On July 31, 2019 Novartis reported Kisqali (ribociclib) achieved statistically significant improvement in overall survival in the Phase III MONALEESA-3 clinical trial (Press release, Novartis, JUL 31, 2019, View Source [SID1234537927]). This is the second Phase III clinical trial in which Kisqali combination therapy met the key secondary endpoint of overall survival at the pre-planned interim analysis. MONALEESA-3 evaluated efficacy and safety of Kisqali plus fulvestrant in postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer in both the first-line and second-line settings.

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"We are thrilled that Kisqali combination therapy again has demonstrated improved overall survival for patients with HR+/HER2- advanced breast cancer – first in pre-menopausal and peri-menopausal women in MONALEESA-7, and now in post-menopausal women in MONALEESA-3," said Susanne Schaffert, PhD, President, Novartis Oncology. "We will continue to reimagine cancer to help patients live longer, and also improve quality of life as we work towards finding a cure for this incurable disease."

No new safety signals were observed; adverse events were consistent with previously reported Phase III trial results. Kisqali is approved for use in various indications in more than 75 countries around the world.

Novartis will present the full results at an upcoming medical congress and submit the data to global health authorities.

About Kisqali (ribociclib)
Kisqali (ribociclib) is the CDK4/6 inhibitor with the largest body of first-line clinical trial evidence demonstrating consistent and sustained efficacy compared to endocrine therapy alone[1]. Kisqali is the only CDK4/6 inhibitor to achieve statistically significant overall survival in two Phase III trials with two distinct patient populations[1]. Overall survival follow-up is ongoing for the Phase III MONALEESA-2 trial.

Novartis is continuing to reimagine cancer by investigating Kisqali in early breast cancer. The NATALEE study is a Phase III clinical trial of Kisqali with endocrine therapy in the adjuvant treatment of HR+/HER2- early breast cancer being conducted in collaboration with Translational Research In Oncology (TRIO)[1].

Kisqali is approved for use in more than 75 countries around the world, including the United States and European Union member states. Kisqali was initially approved by the US Food and Drug Administration (FDA) in March 2017 and by the European Commission (EC) in August 2017, as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor based on findings from the pivotal MONALEESA-2 trial. Kisqali in combination with an aromatase inhibitor was approved for the treatment of pre-, peri- or postmenopausal women as initial endocrine based therapy, and also indicated for use in combination with fulvestrant as both first- or second-line therapy in postmenopausal women by the FDA in July 2018 and by the EC in December 2018. Regulatory filings are underway with other health authorities worldwide[1].

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

About Novartis in Advanced Breast Cancer
Novartis tackles breast cancer with superior science, collaboration and a passion for transforming patient care. We’ve taken a bold approach to our research by including patient populations often neglected in clinical trials, identifying new pathways or mutations that may play a role in disease progression and developing therapies that not only maintain, but also improve, quality of life for patients. Our priority over the past 30 years and today is to deliver treatments proven to improve and extend lives for those diagnosed with advanced breast cancer.

Important Safety Information FROM THE Kisqali EU SmPC
Kisqali (ribociclib) is a prescription medicine approved in combination with an aromatase inhibitor as initial endocrine – based therapy in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer or fulvestrant as initial endocrine – based therapy or following disease progression on endocrine therapy in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. It is not known if Kisqali is safe and effective in children or adolescents. Kisqali can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death. Kisqali is not indicated for concomitant use with tamoxifen due to an increased risk of QT prolongation. Patients should tell their health care provider right away if they have a change in their heartbeat (a fast or irregular heartbeat), or if they feel dizzy or faint. Kisqali can cause serious liver problems. Patients should tell their health care provider right away if they get any of the following signs and symptoms of liver problems: yellowing of the skin or the whites of the eyes (jaundice), dark or brown (tea-colored) urine, feeling very tired, loss of appetite, pain on the upper right side of the stomach area (abdomen), and bleeding or bruising more easily than normal. Low white blood cell counts are very common when taking Kisqali and may result in infections that may be severe. Patients should tell their health care provider right away if they have signs and symptoms of low white blood cell counts or infections such as fever and chills. Before taking Kisqali, patients should tell their health care provider if they are pregnant, or plan to become pregnant as Kisqali can harm an unborn baby. Females who are able to become pregnant and who take Kisqali should use highly effective birth control during treatment and for at least 3 weeks after the last dose of Kisqali. Do not breastfeed during treatment with Kisqali and for at least 3 weeks after the last dose of Kisqali. Patients should tell their health care provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements since they may interact with Kisqali. Patients should avoid grapefruit or grapefruit juice while taking Kisqali. The most common side effects (incidence >=20%) include infections, white blood cell count decreases, headache, cough, nausea, tiredness, diarrhea, vomiting, constipation, hair loss and rash. The most common Grade 3/4 side effects (incidence >5%) were infections, low neutrophils, low leukocytes, low red blood cells, abnormal liver function tests, low lymphocytes, low phosphate levels and vomiting. Abnormalities were observed in hematology and clinical chemistry laboratory tests.

On July 31, 2019 Takeda Pharmaceutical Company Limited (TOKYO:4502)(NYSE:TAK) (Press release, Takeda, JUL 31, 2019, View Source [SID1234537913]):

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Underlying Revenue declined -0.8% vs FY2018 Q1 pro-forma revenue1

Takeda’s 14 global brands, with an aggregate revenue of 270.2 billion yen posted strong year-over-year growth of +22%. This growth mostly offset the negative impact from intensified competition, phasing, and generic erosion.
Takeda’s 5 key business areas represent ~78% of revenues.
GI grew +8% spearheaded by ENTYVIO continuing to gain market share.
Plasma Derived Therapy (PDT) Immunology grew +2% driven by Albumin growth, with Immunoglobulin (IG) sales impacted by phasing of Intravenous Immunoglobulin (IVIG) shipments.

Rare Diseases declined -10% with rare hematology impacted by competition and price pressure, and strong uptake of TAKHZYRO not fully offsetting the decline of other Hereditary Angioedema (HAE) products due to the switch to TAKHZYRO and stocking in FY2018 Q1.

Oncology grew +8% driven by expansion of NINLARO.

Neuroscience grew +10% driven by the U.S. business under a new commercial structure.

Underlying Core Operating Profit Margin 32.4% for Q1

Reported Operating Profit declined 90.0% to 9.9 billion yen, largely impacted by one-time integration costs as well as non-cash purchase accounting expenses including unwinding of inventory step-up, and increased amortization of intangibles and impairment.
Underlying Core Operating Profit Margin for the current period was 32.4% reflecting synergy savings and continued OPEX discipline.
Achieved several important pipeline milestones in Q1

Currently 19 New Molecular Entity assets in Phase 2 & 3.
Advances in Cell and Gene Therapy platforms where CAR-T Cell Therapy from T-CiRA moves towards clinic and the integration of Adeno-Associated Virus-based (AAV-based) process development and manufacturing center in Austria.
ENTYVIO subcutaneous formulation achieved primary endpoint as maintenance therapy in Crohn’s disease.
Orexin 2 receptor agonist TAK-925 received Sakigake Designation in Japan for treatment of narcolepsy.
Disposing non-core assets to generate cash and focus the business

Net debt / adjusted EBITDA reduced from 4.7x at end of FY2018 to 4.4x as of June 2019, which does not include the $3.4 billion upfront cash payment received July 1, 2019 for the sale of XIIDRA to Novartis.
Sale of TACHOSIL remains on track to close in second half of calendar year.
Negotiations ongoing for further potential divestments.
Costa Saroukos, Chief Financial Officer, commented:

"Takeda had a very strong start to the year, delivering on our strategic priorities while successfully executing the integration of Shire. The combination of solid performance across our 14 global brands, continued OPEX discipline, and realization of cost synergies resulted in strong margins and cash flow. We are also making steady progress against our divestiture plan, with the completion of the XIIDRA sale on July 1st.
For the full year, Takeda has revised management guidance upward to reflect updated VELCADE assumptions and divestitures, and now anticipates delivering an Underlying Core Operating Profit margin in the mid-to-high twenties.
Takeda is relentlessly executing towards our cost synergy, de-leveraging, and margin targets. We remain on track to achieve our previously raised cost synergy target of $2 billion by the end of FY 2021, we are committed to achieving our 2x net debt / adjusted EBITDA target over the next three to five years, and our strong start to fiscal 2019 gives us great confidence towards realizing top-tier margins in the medium-term."

Underlying Growth compares two periods (quarters or years) of financial results under a common basis and is used by management to assess the business. These financial results are calculated on a constant currency basis and excluding the impact of divestitures and other amounts that are unusual, non-recurring items or unrelated to our ongoing operations.
Growth versus FY2018 Q1 pro-forma revenue. Pro forma adjustments to reflect amortization of intangible assets as if the acquisition of Shire had occurred at the beginning of FY2018, while removing non-recurring costs related to the acquisition such as transaction costs. The adjustments also include removal of impacts related to Shire’s oncology business which was divested in August 2018.
Core Operating Profit represents net profit adjusted to exclude income tax expenses, our share of profit or loss of investments accounted for using the equity method, finance expenses and income, other operating expenses and income, amortization and impairment losses on intangible assets associated with products and other items that management believes are unrelated to our core operations, such as purchase accounting effects and transaction related costs
Attributable to the owners of the company.
Not Meaningful
FY2019 Management Guidance: Upward revision to reflect changes to assumptions

Takeda no longer assumes any additional U.S. competitor for VELCADE within FY2019
Reflects divestitures of XIIDRA (closed July 1, 2019) and TACHOSIL (expected close CY2019 H2)

vi. Constant Exchange Rate growth (applying FY2018 full year average foreign exchange rate). Compared to baseline of 3,300 billion JPY (rounded pro-forma April 2018 – March 2019 combined revenue of Legacy Takeda and Legacy Shire, converted at April 2018 – March 2019 average exchange rate of 111 JPY/USD; also adjusted to remove the revenue from divested assets such as Techpool, Multilab, and TACHOSIL from Legacy Takeda, and the oncology portfolio and XIIDRA from Legacy Shire)

FY2019 Reported Forecast: Increasing Earnings forecasts with Reported Revenue forecast unchanged

For more details on Takeda’s FY2019 1st quarter results and other financial information, please visit View Source

On July 30, 2020 Oncoceutics, Inc. reported that a series of presentations at the 2019 DIPG/DMG Symposium to be held August 2-3 in Sydney, Australia, will highlight ONC201 as a promising treatment for specific types of lethal brain cancer (Press release, Oncoceutics, JUL 30, 2019, View Source [SID1234558335]). These presentations are part of a session describing progress in new drug development for diffuse midline gliomas (DMG), which includes diffuse intrinsic pontine glioma (DIPG).

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The first of the ONC201-related talks will describe the clinical experience with ONC201, the first small molecule DRD2 antagonist for oncology, in pediatric patients with gliomas containing a specific mutation, called H3 K27M, that has a high prevalence in DMGs and DIPGs. Sharon Gardner, MD, New York University, who is the principal investigator of the clinical trial, will present the clinical data. The next talk will feature William Hoos, CCO of XCures, who will present on the topic of innovative trial designs, which will highlight the partnership between Oncoceutics and XCures that enables efficient clinical research and data collection in ultra-rare diseases. Wolfgang Oster, MD, PhD, CEO and Chairman of Oncoceutics, will provide an industry perspective on drug development for DMGs as part of the same session on August 3rd.

These presentations report results from systematic clinical studies with ONC201 combined with a real-life experience gathered in an Expanded Access Program (EAP), when patients are not able to enroll on a clinical protocol but fulfill a narrowly defined set of characteristics that mimic the ones in clinical studies. Ongoing and planned clinical programs with ONC201 for DIPG and DMG were presented on June 20, 2019 at the Pediatric Subcommittee of the FDA’s Oncology Drugs Advisory Committee. A webcast recording of this event can be viewed at the following link (required Adobe Connect): View Source

A team of Oncoceutics members will be present at the conference in Sydney. If you have any questions please contact us at [email protected].

On July 30, 2019 Peptomyc reported that amounting to 2.2 million euros over 2 years, this latest funding from the EU Horizon 2020 Research and Innovation programme is a huge step toward clinical trials, due to start in 2020 (Press release, Peptomyc, JUL 30, 2019, View Source [SID1234555337]). The grant will help with regulatory safety studies and activities of Peptomyc’s first product, OMO-103, including its clinical batch production, and the design, recruitment of patients and performance of Phase I/IIa clinical trials.

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Peptomyc and the laboratory of Dr. Soucek previously received an ERC Consolidator Grant and 2 separate Proof-of-Concept grants from the Horizon 2020 programme, and also an SME Instrument Phase I. These have all contributed significantly to bringing OMO-103 to its current level of development.

On July 30, 2019 SpringWorks Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported that the European Commission has granted Orphan Drug Designation for mirdametinib (formerly PD-0325901), an oral, small molecule inhibitor of MEK1 and MEK2, for the treatment of neurofibromatosis type 1 (NF1) (Press release, SpringWorks Therapeutics, JUL 30, 2019, View Source [SID1234538849]).

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NF1 is a rare genetic disorder characterized by mutations in the MAPK pathway. Throughout their lifetime, up to half of NF1 patients progress to develop plexiform neurofibromas, which are peripheral nerve sheath tumors that cause significant pain, disfigurement and morbidity. NF1-associated plexiform neurofibromas (NF1-PN) are most often diagnosed in the first two decades of life and are characterized by aggressive tumor growth, which is typically more rapid during childhood.1-3 There are currently no therapies approved for the treatment of NF1-PN.

"This orphan designation in the European Union is another important recognition of the significant need for an effective treatment for patients with NF1, and follows the orphan drug and fast-track designations already granted for mirdametinib in the U.S. by the FDA," said Saqib Islam, Chief Executive Officer of SpringWorks. "We expect to initiate our Phase 2b trial of mirdametinib in children and adults with NF1-PN this quarter and look forward to working closely with regulatory authorities throughout our development program."

The European Commission grants orphan medicinal status for products intended for the treatment, prevention or diagnosis of life-threatening or very serious conditions that affect no more than 5 in 10,000 people in the European Union, and where the product represents a significant benefit over existing treatments. Orphan designation provides companies with certain benefits and incentives in the EU, including a 10-year period of market exclusivity after product approval, reduced regulatory fees and protocol assistance.4

Mirdametinib previously received Orphan Drug Designation from the FDA for the treatment of neurofibromatosis type 1 and Fast Track Designation from the FDA for the treatment of patients ≥ 2 years of age with neurofibromatosis type 1-associated inoperable plexiform neurofibromas that are progressing or causing significant morbidity. SpringWorks expects to initiate the ReNeu trial, a Phase 2b open-label, single-arm trial with mirdametinib that will enroll both pediatric and adult NF1-PN patients, in the third quarter of 2019.

About Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is a rare genetic disorder that arises from mutations in the NF1 gene, which encodes for neurofibromin, a key suppressor of the MAPK pathway. NF1 is the most common form of neurofibromatosis, with an estimated global birth incidence of approximately 1 in 3,000 individuals.2,3 The clinical course of NF1 is heterogeneous and manifests in a variety of symptoms across numerous organ systems, including abnormal pigmentation, skeletal deformities, tumor growth and neurological complications, such as cognitive impairment. Patients with NF1 have an eight to 15-year mean reduction in their life expectancy compared to the general population.5 NF1 patients have an approximately 30% to 50% lifetime risk of developing plexiform neurofibromas, or PN, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment; in rare cases, NF1-PN may be fatal.2,3 NF1-PN are most often diagnosed in the first two decades of life. These tumors are characterized by aggressive growth, which is typically more rapid during childhood.1,2,5 The only definitive treatment for NF1-PN is surgical removal of the tumors, however, because NF1-PN arise from nerve cells and grow in an infiltrative pattern, it is challenging to successfully resect tumors without severe comorbidities, such as permanent nerve damage and disfigurement. 6 There are no therapies currently approved for the treatment of NF1-PN.

About Mirdametinib

Mirdametinib is an oral, small molecule inhibitor of MEK1 and MEK2. MEK proteins occupy a pivotal position in the MAPK pathway, a key signaling network that regulates cell growth and survival, and that plays a central role in multiple oncology and rare disease indications.

Mirdametinib has been evaluated in several Phase 1 and Phase 2 clinical trials, with over 200 subjects having been exposed to treatment. A Phase 2 trial was conducted by the Neurofibromatosis Clinical Trial Consortium and evaluated mirdametinib in 19 adolescent and adult patients with inoperable and symptomatic or growing plexiform neurofibromas. Patients received an oral dose of 2 mg/m2 BID with a maximum dose of 4 mg BID on a four-week cycle of three weeks-on, one week-off. Eight patients (42%) achieved an objective response by cycle 12, prospectively defined as volumetric reduction in their target PN of at least 20 percent. Mirdametinib was generally well-tolerated in this trial. The most commonly reported treatment-emergent grade 2 or higher AEs were acneiform rash in 53% (10/19), fatigue in 26% (5/19) and nausea in 21% (4/19) of patients.

In addition to the Phase 2b monotherapy trial in NF1-associated PN, and given the critical role that the MAPK pathway plays in the growth and proliferation of a large number of tumor types, SpringWorks is also pursuing mirdametinib in combination with other rational anticancer agents across a range of solid tumors.