GD2 inhibitors(Disialoganglioside GD2 inhibitors), ADCC(Antibody-dependent cell-mediated cytotoxicity (ADCC) effects), Complement dependent cytotoxicity (CDC) effects

Therapeutic Areas

NeoplasmsOther DiseasesRespiratory Diseases+ [1]

Active Indication

NeuroblastomaGanglioneuroblastomaNeuroblastoma recurrent+ [5]

Inactive Indication

Small cell lung cancer recurrent

Originator Organization

National Cancer Institute

Active Organization

National Cancer Institute

United Therapeutics Corp.

Ohara Pharmaceutical Co., Ltd.

Inactive Organization

United Therapeutics Europe Ltd.

Drug Highest PhaseApproved

First Approval Date

US (10 Mar 2015),

Neuroblastoma

RegulationOrphan Drug (US), Overseas New Drugs Urgently Needed in Clinical Settings (CN)

Gene Sequence

Sequence Code 263366044H

Source: *****

Sequence Code 263366046L

Source: *****

Clinical Trials associated with Dinutuximab

NCT06450041 / Not yet recruitingPhase 2IIT

Phase II Study of Ex-Vivo Expanded Allogeneic Universal Donor TGFβi NK Cell Infusions in Combination With Temozolomide, Irinotecan, Dinutuximab, and Sargramostim in Patients With Relapsed or Refractory Neuroblastoma The STING (Sequential Temozolomide, Irinotecan, NK Cells and GD2 mAb) Trial

This is a phase II study looking at patient response to treatment with the combination dinutuximab, temozolomide, irinotecan, and GM-CSF.

Start Date01 Sep 2024

Sponsor / Collaborator

United Therapeutics Corp.

[+1]

NCT06172296 / RecruitingPhase 3IIT

A Phase 3 Study of Dinutuximab Added to Intensive Multimodal Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma

This phase III trial tests how well the addition of dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy works for treating children with newly diagnosed high-risk neuroblastoma. Dinutuximab is a monoclonal antibody that binds to a molecule called GD2, which is found on the surface of neuroblastoma cells, but is not present on many healthy or normal cells in the body. When dinutuximab binds to the neuroblastoma cells, it helps signal the immune system to kill the tumor cells. This helps the cells of the immune system kill the cancer cells, this is a type of immunotherapy. When chemotherapy and immunotherapy are given together, during the same treatment cycle, it is called chemoimmunotherapy. This clinical trial randomly assigns patients to receive either standard chemotherapy and surgery or chemoimmunotherapy (chemotherapy plus dinutuximab) and surgery during Induction therapy. Chemotherapy drugs administered during Induction include, cyclophosphamide, topotecan, cisplatin, etoposide, vincristine, and doxorubicin. These drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Upon completion of 5 cycles of Induction therapy, a disease evaluation is completed to determine how well the treatment worked. If the tumor responds to therapy, patients receive a tandem transplantation with stem cell rescue. If the tumor has little improvement or worsens, patients receive chemoimmunotherapy on Extended Induction. During Extended Induction, dinutuximab is given with irinotecan, temozolomide. Patients with a good response to therapy move on to Consolidation therapy, when very high doses of chemotherapy are given at two separate points to kill any remaining cancer cells. Following, transplant, radiation therapy is given to the site where the cancer originated (primary site) and to any other areas that are still active at the end of Induction. The final stage of therapy is Post-Consolidation. During Post-Consolidation, dinutuximab is given with isotretinoin, with the goal of maintaining the response achieved with the previous therapy. Adding dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy may be better at treating children with newly diagnosed high-risk neuroblastoma.

Start Date19 Apr 2024

Sponsor / Collaborator

National Cancer Institute

NCT05400603 / RecruitingPhase 1IIT

A Phase I Study of Allogeneic Ex Vivo Expanded Gamma Delta (γδ) T Cells in Combination With Dinutuximab, Temozolomide, Irinotecan, and Zoledronate in Children With Refractory/ Relapsed, or Progressive Neuroblastoma or Refractory/ Relapsed Osteosarcoma

The goal of this clinical trial is to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of allogeneic expanded γδ T cells when delivered with Dinutuximab, temozolomide, irinotecan, and zoledronate in children with refractory or recurrent neuroblastoma or refractory/ relapsed osteosarcoma as well as to define the toxicities of allogeneic expanded γδ T cells when delivered with Dinutuximab, temozolomide, irinotecan, and zoledronate

Start Date06 Nov 2023

Sponsor / Collaborator

Emory University

100 Clinical Results associated with Dinutuximab

100 Translational Medicine associated with Dinutuximab

100 Patents (Medical) associated with Dinutuximab

257

Literatures (Medical) associated with Dinutuximab

01 Nov 2024·Cancer Genomics & Proteomics

GD2 in Breast Cancer: A Potential Biomarker and Therapeutic Target

Review

Author: Mokbel, Kefah ; MOKBEL, KEFAH

Expression of disialoganglioside GD2 in normal tissues is primarily limited to the central nervous system, peripheral sensory nerve fibers, dermal melanocytes, lymphocytes, and mesenchymal stem cells. Its widespread overexpression in various cancer types allows it to be classified as a tumor-associated antigen with potential diagnostic and therapeutic implications. This article reviews the synthesis pathways of GD2 and its role in cancer cell adhesion, proliferation, and metastasis with a focus on breast cancer. GD2 appears to be overexpressed on the outer membrane of most breast cancer cells and breast cancer stem cells (BCSCs) and is closely linked to epithelial-mesenchymal transition (EMT). GD3 synthase (GD3S) is considered to be the rate-determining step in GD2 synthesis. Clinical studies indicate that GD2 expression is increased in 35-70% of breast cancer samples, with higher levels in triple-negative breast cancer (TNBC). This overexpression correlates with more aggressive tumor features and worse prognosis. Therapeutic targeting of GD2 with monoclonal antibodies (moABs) like dinutuximab and naxitamab has demonstrated anti-cancer activity in preclinical cancer models and human clinical trials against high-risk neuroblastoma reducing tumor growth and enhancing survival. GD2-specific chimeric antigen receptor (CAR) T-cell therapy and GD3S inhibition present other promising therapeutic strategies to improve clinical outcomes. Furthermore, GD2-targeted vaccines are currently being investigated in cancer therapy. This narrative review article underscores the critical role of GD2 in breast cancer pathogenesis and highlights the promising therapeutic opportunities it offers. It advocates for the initiation of clinical trials to further explore the potential of GD2-targeted treatment in combination with standard breast cancer therapies.

01 May 2024·Journal for ImmunoTherapy of Cancer

Enhancing IgA-mediated neutrophil cytotoxicity against neuroblastoma by CD47 blockade

Article

Author: Leusen, Jeanette ; van Tetering, Geert ; Jansen, Marco ; Wienke, Judith ; Stip, Marjolein ; Passchier, Elsemieke ; Nederend, Maaike ; van den Ham, Femke ; Chan, Chilam

Background:

Approximately half of the neuroblastoma patients develop high-risk neuroblastoma. Current treatment involves a multimodal strategy, including immunotherapy with dinutuximab (IgG ch14.18) targeting GD2. Despite achieving promising results, the recurrence rate remains high and poor survival persists. The therapeutic efficacy of dinutuximab is compromised by suboptimal activation of neutrophils and severe neuropathic pain, partially induced by complement activation.

Methods:

To enhance neutrophil cytotoxicity, IgG ch14.18 was converted to the IgA isotype, resulting in potent neutrophil-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), without complement activation. However, myeloid checkpoint molecules hamper neutrophil cytotoxicity, for example through CD47 that is overexpressed on neuroblastomas and orchestrates an immunosuppressive environment upon ligation to signal regulatory protein alpha (SIRPα) expressed on neutrophils. In this study, we combined IgA therapy with CD47 blockade.

Results:

In vitro killing assays showed enhanced IgA-mediated ADCC by neutrophils targeting neuroblastoma cell lines and organoids in comparison to IgG. Notably, when combined with CD47 blockade, both IgG and IgA therapy were enhanced, though the combination with IgA resulted in the greatest improvement of ADCC. Furthermore, in a neuroblastoma xenograft model, we systemically blocked CD47 with a SIRPα fusion protein containing an ablated IgG1 Fc, and compared IgA therapy to IgG therapy. Only IgA therapy combined with CD47 blockade increased neutrophil influx to the tumor microenvironment. Moreover, the IgA combination strategy hampered tumor outgrowth most effectively and prolonged tumor-specific survival.

Conclusion:

These promising results highlight the potential to enhance immunotherapy efficacy against high-risk neuroblastoma through improved neutrophil cytotoxicity by combining IgA therapy with CD47 blockade.

15 Apr 2024·International journal of cancer

GM‐CSF, G‐CSF or no cytokine therapy with anti‐GD2 immunotherapy for high‐risk neuroblastoma

Review

Author: Ragsdale, Carolyn E ; Kinsey, Joyce ; Mora, Jaume ; Modak, Shakeel ; Lazarus, Hillard M

Abstract:

Colony‐stimulating factors have been shown to improve anti‐disialoganglioside 2 (anti‐GD2) monoclonal antibody response in high‐risk neuroblastoma by enhancing antibody‐dependent cell‐mediated cytotoxicity (ADCC). A substantial amount of research has focused on recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) as an adjuvant to anti‐GD2 monoclonal antibodies. There may be a disparity in care among patients as access to GM‐CSF therapy and anti‐GD2 monoclonal antibodies is not uniform. Only select countries have approved these agents for use, and even with regulatory approvals, access to these agents can be complex and cost prohibitive. This comprehensive review summarizes clinical data regarding efficacy and safety of GM‐CSF, recombinant human granulocyte colony‐stimulating factor (G‐CSF) or no cytokine in combination with anti‐GD2 monoclonal antibodies (ie, dinutuximab, dinutuximab beta or naxitamab) for immunotherapy of patients with high‐risk neuroblastoma. A substantial body of clinical data support the immunotherapy combination of anti‐GD2 monoclonal antibodies and GM‐CSF. In contrast, clinical data supporting the use of G‐CSF are limited. No formal comparison between GM‐CSF, G‐CSF and no cytokine has been identified. The treatment of high‐risk neuroblastoma with anti‐GD2 therapy plus GM‐CSF is well established. Suboptimal efficacy outcomes with G‐CSF raise concerns about its suitability as an alternative to GM‐CSF as an adjuvant in immunotherapy for patients with high‐risk neuroblastoma. While programs exist to facilitate obtaining GM‐CSF and anti‐GD2 monoclonal antibodies in regions where they are not commercially available, continued work is needed to ensure equitable therapeutic options are available globally.

News (Medical) associated with Dinutuximab

31 Jul 2024

·www.businesswire.com

United Therapeutics Corporation Reports Second Quarter 2024 Financial Results

SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.--( BUSINESS WIRE )--United Therapeutics Corporation (Nasdaq: UTHR ), a public benefit corporation, today announced its financial results for the quarter ended June 30, 2024. Total revenues in the second quarter of 2024 grew 20 percent year-over-year to $714.9 million, compared to $596.5 million in the second quarter of 2023. “This quarter we drove record revenue from our foundational commercial business. Next year we expect data from our innovative clinical pipeline. All this while we march forward with our revolutionary organ manufacturing programs,” said Martine Rothblatt, Ph.D. , Chairperson and Chief Executive Officer of United Therapeutics. “We believe there is no other biotech with our combination of relentless focus, near-term commercial growth, and clinical potential.” Michael Benkowitz , President and Chief Operating Officer of United Therapeutics, added, “Our fifth straight quarter of record revenue was driven by continued traction for Tyvaso in pulmonary hypertension associated with interstitial lung disease, along with strong fundamentals for our other products in pulmonary arterial hypertension and neuroblastoma.” Second Quarter 2024 Financial Results Key financial highlights include (dollars in millions, except per share data): Three Months Ended June 30, Dollar Change Percentage Change 2024 2023 Total revenues $ 714.9 $ 596.5 $ 118.4 20 % Net income $ 278.1 $ 259.2 $ 18.9 7 % Net income, per basic share $ 6.26 $ 5.53 $ 0.73 13 % Net income, per diluted share $ 5.85 $ 5.24 $ 0.61 12 % Revenues The table below presents the components of total revenues (dollars in millions): Three Months Ended June 30, Dollar Change Percentage Change 2024 2023 Net product sales: Tyvaso DPI ®(1) $ 258.3 $ 193.6 $ 64.7 33 % Nebulized Tyvaso ®(1) 139.9 125.3 14.6 12 % Total Tyvaso 398.2 318.9 79.3 25 % Remodulin ®(2) 147.3 127.2 20.1 16 % Orenitram ® 107.1 95.1 12.0 13 % Unituxin ® 51.7 44.3 7.4 17 % Adcirca ® 5.7 7.5 (1.8 ) (24 )% Other 4.9 3.5 1.4 40 % Total revenues $ 714.9 $ 596.5 $ 118.4 20 % (1) Net product sales include both the drug product and the respective inhalation device. (2) Net product sales include sales of infusion devices, including the Remunity ® Pump. Total Tyvaso revenues grew by 25 percent to $398.2 million in the second quarter of 2024, compared to $318.9 million in the second quarter of 2023. This growth was primarily due to an increase in quantities sold, driven by the commercial launch of Tyvaso DPI in June 2022 and continued growth in commercial utilization by patients with pulmonary hypertension associated with interstitial lung disease and, to a lesser extent, price increases. The growth in Tyvaso DPI revenues resulted primarily from an increase in quantities sold and, to a lesser extent, price increases. The increase in Tyvaso DPI quantities sold was due to continued growth in the number of patients following the product’s launch and, to a lesser extent, increased commercial utilization following the implementation of the Part D redesign under the Inflation Reduction Act ( IRA ). The growth in Remodulin revenues resulted primarily from an increase in U.S. Remodulin revenues, driven by an increase in quantities sold and, to a lesser extent, lower Medicaid rebates. The growth in Orenitram revenues resulted primarily from an increase in quantities sold and, to a lesser extent, a price increase. The increase in quantities sold was driven, at least in part, by increased commercial utilization following the implementation of the Part D redesign under the IRA. The growth in Unituxin revenues resulted from a price increase and an increase in quantities sold. The table below presents the breakdown of total revenues between the United States and rest-of-world ( ROW ) (in millions): Three Months Ended June 30, 2024 2023 U.S. ROW Total U.S. ROW Total Net product sales: Tyvaso DPI (1) $ 258.3 $ — $ 258.3 $ 193.6 $ — $ 193.6 Nebulized Tyvaso (1) 130.2 9.7 139.9 119.6 5.7 125.3 Total Tyvaso 388.5 9.7 398.2 313.2 5.7 318.9 Remodulin (2) 122.5 24.8 147.3 103.5 23.7 127.2 Orenitram 107.1 — 107.1 95.1 — 95.1 Unituxin 46.8 4.9 51.7 39.5 4.8 44.3 Adcirca 5.7 — 5.7 7.5 — 7.5 Other 4.6 0.3 4.9 3.2 0.3 3.5 Total revenues $ 675.2 $ 39.7 $ 714.9 $ 562.0 $ 34.5 $ 596.5 (1) Net product sales include both the drug product and the respective inhalation device. (2) Net product sales include sales of infusion devices, including the Remunity Pump. Expenses Cost of sales. The table below summarizes cost of sales by major category (dollars in millions): Three Months Ended June 30, Dollar Change Percentage Change 2024 2023 Category: Cost of sales $ 75.9 $ 63.2 $ 12.7 20 % Share-based compensation expense (1) 1.9 0.9 1.0 111 % Total cost of sales $ 77.8 $ 64.1 $ 13.7 21 % (1) See Share-based compensation below. Cost of sales, excluding share-based compensation. Cost of sales for the three months ended June 30, 2024 increased as compared to the same period in 2023, primarily due to an increase in Tyvaso DPI royalty expense. Research and development. The table below summarizes the nature of research and development expense by major expense category (dollars in millions): Three Months Ended June 30, Dollar Change Percentage Change 2024 2023 Category: External research and development (1) $ 49.4 $ 49.3 $ 0.1 — % Internal research and development (2) 44.5 34.7 9.8 28 % Share-based compensation expense (3) 8.6 5.0 3.6 72 % Impairments (4) — — — — % Other (5) 37.1 — 37.1 NM (6) Total research and development expense $ 139.6 $ 89.0 $ 50.6 57 % (1) External research and development primarily includes fees paid to third parties (such as clinical trial sites, contract research organizations, and contract laboratories) for preclinical and clinical studies and payments to third-party contract manufacturers before FDA approval of the relevant product. (2) Internal research and development primarily includes salary-related expenses for research and development functions, internal costs to manufacture product candidates before FDA approval, and internal facilities-related expenses, including depreciation, related to research and development activities. (3) See Share-based compensation below. (4) Impairments primarily includes impairment charges to write down the carrying value of in-process research and development and of certain property, plant, and equipment as a result of research and development activities. There were no impairment charges during the three months ended June 30, 2024 and June 30, 2023. (5) Other primarily includes upfront fees and milestone payments to third parties under license agreements related to development-stage products and adjustments to the fair value of our contingent consideration obligations. (6) Calculation is not meaningful. Research and development, excluding share-based compensation. Research and development expense for the three months ended June 30, 2024 increased as compared to the same period in 2023, primarily due to increased expenditures related to upfront non-refundable licensing payments for drug delivery devices and increased expenditures related to organ manufacturing projects. Selling, general, and administrative. The table below summarizes selling, general, and administrative expense by major category (dollars in millions): Three Months Ended June 30, Dollar Change Percentage Change 2024 2023 Category: General and administrative $ 113.0 $ 102.0 $ 11.0 11 % Sales and marketing 25.4 20.1 5.3 26 % Share-based compensation expense (1) 39.2 7.9 31.3 396 % Total selling, general, and administrative expense $ 177.6 $ 130.0 $ 47.6 37 % (1) See Share-based compensation below. General and administrative, excluding share-based compensation . General and administrative expense for the three months ended June 30, 2024 increased as compared to the same period in 2023, primarily due to an increase in legal expenses related to litigation matters and an increase in personnel expense due to growth in headcount. Share-based compensation. The table below summarizes share-based compensation expense by major category (dollars in millions): Three Months Ended June 30, Dollar Change Percentage Change 2024 2023 Category: Stock options $ 8.1 $ 1.6 $ 6.5 406 % Restricted stock units 19.2 13.6 5.6 41 % Share tracking awards plan ( STAP ) 21.9 (1.9 ) 23.8 NM (1) Employee stock purchase plan 0.5 0.5 — — % Total share-based compensation expense $ 49.7 $ 13.8 $ 35.9 260 % (1) Calculation is not meaningful. The increase in share-based compensation expense for the three months ended June 30, 2024, as compared to the same period in 2023, was primarily due to an increase in STAP expense driven by a 39 percent increase in our stock price for the three months ended June 30, 2024, as compared to a one percent decrease in our stock price for the same period in 2023. Income tax expense. Income tax expense for the three months ended June 30, 2024 and 2023 was $77.2 million and $76.0 million, respectively. Our effective income tax rate ( ETR ) for the three months ended June 30, 2024 and 2023 was 22 percent and 23 percent, respectively. Our ETR for the three months ended June 30, 2024 decreased compared to our ETR for the three months ended June 30, 2023 primarily due to a lower amount of uncertain tax positions recorded. Share repurchase. In March 2024, we entered into an accelerated share repurchase agreement (the ASR agreement ) with Citibank, N.A. ( Citi ). Under the ASR agreement, we made an aggregate upfront payment of $1.0 billion to Citi and received an aggregate initial delivery of 3,275,199 shares of our common stock on March 27, 2024, representing approximately 80 percent of the total shares that would be repurchased under the ASR agreement measured based on the closing price of our common stock on March 25, 2024. The share purchase under the ASR agreement was divided into two tranches, resulting in upfront payments of $300 million and $700 million, respectively. The final settlement of the $300 million tranche occurred in June 2024, and we received an additional 181,772 shares of our common stock upon settlement. At the final settlement of the $700 million second tranche, which we expect to occur in the third quarter of 2024, we may be entitled to receive additional shares of common stock, or, under certain limited circumstances, be required to make a cash payment to Citi or, if we so elect, deliver shares of common stock to Citi. The final number of shares that we will ultimately repurchase pursuant to the ASR agreement will be based on the average of the daily volume-weighted average price per share of our common stock during the repurchase period, less a discount and subject to adjustments pursuant to the terms and conditions of the ASR agreement. Webcast We will host a webcast to discuss our second quarter 2024 financial results on Wednesday, July 31, 2024, at 9:00 a.m. Eastern Time. The webcast can be accessed live via our website at https://ir.unither.com/events-and-presentations . A replay of the webcast will also be available at the same location on our website. United Therapeutics: Enabling Inspiration At United Therapeutics, our vision and mission are one. We use our enthusiasm, creativity, and persistence to innovate for the unmet medical needs of our patients and to benefit our other stakeholders. We are bold and unconventional. We have fun; we do good. We are the first publicly-traded biotech or pharmaceutical company to take the form of a public benefit corporation ( PBC ). Our public benefit purpose is to provide a brighter future for patients through (a) the development of novel pharmaceutical therapies; and (b) technologies that expand the availability of transplantable organs . You can learn more about what it means to be a PBC here: unither.com/pbc . Forward-Looking Statements Statements included in this press release that are not historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, statements related to our anticipated near-term commercial growth; the anticipated progress of our organ manufacturing programs; our clinical potential, including anticipated clinical trial data next year; our unique position in the biotech industry; and our goals of innovating for the unmet medical needs of our patients and to benefit our other stakeholders, furthering our public benefit purpose of developing novel pharmaceutical therapies and technologies that expand the availability of transplantable organs. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the Securities and Exchange Commission, that could cause actual results to differ materially from anticipated results. Consequently, such forward-looking statements are qualified by the cautionary statements, cautionary language and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We are providing this information as of July 31, 2024, and assume no obligation to update or revise the information contained in this press release whether as a result of new information, future events, or any other reason. ORENITRAM, REMODULIN, REMUNITY, TYVASO, TYVASO DPI, and UNITUXIN are registered trademarks of United Therapeutics Corporation and/or its subsidiaries. ADCIRCA is a registered trademark of Eli Lilly and Company. UNITED THERAPEUTICS CORPORATION CONSOLIDATED STATEMENTS OF OPERATIONS (In millions, except per share data) Three Months Ended June 30, 2024 2023 (Unaudited) Total revenues $ 714.9 $ 596.5 Operating expenses: Cost of sales 77.8 64.1 Research and development 139.6 89.0 Selling, general, and administrative 177.6 130.0 Total operating expenses 395.0 283.1 Operating income 319.9 313.4 Interest income 46.2 37.2 Interest expense (11.6 ) (14.8 ) Other income (expense), net 0.8 (0.6 ) Total other income, net 35.4 21.8 Income before income taxes 355.3 335.2 Income tax expense (77.2 ) (76.0 ) Net income $ 278.1 $ 259.2 Net income per common share: Basic $ 6.26 $ 5.53 Diluted $ 5.85 $ 5.24 Weighted average number of common shares outstanding: Basic 44.4 46.9 Diluted 47.5 49.5 SELECTED CONSOLIDATED BALANCE SHEET DATA (Unaudited, in millions) June 30, 2024 Cash, cash equivalents, and marketable investments $ 4,301.9 Total assets 6,723.2 Total liabilities 1,026.0 Total stockholders’ equity 5,697.2 Category: Earnings

Financial Statement

15 Apr 2024

·www.prnewswire.com

Norgine B.V. submits Marketing Authorisation Application via Project Orbis for eflornithine (difluoromethylornithine [DFMO]) in high-risk neuroblastoma

AMSTERDAM, April 15, 2024 /PRNewswire/ -- Norgine B.V. today announced its first marketing authorisation application submissions on 10 April 2024, seeking approval for eflornithine in high-risk neuroblastoma (HRNB), via Project Orbis in Australia, Switzerland and the United Kingdom. This milestone supports Norgine's efforts to deliver patient access to eflornithine and bring a further treatment option in the field of paediatric oncology. Norgine and USWM, LLC (dba US WorldMeds), a Kentucky-based specialty pharmaceutical company, have an exclusive licensing agreement by which Norgine will register and commercialise eflornithine, also referred to as DFMO, in Europe, Australia and New Zealand. On 13 December 2023, the US Food and Drug Administration (FDA) approved eflornithine as the first oral maintenance therapy for high-risk neuroblastoma (HRNB), indicated to reduce the risk of relapse in adult and paediatric patients who have received certain prior therapies.1 The approval decision was based on findings from a trial comparing outcomes from Study 3b (NCT02395666; investigational arm)2,4 and Study ANBL0032 (NCT00026312; clinical-trial-derived external control arm)3,4, where use of eflornithine resulted in improved event-free survival and overall survival when compared to outcomes for patients with high-risk neuroblastoma treated with the standard of care (SoC) without the drug.1 Dr David Gillen, Chief Medical Officer at Norgine, added, "These submissions via Project Orbis represent an important first step in the regulatory process for eflornithine and re-emphasise Norgine's passion and commitment in attempting to secure additional treatment options for patients living with HRNB, a condition with a high level of unmet medical need." Follow @norgine Notes to Editors: Project Orbis Project Orbis is an initiative (since May 2019) of the US FDA Oncology Center of Excellence (OCE) and provides a framework for concurrent submission and collaborative review of innovative oncology products among international regulatory authorities. It was created with the overarching goal to speed worldwide patient access to innovative cancer therapies. Project Orbis is coordinated by the FDA, and its partners include United Kingdom Medicines and Healthcare Products regulatory Agency (UK MHRA), Australia Therapeutic Goods Administration (TGA), Canada (Health Canada), Singapore (Health Sciences Authority (HSA), Switzerland (Swissmedic), Brazil (Agência Nacional de Vigilância Sanitária (ANVISA), Israel (Ministry of Health). HRNB background Children diagnosed with HRNB undergo an intense SoC regimen that still leaves them vulnerable to relapse and death, a risk that is particularly acute during the first two years.5 Approximately 30% of patients who attain remission following upfront therapy will relapse, resulting in a poor prognosis and low likelihood of long-term survival (e.g. estimates as low as 15% of patients will live for five years after relapsing).6 Avoiding relapse is key to long-term survival, yet outside of the United States there are no approved therapies for sustaining remission following SoC treatment. The data with eflornithine demonstrate using it as maintenance therapy extends remission and reduces risk of relapse in patients with HRNB. About Norgine Norgine is a leading European specialist pharmaceutical company that has been bringing transformative medicines to patients for over a century. Our commitment to transforming people's lives drives everything we do, and our European experience, fully integrated infrastructure and exceptional partnership approach enable us to quickly apply creative solutions to bring life-changing medicines to patients that they may not otherwise be able to access. Norgine is proud to have helped more than 25 million patients around the world in 2022 and generated €530 million in net product sales, a growth of nearly 5% over 2021. Norgine has a direct presence in 16 European countries, as well as Australia and New Zealand. We also have a strong global network of partnerships in non-Norgine markets. We are a flexible and fully integrated pharmaceutical business, with manufacturing (Hengoed, Wales and Dreux, France), third party supply networks and significant product development capabilities, in addition to our sales and marketing infrastructure. This enables us to acquire, develop and commercialise specialist and innovative products that make a real difference to the lives of patients around the world. NORGINE and the sail logo are trademarks of the Norgine group of companies. References FDA approves eflornithine for adult and pediatric patients with high-risk neuroblastoma. FDA. News release. 13 December 2023. Available from: FDA approves eflornithine for adult and pediatric patients with high-risk neuroblastoma | FDA Clinical Trial NCT02395666; Preventative trial of difluoromethylornithine (DFMO) in high risk patients with neuroblastoma that is in remission. Available from: Study Details | Preventative Trial of Difluoromethylornithine (DFMO) in High Risk Patients With Neuroblastoma That is in Remission | ClinicalTrials.gov. Clinical Trial NCT00026312; Isotretinoin with or without dinutuximab, aldesleukin, and sargramostim following stem cell transplant in treating patients with neuroblastoma. Available from: Study Details | Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma | ClinicalTrials.gov Oesterheld J, Ferguson W, Kraveka JM, Bergendahl G, Clinch T, Lorenzi E et al. Eflornithine as Postimmunotherapy Maintenance in High-Risk Neuroblastoma: Externally Controlled, Propensity Score-Matched Survival Outcome Comparisons. 2024; 42 (1): 90-102. Basta NO, Halliday GC, Makin G, Birch J, Feltbower R, Bown N, et al. Factors associated with recurrence and survival length following relapse in patients with neuroblastoma. Br J Cancer. 2016;115:1048-57. London WB, Bagatell R, Weigel BJ, Fox E, Guo D, Van Ryn C, et al. Historical time to disease progression and progression-free survival in patients with recurrent/refractory neuroblastoma treated in the modern era on Children's Oncology Group early-phase trials. Cancer. 2017;123:4914-23. Logo -

License out/inDrug ApprovalClinical ResultImmunotherapy

21 Feb 2024

·www.biospace.com

United Therapeutics Corporation Reports Fourth Quarter and Full Year 2023 Financial Results

SILVER SPRING, Md. & RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)-- United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, today announced its financial results for the quarter and year ended December 31, 2023. Full year 2023 revenues rose to a record $2.33 billion, reflecting 20% growth over 2022. “Congratulations to the dedicated Unitherians who worked tirelessly to help us achieve our third straight quarter and second straight year of record revenue,” said Martine Rothblatt, Ph.D., Chairperson and Chief Executive Officer of United Therapeutics. “This represents only the beginning of our growth, driven by a strong foundation in our current commercial business and upcoming enrollment milestones for our innovative pipeline. On top of this, we have continued momentum for our revolutionary organ manufacturing programs, with the first human clinical study of a bioengineered organ, the miroliverELAP, cleared by the FDA, and the recent opening of the world’s first designated pathogen-free clinical supply facility to support our upcoming xenotransplantation clinical program.” “Our commercial business remains a solid foundation supporting our innovative and revolutionary efforts to cure end stage organ disease,” said Michael Benkowitz, President and Chief Operating Officer of United Therapeutics. “To that end, in the fourth quarter we saw record revenue for our Tyvaso business, and we achieved solid growth in our U.S. Remodulin business, with strong revenue growth and a record number of patients on therapy despite the presence of generic competition since 2019.” Fourth Quarter and Full Year 2023 Financial Results Key financial highlights include (in millions, except per share data): Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Total revenues $ 614.7 $ 491.5 $ 2,327.5 $ 1,936.3 Net income $ 217.1 $ 132.1 $ 984.8 $ 727.3 Net income, per basic share $ 4.62 $ 2.88 $ 21.04 $ 15.98 Net income, per diluted share $ 4.36 $ 2.67 $ 19.81 $ 15.00 Revenues The table below presents the components of total revenues (dollars in millions): Three Months Ended December 31, Dollar Change Percentage Change Year Ended December 31, Dollar Change Percentage Change 2023 2022 2023 2022 Net product sales: Tyvaso DPI®(1) $ 213.7 $ 92.2 $ 121.5 132% $ 731.1 $ 158.3 $ 572.8 362% Nebulized Tyvaso®(1) 136.9 150.1 (13.2) (9)% 502.6 714.7 (212.1) (30)% Total Tyvaso 350.6 242.3 108.3 45% 1,233.7 873.0 360.7 41% Remodulin®(2) 115.1 122.5 (7.4) (6)% 494.8 500.2 (5.4) (1)% Orenitram® 84.1 75.8 8.3 11% 359.4 325.1 34.3 11% Unituxin® 54.2 36.7 17.5 48% 198.9 182.9 16.0 9% Adcirca® 6.8 10.4 (3.6) (35)% 28.9 41.3 (12.4) (30)% Other 3.9 3.8 0.1 3% 11.8 13.8 (2.0) (14)% Total revenues $ 614.7 $ 491.5 $ 123.2 25% $ 2,327.5 $ 1,936.3 $ 391.2 20% (1) Net product sales include both the drug product and the respective inhalation device. (2) Net product sales include sales of infusion devices including the Remunity® Pump. Fourth Quarter 2023 Compared to Fourth Quarter 2022. Total Tyvaso revenues grew by 45% to $350.6 million in the fourth quarter of 2023, compared to $242.3 million in the fourth quarter of 2022. This growth was primarily due to an increase in quantities sold, driven by the commercial launch of Tyvaso DPI in June 2022 and continued growth in utilization by patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). The growth in Tyvaso DPI revenues resulted primarily from an increase in quantities sold. The decrease in nebulized Tyvaso revenues was primarily due to a decrease in U.S. quantities sold following the commercial launch of Tyvaso DPI, partially offset by an increase in international nebulized Tyvaso revenues, primarily due to the commercial launch of nebulized Tyvaso in Japan in December 2022, as shown in the table below. The decrease in Remodulin revenues resulted from a decrease in international Remodulin revenues, partially offset by an increase in U.S. Remodulin revenues, as shown in the table below. The increase in Orenitram revenues resulted from a price increase and an increase in quantities sold. The increase in Unituxin revenues resulted from an increase in quantities sold and a price increase. Full Year 2023 Compared to Full Year 2022. Total Tyvaso revenues grew by 41% to $1,233.7 million in 2023, compared to $873.0 million in 2022. This growth was primarily due to an increase in quantities sold, driven by the commercial launch of Tyvaso DPI in June 2022 and continued growth in utilization by patients with PH-ILD. The growth in Tyvaso DPI revenues resulted primarily from an increase in quantities sold. The decrease in nebulized Tyvaso revenues was driven by a decrease in U.S. nebulized Tyvaso revenues, primarily due to a decrease in quantities sold following the commercial launch of Tyvaso DPI, partially offset by an increase in international nebulized Tyvaso revenues, primarily due to the commercial launch of nebulized Tyvaso in Japan in December 2022, as shown in the table below. The decrease in Remodulin revenues resulted from a decrease in international Remodulin revenues, partially offset by an increase in U.S. Remodulin revenues, as shown in the table below. The increase in Orenitram revenues resulted from a price increase and an increase in quantities sold. The increase in Unituxin revenues resulted primarily from a price increase. The table below presents the breakdown of total revenues between the United States and rest-of-world (ROW) (in millions): Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 U.S. ROW Total U.S. ROW Total U.S. ROW Total U.S. ROW Total Net product sales: Tyvaso DPI(1) $ 213.7 $ — $ 213.7 $ 92.2 $ — $ 92.2 $ 731.1 $ — $ 731.1 $ 158.3 $ — $ 158.3 Nebulized Tyvaso(1) 123.7 13.2 136.9 148.4 1.7 150.1 477.1 25.5 502.6 708.6 6.1 714.7 Total Tyvaso 337.4 13.2 350.6 240.6 1.7 242.3 1,208.2 25.5 1,233.7 866.9 6.1 873.0 Remodulin(2) 106.3 8.8 115.1 97.7 24.8 122.5 414.6 80.2 494.8 407.5 92.7 500.2 Orenitram 84.1 — 84.1 75.8 — 75.8 359.4 — 359.4 325.1 — 325.1 Unituxin 48.7 5.5 54.2 36.4 0.3 36.7 181.3 17.6 198.9 170.5 12.4 182.9 Adcirca 6.8 — 6.8 10.4 — 10.4 28.9 — 28.9 41.3 — 41.3 Other 2.6 1.3 3.9 2.8 1.0 3.8 9.8 2.0 11.8 2.8 11.0 13.8 Total revenues $ 585.9 $ 28.8 $ 614.7 $ 463.7 $ 27.8 $ 491.5 $ 2,202.2 $ 125.3 $ 2,327.5 $ 1,814.1 $ 122.2 $ 1,936.3 (1) Net product sales include both the drug product and the respective inhalation device. (2) Net product sales include sales of infusion devices including the Remunity Pump. Expenses Cost of sales. The table below summarizes cost of sales by major category (dollars in millions): Three Months Ended December 31, Dollar Change Percentage Change Year Ended December 31, Dollar Change Percentage Change 2023 2022 2023 2022 Category: Cost of sales $ 70.1 $ 55.9 $ 14.2 25% $ 255.1 $ 146.7 $ 108.4 74% Share-based compensation expense(1) 0.9 2.9 (2.0) (69)% 2.4 4.9 (2.5) (51)% Total cost of sales $ 71.0 $ 58.8 $ 12.2 21% $ 257.5 $ 151.6 $ 105.9 70% (1) See Share-based compensation below. Cost of sales, excluding share-based compensation. The increase in cost of sales for the quarter ended December 31, 2023, as compared to the same period in 2022, was primarily due to an increase in Tyvaso DPI royalty expense and product costs following its commercial launch in June 2022. The increase in cost of sales for the year ended December 31, 2023, as compared to the same period in 2022, was primarily due to an increase in Tyvaso DPI royalty expense and product costs, following its commercial launch in June 2022, and an increase in Remunity product sales. Research and development expense. The table below summarizes the nature of research and development expense by major expense category (dollars in millions): Three Months Ended December 31, Dollar Change Percentage Change Year Ended December 31, Dollar Change Percentage Change 2023 2022 2023 2022 Category: External research and development(1) $ 50.4 $ 46.7 $ 3.7 8% $ 192.0 $ 168.8 $ 23.2 14% Internal research and development(2) 43.2 35.4 7.8 22% 146.6 131.4 15.2 12% Share-based compensation expense(3) 5.7 11.0 (5.3) (48)% 15.6 23.8 (8.2 ) (34)% Impairments(4) — — — —% — — — —% Other(5) 52.1 0.8 51.3 NM(6) 53.8 (1.1) 54.9 NM(6) Total research and development expense $ 151.4 $ 93.9 $ 57.5 61% $ 408.0 $ 322.9 $ 85.1 26% (1) External research and development primarily includes fees paid to third parties (such as clinical trial sites, contract research organizations, and contract laboratories) for preclinical and clinical studies and payments to third-party contract manufacturers before FDA approval of the relevant product. (2) Internal research and development primarily includes salary-related expenses for research and development functions, internal costs to manufacture product candidates before FDA approval, and internal facilities-related expenses, including depreciation, related to research and development activities. (3) See Share-based compensation below. (4) Impairments primarily includes impairment charges to write down the carrying value of in-process research and development (IPR&D) and of certain property, plant, and equipment as a result of research and development activities. There were no impairment charges during the years ended December 31, 2023 and December 31, 2022. (5) Other primarily includes upfront fees and milestone payments to third parties under license agreements related to development-stage products, adjustments to the fair value of our contingent consideration obligations, and costs to acquire certain IPR&D assets. During the quarter and year ended December 31, 2023, we recorded $46.0 million in IPR&D expense in connection with the acquisition of IVIVA Medical, Inc. (IVIVA). (6) Calculation is not meaningful. Research and development, excluding share-based compensation. The increase in research and development expense for the quarter ended December 31, 2023, as compared to the same period in 2022, was due to an increase in IPR&D expense in connection with the acquisition of IVIVA and increased expenditures related to the TETON 1 and TETON 2 clinical studies of nebulized Tyvaso in patients with idiopathic pulmonary fibrosis (IPF). The increase in research and development expense for the year ended December 31, 2023, as compared to the same period in 2022, was due to: (1) an increase in IPR&D expense in connection with the acquisition of IVIVA; (2) increased expenditures related to the TETON 1 and TETON 2 clinical studies of nebulized Tyvaso in patients with IPF; and (3) increased expenditures related to organ manufacturing projects. Selling, general, and administrative expense. The table below summarizes selling, general, and administrative expense by major category (dollars in millions): Three Months Ended December 31, Dollar Change Percentage Change Year Ended December 31, Dollar Change Percentage Change 2023 2022 2023 2022 Category: General and administrative $ 98.1 $ 89.3 $ 8.8 10% $ 374.2 $ 333.2 $ 41.0 12% Sales and marketing 24.1 23.0 1.1 5% 81.8 70.8 11.0 16% Share-based compensation expense(1) 10.0 50.9 (40.9) (80)% 21.1 78.1 (57.0) (73)% Total selling, general, and administrative expense $ 132.2 $ 163.2 $ (31.0) (19)% $ 477.1 $ 482.1 $ (5.0) (1)% (1) See Share-based compensation below. General and administrative, excluding share-based compensation. The increase in general and administrative expense for the year ended December 31, 2023, as compared to the same period in 2022, was primarily due to increases in: (1) office expenses; (2) personnel expense due to growth in headcount; and (3) sponsorships and grants. Sales and marketing, excluding share-based compensation. The increase in sales and marketing expense for the year ended December 31, 2023, as compared to the same period in 2022, was primarily due to increases in: (1) personnel expense due to growth in headcount; and (2) consulting expenses. Share-based compensation. The table below summarizes share-based compensation expense by major category (dollars in millions): Three Months Ended December 31, Dollar Change Percentage Change Year Ended December 31, Dollar Change Percentage Change 2023 2022 2023 2022 Category: Stock options $ 2.9 $ 5.8 $ (2.9) (50)% $ 15.4 $ 22.6 $ (7.2) (32)% Restricted stock units 14.1 12.1 2.0 17% 52.4 35.7 16.7 47% Share tracking awards plan (STAP) (0.9) 46.5 (47.4) (102)% (30.7 ) 46.7 (77.4) (166)% Employee stock purchase plan 0.5 0.4 0.1 25% 2.0 1.8 0.2 11% Total share-based compensation expense $ 16.6 $ 64.8 $ (48.2) (74)% $ 39.1 $ 106.8 $ (67.7) (63)% The decrease in share-based compensation expense for the quarter ended December 31, 2023, as compared to the same period in 2022, was primarily due to an increase in STAP benefit driven by a three percent decrease in our stock price during the quarter ended December 31, 2023, as compared to a 33 percent increase in our stock price for the same period in 2022. The decrease in share-based compensation expense for the year ended December 31, 2023, as compared to the same period in 2022, was primarily due to: (1) an increase in STAP benefit driven by a 21 percent decrease in our stock price during 2023, as compared to a 29 percent increase in our stock price during 2022; and (2) a decrease in stock option expense due to fewer awards remaining outstanding in 2023, as compared to the same period in 2022, partially offset by an increase in restricted stock unit expense. Other expense, net. The change in other expense, net for the year ended December 31, 2023, as compared to the same period in 2022, was primarily due to net unrealized and realized gains and losses on equity securities. Income tax expense. Income tax expense was $289.5 million for the year ended December 31, 2023, compared to $223.3 million for the same period in 2022. Our effective income tax rate was approximately 23 percent for the years ended December 31, 2023 and 2022. Inducement Restricted Stock Units On February 19, 2024, we granted a total of 11,250 restricted stock units under our 2019 Inducement Stock Incentive Plan to six newly hired employees. All of these restricted stock units will vest in full on February 19, 2027, the third anniversary of the grant date, assuming continued employment on such date, and subject to the standard terms and conditions we filed with the SEC as Exhibit 10.2 to our Current Report on Form 8-K on March 1, 2019. We are providing this information in accordance with Nasdaq Listing Rule 5635(c)(4). Webcast We will host a webcast to discuss our fourth quarter and full year 2023 financial results on Wednesday, February 21, 2024, at 9:00 a.m. Eastern Time. The webcast can be accessed live via our website at . A replay of the webcast will also be available at the same location on our website. United Therapeutics: Enabling Inspiration At United Therapeutics, our vision and mission are one. We use our enthusiasm, creativity, and persistence to innovate for the unmet medical needs of our patients and to benefit our other stakeholders. We are bold and unconventional. We have fun, we do good. We are the first publicly-traded biotech or pharmaceutical company to take the form of a public benefit corporation (PBC). Our public benefit purpose is to provide a brighter future for patients through (a) the development of novel pharmaceutical therapies; and (b) technologies that expand the availability of transplantable organs. You can learn more about what it means to be a PBC here: unither.com/pbc. Forward-Looking Statements Statements included in this press release that are not historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, statements related to our future growth expectations from both our current commercial operations and our pipeline; our organ manufacturing programs, including our efforts to cure end-stage organ disease and the anticipated clinical trials of miroliverELAP and our xenotransplantation program; and our goals of innovating for the unmet medical needs of our patients and to benefit our other stakeholders, furthering our public benefit purpose of developing novel pharmaceutical therapies and technologies that expand the availability of transplantable organs. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the Securities and Exchange Commission, that could cause actual results to differ materially from anticipated results. Consequently, such forward-looking statements are qualified by the cautionary statements, cautionary language and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We are providing this information as of February 21, 2024, and assume no obligation to update or revise the information contained in this press release whether as a result of new information, future events, or any other reason. MIROLIVERELAP, ORENITRAM, REMODULIN, REMUNITY, TYVASO, TYVASO DPI, and UNITUXIN are registered trademarks of United Therapeutics Corporation and/or its subsidiaries. ADCIRCA is a registered trademark of Eli Lilly and Company. UNITED THERAPEUTICS CORPORATION CONSOLIDATED STATEMENTS OF OPERATIONS (In millions, except per share data) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 (Unaudited) Total revenues $ 614.7 $ 491.5 $ 2,327.5 $ 1,936.3 Operating expenses: Cost of sales 71.0 58.8 257.5 151.6 Research and development 151.4 93.9 408.0 322.9 Selling, general, and administrative 132.2 163.2 477.1 482.1 Total operating expenses 354.6 315.9 1,142.6 956.6 Operating income 260.1 175.6 1,184.9 979.7 Interest income 51.0 20.8 162.7 45.2 Interest expense (15.1 ) (12.3 ) (59.3 ) (32.4 ) Other expense, net (0.6 ) (5.3 ) (14.0 ) (40.2 ) Impairment of investment in privately-held company — — — (1.7 ) Total other income (expense), net 35.3 3.2 89.4 (29.1 ) Income before income taxes 295.4 178.8 1,274.3 950.6 Income tax expense (78.3 ) (46.7 ) (289.5 ) (223.3 ) Net income $ 217.1 $ 132.1 $ 984.8 $ 727.3 Net income per common share: Basic $ 4.62 $ 2.88 $ 21.04 $ 15.98 Diluted $ 4.36 $ 2.67 $ 19.81 $ 15.00 Weighted average number of common shares outstanding: Basic 47.0 45.8 46.8 45.5 Diluted 49.8 49.4 49.7 48.5 SELECTED CONSOLIDATED BALANCE SHEET DATA (In millions) December 31, 2023 2022 Cash, cash equivalents, and marketable investments $ 4,903.9 $ 4,154.9 Total assets 7,167.0 6,044.5 Total liabilities 1,182.2 1,247.8 Total stockholders' equity 5,984.8 4,796.7 The table below presents the breakdown of select historical total revenues between the United States and ROW (in millions): Three Months Ended March 31, 2023 June 30, 2023 September 30, 2023 December 31, 2023 U.S. ROW Total U.S. ROW Total U.S. ROW Total U.S. ROW Total Net product sales: Tyvaso DPI(1) $ 118.7 $ — $ 118.7 $ 193.6 $ — $ 193.6 $ 205.1 $ — $ 205.1 $ 213.7 $ — $ 213.7 Nebulized Tyvaso(1) 115.7 4.0 119.7 119.6 5.7 125.3 118.1 2.6 120.7 123.7 13.2 136.9 Total Tyvaso 234.4 4.0 238.4 313.2 5.7 318.9 323.2 2.6 325.8 337.4 13.2 350.6 Remodulin(2) 93.2 28.2 121.4 103.5 23.7 127.2 111.6 19.5 131.1 106.3 8.8 115.1 Orenitram 88.2 — 88.2 95.1 — 95.1 92.0 — 92.0 84.1 — 84.1 Unituxin 44.3 4.8 49.1 39.5 4.8 44.3 48.8 2.5 51.3 48.7 5.5 54.2 Adcirca 7.3 — 7.3 7.5 — 7.5 7.3 — 7.3 6.8 — 6.8 Other 2.3 0.2 2.5 3.2 0.3 3.5 1.7 0.2 1.9 2.6 1.3 3.9 Total revenues $ 469.7 $ 37.2 $ 506.9 $ 562.0 $ 34.5 $ 596.5 $ 584.6 $ 24.8 $ 609.4 $ 585.9 $ 28.8 $ 614.7 Three Months Ended March 31, 2022 June 30, 2022 September 30, 2022 December 31, 2022 U.S. ROW Total U.S. ROW Total U.S. ROW Total U.S. ROW Total Net product sales: Tyvaso DPI(1) $ — $ — $ — $ 3.0 $ — $ 3.0 $ 63.1 $ — $ 63.1 $ 92.2 $ — $ 92.2 Nebulized Tyvaso(1) 170.1 1.9 172.0 196.2 1.8 198.0 193.9 0.7 194.6 148.4 1.7 150.1 Total Tyvaso 170.1 1.9 172.0 199.2 1.8 201.0 257.0 0.7 257.7 240.6 1.7 242.3 Remodulin(2) 99.1 32.6 131.7 108.5 23.5 132.0 102.2 11.8 114.0 97.7 24.8 122.5 Orenitram 82.8 — 82.8 79.0 — 79.0 87.5 — 87.5 75.8 — 75.8 Unituxin 48.0 7.6 55.6 43.3 1.2 44.5 42.8 3.3 46.1 36.4 0.3 36.7 Adcirca 9.8 — 9.8 10.4 — 10.4 10.7 — 10.7 10.4 — 10.4 Other — 10.0 10.0 — — — — — — 2.8 1.0 3.8 Total revenues $ 409.8 $ 52.1 $ 461.9 $ 440.4 $ 26.5 $ 466.9 $ 500.2 $ 15.8 $ 516.0 $ 463.7 $ 27.8 $ 491.5 Three Months Ended March 31, 2021 June 30, 2021 September 30, 2021 December 31, 2021 U.S. ROW Total U.S. ROW Total U.S. ROW Total U.S. ROW Total Net product sales: Tyvaso DPI(1) $ — $ — $ — $ — $ — $ — $ — $ — $ — $ — $ — $ — Nebulized Tyvaso(1) 122.4 0.6 123.0 152.6 1.2 153.8 160.7 3.5 164.2 165.0 1.5 166.5 Total Tyvaso 122.4 0.6 123.0 152.6 1.2 153.8 160.7 3.5 164.2 165.0 1.5 166.5 Remodulin(2) 107.1 23.1 130.2 111.0 28.8 139.8 106.8 18.6 125.4 98.5 19.8 118.3 Orenitram 72.4 — 72.4 76.2 — 76.2 85.2 — 85.2 72.3 — 72.3 Unituxin 42.8 1.1 43.9 48.3 4.8 53.1 44.8 10.5 55.3 42.2 7.8 50.0 Adcirca 9.6 — 9.6 23.6 — 23.6 14.6 — 14.6 8.1 — 8.1 Other — — — — — — — — — — — — Total revenues $ 354.3 $ 24.8 $ 379.1 $ 411.7 $ 34.8 $ 446.5 $ 412.1 $ 32.6 $ 444.7 $ 386.1 $ 29.1 $ 415.2 (1) Net product sales include both the drug product and the respective inhalation device. (2) Net product sales include sales of infusion devices including the Remunity Pump. Category: Earnings View source version on businesswire.com: Contacts Dewey Steadman at (202) 919-4097 Source: United Therapeutics Corporation View this news release online at:

Financial Statement

100 Deals associated with Dinutuximab

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KEGG	Wiki	ATC	Drug Bank
D10559	Dinutuximab	L01XC	DB09077

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Neuroblastoma	US	United Therapeutics Corp.	10 Mar 2015

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Ganglioneuroblastoma	Phase 3	US	National Cancer Institute	19 Apr 2024
Ganglioneuroblastoma	Phase 3	CA	National Cancer Institute	19 Apr 2024
Ganglioneuroblastoma	Phase 3	NZ	National Cancer Institute	19 Apr 2024
Small cell lung cancer recurrent	Phase 3	US	United Therapeutics Corp.	01 Jun 2017
Small cell lung cancer recurrent	Phase 3	AU	United Therapeutics Corp.	01 Jun 2017
Small cell lung cancer recurrent	Phase 3	BG	United Therapeutics Corp.	01 Jun 2017
Small cell lung cancer recurrent	Phase 3	CA	United Therapeutics Corp.	01 Jun 2017
Small cell lung cancer recurrent	Phase 3	FR	United Therapeutics Corp.	01 Jun 2017
Small cell lung cancer recurrent	Phase 3	GE	United Therapeutics Corp.	01 Jun 2017
Small cell lung cancer recurrent	Phase 3	HK	United Therapeutics Corp.	01 Jun 2017

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04385277 (ANBL19P1, CTgov)	Phase 2	Ganglioneuroblastoma	41	FDG-Positron Emission Tomography+Dinutuximab+Temozolomide+Isotretinoin+Sargramostim+Irinotecan	jiabtaejop(xgzfrrwkky) = vbihjwkbbn scytdyuvsj (njadcnvffo, iwxjhhshik - bhhytipiyw) View more	-	14 Aug 2024
ASCO2024 Manual	Not Applicable	High Risk Neuroblastoma	1,393	Dinutuximab	yeehnvhkfk(rvrexclfmm): RR = 0.41 (95% CI, 0.22 - 0.75), P-Value = 0.004 View more	Positive	24 May 2024
				Other therapies
ASCO2024	Not Applicable	High Risk Neuroblastoma anti-disialoganglioside (GD2)	2,214	Dinutuximab	gtgejyxsqp(jshnsqthcu) = iswqsyhcpl rymxnhtpcc (rhrnkdccso, 0.52 - 0.69) View more	Positive	24 May 2024
NCT03786783 (ANBL17P1, CTgov)	Phase 2	High Risk Neuroblastoma \| Ganglioneuroblastoma	42	External Beam Radiation Therapy+Etoposide+Carboplatin+Doxorubicin+Isotretinoin+Sargramostim+Topotecan+Dexrazoxane+Dinutuximab+Cyclophosphamide+Melphalan+Cisplatin+Vincristine+Thiotepa	zymljgijip(pveoqogufa) = umwwvfppur pgaznetlda (oghszwrgxw, rcftopmbkw - nmnlrazmfp) View more	-	14 Mar 2023
ASCO2022	Not Applicable	High Risk Neuroblastoma	143	Irinotecan/Temozolomide/Dinutuximab/Granulocyte-Macrophage Colony-Stimulating FactorIrinotecan/Temozolomide/Dinutuximab/Granulocyte-Macrophage Colony-Stimulating FactorIrinotecan/Temozolomide/Dinutuximab/Granulocyte-Macrophage Colony-Stimulating FactorIrinotecan/Temozolomide/Dinutuximab/Granulocyte-Macrophage Colony-Stimulating Factor	sbuohkodgh(jcxwltowve) = rscqoruoei uesxmgryzk (cbiwmaxujl )	Positive	02 Jun 2022
NCT03098030 (Pubmed)	Phase 3	Small Cell Lung Cancer Second line	471	Dinutuximab 16-17.5 mg/m2 + Irinotecan 350 mg/m2	vyuszowoef(jheekpjgpu) = vaypcwrozi kcjnijlxbz (ozjuzpiuhd ) View more	Negative	04 Mar 2022
				Irinotecan 350 mg/m2	vyuszowoef(jheekpjgpu) = eemvsldrjs kcjnijlxbz (ozjuzpiuhd ) View more
NCT02484443 \| NCT00066365 \| NCT02470091 (AOST1421, ASCO2021)	Phase 2	Osteosarcoma, Recurrent	-	Denosumab	toxydvunnw(ceoutbnnfx) = baffpvbfwm gtjzhryjcm (idemlumpmf, 10 - 42)	Negative	28 May 2021
				Dinutuximab	toxydvunnw(ceoutbnnfx) = lmnduhvnhg gtjzhryjcm (idemlumpmf, 17 - 45)
NCT02484443 (AOST1421, CTgov)	Phase 2	Secondary malignant neoplasm of lung \| Osteosarcoma, Recurrent \| Metastatic osteosarcoma	41	Pharmacological Study+Dinutuximab+Sargramostim	meysgclfll(odnfikgfgp) = jptrfhdiyj vynfyigpyx (qcxqvpcblp, pplhbmlvbo - nbwpzllwjk) View more	-	07 May 2021
NCT03098030 (CTgov)	Phase 2/3	Small cell lung cancer recurrent	483	Dinutuximab+irinotecan (Part 2: Dinutuximab + Irinotecan)	mszmmkyvwk(feboluhghg) = ebgtjfaiwl kzjnmgsspf (ydnwnniqyf, vkvjiltnig - wwgakzmmhk) View more	-	09 Dec 2020
				irinotecan (Part 2: Irinotecan)	mszmmkyvwk(feboluhghg) = ekjrbdezel kzjnmgsspf (ydnwnniqyf, qfupwierja - odprlbryol) View more
NCT03098030 (ASCO2020) Manual	Phase 2/3	Small Cell Lung Cancer Second line	471	Irinotecan+dinutuximab	bjrjohpvrf(jhhcdusjbh) = rslckbjvax kdvwbqceoa (fdhjymfduw, 3.5 - 10.9) View more	Negative	29 May 2020
				Irinotecan	bjrjohpvrf(jhhcdusjbh) = voxumzczdi kdvwbqceoa (fdhjymfduw, 3.6 - 13.1) View more

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Regulation

Understand key drug designations in just a few clicks with Synapse.

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Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

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Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis