets Department, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities, in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. The securities will not be offered or sold, directly or indirectly, in Canada or to any resident of Canada.

Vivoryon Therapeutics Announces Outcome of Exclusive Option Deal with MorphoSys

On April 29, 2020 Vivoryon Therapeutics AG (Euronext Amsterdam: VVY, ISIN DE0007921835) reported that MorphoSys has not exercised the exclusive option to license Vivoryon’s small molecule QPCTL inhibitors in the immuno-oncology field (Press release, Vivoryon Therapeutics, APR 29, 2020, View Source [SID1234556716]).

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During the option period, MorphoSys conducted preclinical studies to assess the potential of small molecule QPCTL inhibitors in oncology as well as the possible benefits of combining these inhibitors with MorphoSys’ proprietary program, tafasitamab, a compound in late-stage development for the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). In parallel, Vivoryon, based on its 2019 research collaboration with the University Medical Center Schleswig-Holstein, Campus Kiel, conducted a similar series of preclinical studies.

Ultimately, the data demonstrated a significant additive effect when QPCTL inhibitors were combined with CD20 and other antibodies, indicating that Vivoryon’s lead drug candidate, PQ912, could represent a novel approach for cancer therapy. Vivoryon’s orally available compounds target the QPCTL enzyme, which has been shown to be a modulator of the CD47-SIRP alpha interaction. Left unchecked, this interaction allows cancer cells to escape the body’s innate immune defense through inhibition of the phagocytic activity of macrophages.

Ulrich Dauer, CEO of Vivoryon Therapeutics commented: "Although we are disappointed by MorphoSys’ decision, we remain optimistic about collaborating with other leading oncology companies to further leverage the strength and versatility of our small molecule therapeutics in oncology."

United Therapeutics Corporation Reports
First Quarter 2020 Financial Results

On April 29, 2020 United Therapeutics Corporation (Nasdaq: UTHR) reported its financial results for the quarter ended March 31, 2020 (Press release, United Therapeutics, APR 29, 2020, View Source [SID1234556734]). First quarter net revenue decreased 2% to $356.3 million year-over-year while first quarter net revenue excluding Adcirca increased 0.4%, compared to the first quarter of 2019. First quarter diluted earnings per share (EPS) was $3.12 compared to an $11.32 per share loss in the first quarter of 2019. Non-GAAP diluted EPS of $3.61 was up 1% from the first quarter of 2019.

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"I’m proud of the efforts of the entire United Therapeutics team to ensure continued access to our life-sustaining therapies during this unprecedented time," said Martine Rothblatt, Ph.D., Chairman and Chief Executive Officer of United Therapeutics. "We’re excited that our supplemental new drug application to expand the potential Tyvaso patient population with the INCREASE study results remains on track for a mid-year filing and, along with our partner DEKA, we’re preparing for a July 2020 launch of our Remunity Pump."

Michael Benkowitz, President and Chief Operating Officer of United Therapeutics, commented, "We’re pleased with Remodulin’s continued resilience in the face of generic competition and Orenitram’s 18% year-over-year revenue growth, which we attribute to physician reception of the FREEDOM-EV data showing that Orenitram, when used in combination with an approved oral background therapy, delays disease progression and leads to improvement across key clinical parameters. We see these data, plus the recently announced publications demonstrating Orenitram’s positive effect on hemodynamics, risk status, and PAH-related healthcare costs, as enhancing Orenitram’s value proposition."

FIRST QUARTER 2020 FINANCIAL RESULTS

Revenues for the three months ended March 31, 2020 decreased by $6.3 million, as compared to the same period in 2019.

As of March 31, 2020, new patient starts from our treprostinil-based products (Remodulin, Tyvaso, and Orenitram) were not impacted as a result of the COVID-19 pandemic, but most of the prescriptions submitted by physicians for new patients as of this date pre-dated the outbreak in the United States. However, we have observed a decline in new prescriptions from our treprostinil-based products during the month of April 2020 that we believe is primarily due to the inability of patients to visit their physicians’ offices to determine whether our medicines may be appropriate, which could lead to a reduction in new patient starts and negatively impact our revenues. Refer to COVID-19 Impact and Our Efforts to Combat the Pandemic below for additional discussion.

Remodulin net product sales decreased by $10.2 million for the three months ended March 31, 2020, as compared to the same period in 2019. U.S. Remodulin net product sales decreased by $6.0 million and international Remodulin net product sales decreased by $4.2 million. The total decrease of $10.2 million primarily resulted from: (1) a decrease in quantities sold of $5.7 million; and (2) the $5.4 million impact of price reductions. U.S. patient demand for Remodulin during the three months ended March 31, 2020, remained consistent with the strong demand in 2019, following the initial transition of Remodulin patients to generic treprostinil in the first half of 2019.

Tyvaso net product sales for the three months ended March 31, 2020 decreased by $0.9 million, as compared to the same period in 2019, resulting from: (1) higher gross-to-net revenue deductions of $3.5 million; and (2) a decrease in quantities sold of $2.9 million; partially offset by a $5.5 million increase in revenue due to a January 2020 price increase.

Orenitram net product sales for the three months ended March 31, 2020 increased by $10.6 million, as compared to the same period in 2019, primarily resulting from: (1) an increase in quantities sold of $7.5 million; and (2) $3.7 million due to a January 2020 price increase.

Unituxin net product sales for the three months ended March 31, 2020 increased by $1.7 million, as compared to the same period in 2019, primarily resulting from $3.8 million due to April 2019 and January 2020 price increases, partially offset by a $2.0 million decrease due to a reduction in the number of vials sold.

Adcirca net product sales for the three months ended March 31, 2020 decreased by $7.5 million, as compared to the same period in 2019. This decrease was primarily due to a continuing decrease in bottles sold as a result of generic competition for Adcirca.

(1)Refer to Share-based compensation below.

Cost of product sales, excluding share-based compensation. The decrease in cost of product sales of $5.8 million for the three months ended March 31, 2020, as compared to the same period in 2019, was primarily attributable to a $3.3 million decrease in royalty expense for Adcirca as fewer bottles were sold as a result of generic competition for Adcirca.

(1)Refer to Share-based compensation below.

Research and development expense, excluding share-based compensation. Research and development expense decreased by $825.2 million for the three months ended March 31, 2020, as compared to the same period in 2019. Research and development expense for the treatment of cardiopulmonary diseases decreased by $830.4 million for the three months ended March 31, 2020, as compared to the same period in 2019, due to an $800.0 million upfront payment to Arena Pharmaceuticals, Inc. under our license agreement related to ralinepag and a $12.5 million payment under our license and collaboration agreement with MannKind Corporation, both of which occurred during the three months ended March 31, 2019.

Other Income, Net. The increase in "other income, net" of $2.9 million for the three months ended March 31, 2020, as compared to the same period in 2019, was primarily due to an increase in net unrealized and realized gains on equity securities of $13.4 million, partially offset by: (1) a $4.2 million increase of net unrealized and realized foreign currency losses; and (2) a $1.5 million impairment charge on a note receivable during the first quarter of 2020. During the three months ended March 31, 2020, we recognized a $22.5 million unrealized gain on an investment in a privately-held company and $6.1 million of net unrealized and realized losses on equity securities with readily determinable fair values. During the three months ended March 31, 2019, we recognized $3.0 million of unrealized gains on equity securities with readily determinable fair values.

Impairments of Investments in Privately-Held Companies. During the quarter ended March 31, 2020, we observed indicators of impairment of the value of two of the privately-held companies in which we hold an investment. We determined each of these investments in privately-held companies was impaired and recognized total impairment charges of $5.6 million. We did not recognize any impairment charges related to our investments in privately-held companies during the three months ended March 31, 2019.

Income Tax Expense. Income tax expense was $33.9 million for the three months ended March 31, 2020, as compared to income tax benefit of $156.0 million for the same period in 2019. The effective income tax rate (ETR) for the three months ended March 31, 2020 and 2019 was 20 percent and 24 percent, respectively. For the three months ended March 31, 2020, anticipated tax credits, state audit adjustments, and the foreign sales deduction, partially offset by non-deductible compensation and state tax expense, decreased our ETR. For the three months ended March 31, 2019, anticipated tax credits and the foreign sales deduction, partially offset by non-deductible compensation and state tax expense, increased our ETR due to the pre-tax loss that resulted primarily from the upfront $800.0 million payment under our license agreement with Arena Pharmaceuticals, Inc.

Non-GAAP Earnings

Non-GAAP earnings is defined as net income (loss), adjusted for: (i) share-based compensation expense (including expenses relating to stock options, restricted stock units, share tracking awards and our employee stock purchase plan); (ii) impairments of investments in privately-held companies; (iii) unrealized gain on investment in privately-held company; (iv) net unrealized and realized losses on equity securities; (v) other impairment charges; (vi) license-related fees; and (vii) tax impact on non-GAAP earnings adjustments.

(1)Recorded within operating expenses on our consolidated statements of operations.

(2)Recorded within impairments of investments in privately-held companies on our consolidated statements of operations.

(3)Recorded within "other income, net" on our consolidated statements of operations.

(4)Recorded within research and development on our consolidated statements of operations.

(5)For the three months ended March 31, 2020, the impairments of investments in privately-held companies and unrealized losses on equity securities had no impact on income tax expense to the extent that we record a valuation allowance for such items against deferred tax assets. The remaining items had an offsetting effect such that they had no net tax impact for the three months ended March 31, 2020.

COVID-19 IMPACT AND OUR EFFORTS TO COMBAT THE PANDEMIC

We are closely monitoring developments related to the COVID-19 pandemic and are making every effort to ensure we remain focused on the health and well-being of our patients and our employees while maintaining business continuity. At this time, it is too early to predict what impact this pandemic, and the associated economic downturn, will have on our business. While we remain confident in our prospects over the longer term, there is considerable uncertainty and lack of visibility regarding our near-term revenue growth prospects and product development plans due to the rapidly evolving situation. Therefore, we are no longer able to predict whether our full-year 2020 net revenues will grow compared to 2019.

We’re engaged in the fight against COVID-19. As a pulmonary health company, we are committed to deploying our research teams and development partners to investigate potential therapies for COVID-19 and related pulmonary conditions. Earlier this month, we expanded our existing collaboration with Celularity, Inc. to study the use of Celularity’s placental-derived natural killer cell therapy, CYNK-001, to treat patients with the novel coronavirus associated with COVID-19. The U.S. Food and Drug Administration (FDA) recently cleared Celularity’s investigational new drug application to evaluate CYNK-001’s safety, tolerability, and efficacy for the treatment of COVID-19 in a phase I/II study of up to 86 patients. Under our agreement with Celularity, our Lung Biotechnology subsidiary will support Celularity’s study of CYNK-001 as an antiviral treatment for COVID-19. We have global rights to commercialize CYNK-001 to treat COVID-19 and acute respiratory distress syndrome (ARDS), which is a major cause of patient morbidity and mortality associated with COVID-19. We are also exploring the use of other Celularity cell-based biologic products to treat ARDS. Finally, we are working with academic institutions to investigate the potential use of Tyvaso and Unexisome to treat ARDS and are expediting our biomechanical lung program to develop a version suitable for use in the hospital for COVID-19 patients needing oxygen support.

Our financial position is strong. We believe our healthy balance sheet makes us well-positioned to endure the impact of this pandemic. With enough cash, cash equivalents, and marketable securities on hand to fund our operations as we conduct them today for at least two years regardless of our future revenues, we are able to retain and hire new employees, continue our research and development and commercial activities, subject to the limitations described below, and make new strategic investments. Consequently, we expect to be able to return to "normal" operations rapidly once we are able to do so.

We have an ample supply of our products. In order to ensure access to our treprostinil-based products, and in accordance with our long-standing inventory policy, we have sufficient inventory of finished treprostinil-based products (Remodulin, Tyvaso, and Orenitram) to supply the market for two years at current levels of demand. In addition, we manufacture our own treprostinil active pharmaceutical ingredient (API) at our Silver Spring, Maryland facility and have three years’ worth of API on hand at any given time. These products and API supplies are all stored at our own warehouses in the United States. Manufacturing of our treprostinil-based products, both internally and at our contract manufacturers, continues mostly as usual, and we do not currently anticipate any supply shortages of our treprostinil-based products.

We also have approximately 14 months’ inventory of our Unituxin drug supply, plus raw materials for additional production, and intend to continue manufacturing Unituxin in quantities sufficient to meet current patient demand. Unlike our treprostinil-based products, Unituxin is a biologic with a shorter shelf life, so our ability to maintain longer-term inventories is limited; however, we do not currently anticipate any supply shortages of Unituxin.

We have redundant qualified manufacturing sites for our two current best-selling products: Remodulin and Tyvaso. Should either site be impacted by an outbreak, production activities could be diverted to the other qualified site, each of which is capable of supplying the worldwide market. Our internal manufacturing and packaging operations are independently staffed and physically segregated by technical capability (e.g., oral solid dose, aseptic vial filling, etc.) Should any internal operation be impacted by an outbreak, we believe that area and staff could shut down and isolate, respectively, without affecting the other manufacturing areas.

To date, we have not experienced any interruption of our supply of drug products and devices needed to support our ongoing clinical trials.

Distribution of drug product to patients continues without interruption. Our specialty pharmacy distributors, which we require to maintain at least 30 days’ worth of inventory on hand at any given time, continue to ship our products to patients and hospitals. Specialty pharmacies have assured us that they have exercised their continuity plans to avoid supply disruptions. They have also assured us that their nursing support services, which are required for therapy initiation and over the course of treatment to train patients to safely administer their medicine, continue through a combination of in-person and virtual visits. Similarly, we are not aware of any disruption to the distribution of Unituxin treatment for patients with neuroblastoma. As a contingency plan, we secured alternative product transportation capability that we believe will allow us to continue delivering products to distributors if traditional freight operations are disrupted.

Our commercial efforts continue but could be disrupted as a result of the COVID-19 pandemic. Our commercial field-based teams are meeting with prescribing physicians virtually instead of in person. As of March 31, 2020, COVID-19 has not had a material impact on our treprostinil-based therapies, positively or negatively, with respect to specialty pharmacy orders, new patient prescriptions or new patient starts. Thus far in April 2020, however, we have observed several COVID-19 related impacts on U.S. demand for our treprostinil-based therapies:

•One of our specialty pharmacy distributors placed a larger than normal order during April to increase its inventory beyond typical levels (but still within contractual requirements) to: (1) account for potential increased investigational use of Tyvaso for ARDS, which is a major cause of patient morbidity and mortality associated with COVID-19; (2) prepare for an anticipated increase in patient requests for 60- or 90-day refills (as compared to their typical 30-day supply); and (3) increase inventory levels across various locations to ensure uninterrupted business continuity during the COVID-19 pandemic.

•We have seen a reduction in new patient prescriptions across all of our treprostinil-based products throughout the month, which we believe is due to the inability of patients to visit their physician’s office to determine whether our medicines may be appropriate.

•While new patient starts remained steady during the first half of the month, we have experienced a decline in new patient starts in the second half of the month for the reasons noted above.

We cannot predict the impact of these events on our near-term revenues. We are uncertain as to how long the reduction in new patient prescriptions and new patient starts will last, whether there will be an increase in new prescriptions and new patient starts in later months due to pent up demand, or whether these events will materially impact orders from specialty pharmacy distributors since they place orders based on current utilization trends and contractual minimum and maximum requirements.

We remain on track to launch the Remunity Pump for Remodulin in July 2020, but recognize that the launch could be delayed or limited due to pandemic-related constraints experienced by physicians and patients, the specialty pharmacy distributors that we are engaging to prefill Remunity cartridges, or any delay in DEKA’s ability to supply devices to us.

Our clinical studies remain open, but many have paused new patient enrollment. Most of our ongoing clinical studies have paused enrollment during the pandemic, but patients already enrolled in studies continue to receive the study drug and complete necessary clinical evaluations as appropriate. To date, we have paused enrollment in the following studies, among others:

•PERFECT study related to Tyvaso in pulmonary hypertension associated with chronic obstructive pulmonary disease
•ADVANCE OUTCOMES and ADVANCE CAPACITY studies of ralinepag
•BREEZE and pivotal pharmacokinetics studies of Treprostinil Technosphere
•SAPPHIRE study of Aurora-GT
•phase I study of Unexisome for bronchopulmonary dysplasia
•phase I study of OreniPro

As such, we expect that completion and data readouts for several of our ongoing and planned studies will be delayed, but we do not currently expect delays of our potential product launch plans relative to the near-, medium-, and long-term windows described in our Form 10-Q under Research and Development. Despite the enrollment pause in many of our other clinical studies, we continue to enroll patients in our clinical study of our ex-vivo lung perfusion technology. In addition, while enrollment is paused we are exploring ways to continue and expand our efforts to enter into contracts with additional clinical study sites and complete other site activation activities for certain studies where practicable, in order to rapidly resume enrollment of our clinical studies at the appropriate time.

Our planned regulatory activities and interactions with the FDA continue. In March 2020, the FDA announced that it was canceling or postponing all non-essential meetings. At this time, we have not experienced any delays to our upcoming regulatory activities, such as:

•our planned new drug application (NDA) supplement for Tyvaso to incorporate the results of the INCREASE study
•our planned biologics license application (BLA) supplement for Unituxin to reflect recent clinical study results for relapsed/refractory neuroblastoma
•Medtronic’s efforts to satisfy FDA conditions to its premarket approval application (PMA) approval for the Implantable System for Remodulin

NEW PRODUCT COMMERCIALIZATION UPDATE

In our near-term time horizon, we expect to launch three products for pulmonary arterial hypertension (PAH): the Remunity Pump, the Trevyent system, and the Implantable System for Remodulin.

Remunity Pump for Remodulin. On February 24, 2020, we announced FDA clearance of the pharmacy-filled version of the Remunity Pump for Remodulin, developed in partnership with DEKA. We plan to make the Remunity Pump available to patients by July 2020. The Remunity Pump consists of a small, lightweight, ambulatory pump that is intended to have a service life of at least three years. The Remunity Pump uses disposable prefilled cassettes, which are connected to the pump. The pump was initially cleared by the FDA in May 2019 with instructions for patient filling. Our recent 510(k) clearance enables cassettes to be prefilled with Remodulin by contracted specialty pharmacy distributors in order to improve convenience for patients. We are also developing a version of the system that includes cassettes that are prefilled as part of the manufacturing process. Our partner DEKA and its affiliates continue manufacturing work on the Remunity Pump and our contracting work with compounding pharmacy partners continues.

Trevyent. We submitted a 505(b)(1) NDA to the FDA for our Trevyent disposable treprostinil pump system in June 2019. In April 2020, the FDA issued a complete response letter (CRL) related to our NDA indicating that some of the deficiencies previously raised by the FDA had not yet been addressed to its satisfaction. We are evaluating the letter and will provide updates on our plans to resubmit our NDA at a later date. We have one year from the date of the CRL to resubmit our NDA to the FDA, which is expected to trigger a six-month review period by the agency.

Implantable System for Remodulin (ISR). Developed in collaboration with Medtronic, the PMA for ISR was approved by the FDA in December 2017. However, our ability to launch the product is subject to our partner satisfying various conditions to its PMA approval. Medtronic continues to work toward satisfying these conditions, but in December 2019, due to recent FDA communications, Medtronic informed us that these conditions will not be satisfied in 2020. As such we expect a delay in the ISR launch until 2021.

RESEARCH AND DEVELOPMENT UPDATE

Updates on selected later-stage programs are below. As noted above, enrollment in the clinical trials mentioned below has been paused due to the COVID-19 pandemic.

Tyvaso in pulmonary hypertension due to interstitial lung disease (PH-ILD) — INCREASE. On February 24, 2020, we reported that the INCREASE study of Tyvaso in patients with PH-ILD met its primary endpoint of demonstrating improvement in six-minute walk distance (6MWD). Tyvaso also showed benefits across several key subgroups, including etiology of PH-ILD, disease severity, age, gender, baseline hemodynamics, and dose. Significant improvements were also observed in each of the study’s secondary endpoints, including reduction in the cardiac biomarker NT-proBNP, time to first clinical worsening event, change in peak 6MWD at Week 12, and change in trough 6MWD at week 15. Treatment with Tyvaso of up to 12 breaths per session, four times daily, in the INCREASE study was well tolerated and the safety profile was consistent with previous Tyvaso studies and known prostacyclin-related adverse events.

We expect to make the full results of the study available through upcoming journal publications and presentations at medical conferences. In addition, we plan to submit the results to the FDA by mid-year 2020 in support of an efficacy supplement (sNDA) to the Tyvaso new drug application, which we expect to result in revised labeling reflecting the outcome of the INCREASE study. In April 2020, in response to questions we submitted to the FDA along with a pre-sNDA meeting request and briefing package, the FDA indicated that the results of the INCREASE study appear to support our proposed indication of treatment of patients with PH-ILD to improve exercise ability and delay clinical worsening.

Treprostinil Technosphere dry powder inhaler – BREEZE. The BREEZE study (NCT03950739) seeks to evaluate 45 patients on a stable dose of Tyvaso after switching to our new dry powder inhaler (DPI) form of treprostinil, which we licensed from MannKind. The primary endpoint of the study is the number of subjects with treatment-emergent adverse events after three weeks of treatment with the DPI. In March 2020 we also commenced a second clinical study in healthy volunteers to compare the pharmacokinetics of Treprostinil Technosphere to Tyvaso.

We anticipate results of both of these studies in 2020, assuming that we can resume enrollment in a timely manner. We expect results of these two studies, combined with long-term stability studies of the DPI product, will form the basis of a 505(b)(1) new drug application to the FDA for our treprostinil DPI delivery product.

Unituxin in relapsed/refractory neuroblastoma — ANBL1221. We are pursuing an indication expansion for Unituxin for the treatment of pediatric patients with relapsed or refractory neuroblastoma based on the results of the Children Oncology Group’s ANBL1221 study (NCT01767194). We met with the FDA in April of this year to discuss the content needed to support a supplemental BLA. We’re working with Children’s Oncology Group (COG) to secure additional information ahead of a potential supplemental BLA filing.

Tyvaso in pulmonary hypertension due to chronic obstructive pulmonary disease (PH-COPD) — PERFECT. The PERFECT study (NCT03496623) seeks to evaluate Tyvaso in patients with PH-COPD. In a 30-week crossover study, 136 subjects will be randomized between inhaled treprostinil and placebo for a 26-week treatment period. The primary endpoint of the study is the change in 6MWD from baseline to week 12. A contingent design for the study allows for the evaluation of 314 patients in two parallel groups.

Ralinepag phase III development program — ADVANCE CAPACITY and ADVANCE OUTCOMES. We have two ongoing phase III clinical studies to support the potential registration of oral ralinepag for PAH.

ADVANCE CAPACITY. The phase III ADVANCE CAPACITY study (NCT04084678) seeks to evaluate 193 subjects with PAH, randomized between oral ralinepag and placebo at a 2:1 ratio, along with PAH background therapy, for 28 weeks with an optional open label extension period. The primary endpoint of the study is the change from baseline to week 28 in peak oxygen consumption (VO2) assessed by cardiopulmonary exercise testing.

ADVANCE OUTCOMES. The phase III ADVANCE OUTCOMES study (NCT03626688) seeks to evaluate approximately 700 PAH patients, randomized 1:1 between oral ralinepag and placebo along with background therapy. The primary endpoint is the time from randomization to the first adjudicated protocol-defined clinical worsening event.

Autologous cell therapy for PAH — SAPPHIRE. Conducted by our Canadian affiliate Northern Therapeutics, Inc., the phase II/III SAPPHIRE study seeks to evaluate the use of autologous endothelial progenitor cells (EPCs) transfected with human endothelial NO-synthase in patients with PAH taking conventional PAH treatments. The study seeks to enroll 45 PAH patients in one of three arms: (1) placebo for six months followed by autologous EPCs for six months; (2) autologous EPCs for six months followed by placebo for six months; and (3) autologous EPCs for twelve months. The primary endpoint is the change in 6MWD from baseline to month six.

CONFERENCE CALL

We will host a teleconference on Wednesday, April 29, 2020, at 9:00 a.m. Eastern Time. The teleconference is accessible by dialing (866) 209-9943 in the United States, with international callers dialing +1 (825) 312-2282. A rebroadcast of the teleconference will be available for one week and can be accessed by dialing (800) 585-8367 in the United States, with international callers dialing +1 (416) 621-4642, and using access code: 1984097.

This teleconference will also be webcast and can be accessed via our website at View Source

FDA approves Zejula (niraparib) as the only once-daily PARP inhibitor in first-line monotherapy maintenance treatment for women with platinum-responsive advanced ovarian cancer regardless of biomarker status

On April 29, 2020 GlaxoSmithKline plc (LSE/NYSE: GSK) reported the US Food and Drug Administration (FDA) approved the company’s supplemental New Drug Application (sNDA) for Zejula (niraparib), an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor, as a monotherapy maintenance treatment for women with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy, regardless of biomarker status (Press release, GlaxoSmithKline, APR 29, 2020, View Source [SID1234556760]). Until now, only 20% of women with ovarian cancer, those with a BRCA mutation (BRCAm), were eligible to be treated with a PARP inhibitor as monotherapy in the first-line maintenance setting.[i]

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Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK, said: "Women with advanced ovarian cancer have a five-year survival rate of less than 50%. This expanded indication means that many more women with this devastating disease can receive earlier treatment with Zejula, which can extend the time it takes for their cancer to progress."

Zejula is the only once-daily PARP inhibitor approved in the US as monotherapy for women with advanced ovarian cancer beyond those with BRCAm disease in the first-line and recurrent maintenance treatment settings, as well as late-line primary treatment settings.

This new indication is supported by data from the phase III PRIMA study (ENGOT-OV26/GOG-3012), which enrolled patients with newly diagnosed advanced ovarian cancer following a complete or partial response to platinum-based chemotherapy regardless of biomarker status. The PRIMA study enrolled women who had higher risk of disease progression, a population with high unmet needs and limited treatment options.

Dr. Bradley Monk, PRIMA investigator, US Oncology, University of Arizona College of Medicine, Phoenix Creighton University School of Medicine at St. Joseph’s Hospital Phoenix, said: "PRIMA was designed for patients with ovarian cancer who have a high unmet need. The positive data observed regardless of biomarker status in this study is extremely encouraging and suggests benefit beyond the BRCAm population. This approval is an important step forward in the treatment of ovarian cancer. In my opinion, maintenance treatment with niraparib should be considered an option for appropriate patients who responded to first-line platinum-based chemotherapy versus active surveillance."

The primary endpoint in the PRIMA study was progression-free survival (PFS) analysed sequentially, first in the homologous recombination deficient (HRd) population, then in the overall population. The PRIMA study significantly improved PFS for patients treated with Zejula, regardless of biomarker status. In the HRd population, Zejula resulted in a 57% reduction in the risk of disease progression or death vs. placebo (HR 0.43; 95% CI, 0.31 to 0.59; p<0.0001), and a 38% reduction in the risk of disease progression or death vs. placebo in the overall population (HR 0.62; 95% CI, 0.50 to 0.76; p<0.0001).

Zejula’s safety profile, as demonstrated by the PRIMA results, was consistent with clinical trial experience. The most common grade 3 or higher adverse events with Zejula included thrombocytopenia (39%), anaemia (31%) and neutropenia (21%).

At initiation of the PRIMA study, patients received a fixed starting dose of 300 mg of Zejula once-daily. The study was later amended to incorporate an individualised starting dose of either 200 mg or 300 mg of Zejula once-daily based on the patient’s baseline weight and/or platelet count. Lower rates of grade 3 and 4 haematologic treatment-emergent adverse events were observed with an individualised starting dose, compared to the overall population, including thrombocytopenia (21% compared to 39%), anaemia (23% compared to 31%) and neutropenia (15% compared to 21%).

The Zejula US prescribing information has been updated to include the individualised starting dose of 200 mg or 300 mg once-daily based on patients’ baseline weight and/or platelet count for the first-line maintenance treatment indication. The starting dose for recurrent ovarian cancer and late-line treatment settings is 300 mg once-daily.

"It’s so important for patients with ovarian cancer to have treatment options, and this approval is positive news for our community," said Audra Moran, President and CEO, Ovarian Cancer Research Alliance. "PARP inhibitors represent a major advancement in the fight against ovarian cancer, and having a new first-line maintenance option for platinum-responsive advanced ovarian cancer patients — regardless of BRCA mutation status — is especially exciting. We are determined to keep funding research and partnering with scientists who are on the frontline of finding new treatments like this one to help those impacted by this disease."

PRIMA study results were previously presented at the 2019 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and published in the New England Journal of Medicine.

Zejula is not approved for use in first-line maintenance treatment outside the US.

About Ovarian Cancer
In the US, ovarian cancer impacts nearly 222,000 women annually,[ii] and it is the fifth most frequent cause of cancer death among women.[iii] Despite high response rates to platinum-based chemotherapy in the front-line setting, approximately 85% of patients will experience disease recurrence.[iv] Once the disease recurs, it is rarely curable, with decreasing time intervals to each subsequent recurrence.

About Zejula (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 programme by assessing activity across multiple tumour types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development programme for niraparib includes several combination studies, including a phase III study as a first-line triplet maintenance treatment in ovarian cancer (FIRST).

GSK in Oncology
GSK is focused on maximising 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 utilising modalities such as small molecules, antibodies, antibody drug conjugates and cell therapy, either alone or in combination.

Indications and Important Safety Information for ZEJULA
Indications

ZEJULA is indicated:

for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy.
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.
for the treatment of adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer 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:
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.
Select patients for therapy based on an FDA-approved companion diagnostic for ZEJULA.

Important Safety Information

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including some fatal cases, was reported in 15 patients (0.8%) out of 1785 patients treated with ZEJULA monotherapy in clinical trials. The duration of therapy in patients who developed secondary MDS/cancer therapy-related AML varied from 0.5 months to 4.9 years. These patients had received prior chemotherapy with platinum agents and/or other DNA-damaging agents including radiotherapy. Discontinue ZEJULA if MDS/AML is confirmed.

Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients receiving ZEJULA. The overall incidence of Grade ≥3 thrombocytopenia, anemia and neutropenia were reported, respectively, in 39%, 31%, and 21% of patients receiving ZEJULA in PRIMA; 29%, 25%, and 20% of patients receiving ZEJULA in NOVA; and 28%, 27%, and 13% of patients receiving ZEJULA in QUADRA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 4%, 2%, and 2% of patients in PRIMA; 3%, 1%, and 2% of patients in NOVA; and 4%, 2%, and 1% of patients in QUADRA. In patients who were administered a starting dose of ZEJULA based on baseline weight or platelet count in PRIMA, Grade ≥3 thrombocytopenia, anemia and neutropenia were reported, respectively, in 22%, 23%, and 15% of patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 3%, 3%, and 2% of patients. Do not start ZEJULA until patients have recovered from hematological toxicity caused by prior chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months, and periodically thereafter. If hematological toxicities do not resolve within 28 days following interruption, discontinue ZEJULA, and refer the patient to a hematologist for further investigations.

Hypertension and hypertensive crisis have been reported in patients receiving ZEJULA. Grade 3-4 hypertension occurred in 6% of patients receiving ZEJULA vs 1% of patients receiving placebo in PRIMA, with no reported discontinuations. Grade 3-4 hypertension occurred in 9% of patients receiving ZEJULA vs 2% of patients receiving placebo in NOVA, with discontinuation occurring in <1% of patients. Grade 3-4 hypertension occurred in 5% of ZEJULA-treated patients in QUADRA, with discontinuation occurring in <0.2% of patients. Monitor blood pressure and heart rate at least weekly for the first two months, then monthly for the first year, and periodically thereafter during treatment. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Manage hypertension with antihypertensive medications and adjustment of the ZEJULA dose, if necessary.

Embryo-Fetal Toxicity and Lactation: Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months after receiving their final dose of ZEJULA. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women to not breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose.

First-line Maintenance Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of all patients who received ZEJULA in PRIMA were thrombocytopenia (66%), anemia (64%), nausea (57%), fatigue (51%), neutropenia (42%), constipation (40%), musculoskeletal pain (39%), leukopenia (28%), headache (26%), insomnia (25%), vomiting (22%), dyspnea (22%), decreased appetite (19%), dizziness (19%), cough (18%), hypertension (18%), AST/ALT elevation (14%), and acute kidney injury (12%).

Common lab abnormalities (Grades 1-4) in ≥25% of all patients who received ZEJULA in PRIMA included: decreased hemoglobin (87%), decreased platelets (74%), decreased leukocytes (71%), increased glucose (66%), decreased neutrophils (66%), decreased lymphocytes (51%), increased alkaline phosphatase (46%), increased creatinine (40%), decreased magnesium (36%), increased AST (35%) and increased ALT (29%).

Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received ZEJULA in NOVA were nausea (74%), thrombocytopenia (61%), fatigue/asthenia (57%), anemia (50%), constipation (40%), vomiting (34%), neutropenia (30%), insomnia (27%), headache (26%), decreased appetite (25%), nasopharyngitis (23%), rash (21%), hypertension (20%), dyspnea (20%), mucositis/stomatitis (20%), dizziness (18%), back pain (18%), dyspepsia (18%), leukopenia (17%), cough (16%), urinary tract infection (13%), anxiety (11%), dry mouth (10%), AST/ALT elevation (10%), dysgeusia (10%), palpitations (10%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients who received ZEJULA in NOVA included: decrease in hemoglobin (85%), decrease in platelet count (72%), decrease in white blood cell count (66%), decrease in absolute neutrophil count (53%), increase in AST (36%) and increase in ALT (28%).

Treatment of Advanced HRD+ Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received ZEJULA in QUADRA were nausea (67%), fatigue (56%), thrombocytopenia (52%), anemia (51%), vomiting (44%), constipation (36%), abdominal pain (34%), musculoskeletal pain (29%), decreased appetite (27%), dyspnea (22%), insomnia (21%), neutropenia (20%), headache (19%), diarrhea (17%), acute kidney injury (17%), urinary tract infection (15%), hypertension (14%), cough (13%), dizziness (11%), AST/ALT elevation (11%), blood alkaline phosphatase increased (11%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients who received ZEJULA in QUADRA included: decreased hemoglobin (83%), increased glucose (66%), decreased platelets (60%), decreased lymphocytes (57%), decreased leukocytes (53%), decreased magnesium (46%), increased alkaline phosphatase (40%), increased gamma glutamyl transferase (40%), increased creatinine (36%), decreased sodium (34%), decreased neutrophils (34%), increased aspartate aminotransferase (29%), and decreased albumin (27%).