On March 31, 2021 Zai Lab (NASDAQ: ZLAB; HKEX: 9688), an innovative commercial-stage biopharmaceutical company, and Deciphera Pharmaceuticals (NASDAQ: DCPH), a commercial-stage biopharmaceutical company developing innovative medicines to improve the lives of people with cancer, reported that the China National Medical Products Administration (NMPA) has approved its New Drug Application (NDA) for QINLOCK (ripretinib) for the treatment of adult patients with advanced gastrointestinal stromal tumors (GIST) who have received prior treatment with three or more kinase inhibitors, including imatinib (Press release, Deciphera Pharmaceuticals, MAR 31, 2021, View Source [SID1234577407]). QINLOCK targets the broad spectrum of KIT and PDGFRα mutations known to drive GIST.

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"Treatment of GIST remains an important unmet medical need in China," said Dr. Samantha Du, Founder, Chairperson, and Chief Executive Officer of Zai Lab. "Approximately 30,000 GIST patients are newly diagnosed each year in China, twice as many as in the U.S. and Europe combined. NMPA’s approval of QINLOCK establishes a new standard of care for treating patients with fourth-line GIST in China. We appreciate the NMPA’s rapid and thorough assessment of QINLOCK. We look forward to working closely with our partner, Deciphera, to introduce this new treatment option to benefit many more patients who are suffering from advanced GIST in Greater China."

"We congratulate Zai on gaining this important approval," said Steve Hoerter, President and Chief Executive Officer of Deciphera. "QINLOCK is a new standard of care for patients with fourth-line GIST, and we’re excited to work with our partner Zai as they deliver this innovative medicine to patients in China."

"The approval of QINLOCK in China is a significant milestone for the GIST community," said Dr. Shukui Qin, Chief Physician of Cancer Center, Nanjing Jinling Hospital, Senior Vice President of the Chinese Society of Clinical Oncology. "Many GIST patients, who initially responded to traditional tyrosine kinase inhibitors, ultimately developed tumor progression due to secondary mutations. QINLOCK may potentially alter the treatment landscape for patients in China with GIST."

"Based on the pivotal Phase 3 INVICTUS study, QINLOCK demonstrated compelling clinical benefit in progression-free and overall survival, and was shown to have a favorable safety profile in treating advanced GIST patients," said Dr. Lin Shen, Vice President of Clinical Oncology at Beijing Cancer Hospital. "We look forward to making this innovative therapy available to patients as soon as possible."

Deciphera and Zai Lab are also exploring the use of QINLOCK to treat patients with second-line GIST. Deciphera has completed target enrollment in the Phase 3 INTRIGUE study of QINLOCK in patients with second-line GIST, with top-line results anticipated in the second half of 2021.

About QINLOCK (ripretinib)

QINLOCK is a switch-control tyrosine kinase inhibitor that was engineered to broadly inhibit KIT and PDGFRα mutated kinases by using a dual mechanism of action that regulates the kinase switch pocket and activation loop. QINLOCK inhibits primary and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18 involved in GIST, as well as the primary exon 17 D816V mutation. QINLOCK also inhibits primary PDGFRα mutations in exons 12, 14, and 18, including the exon 18 D842V mutation, involved in a subset of GIST.

In March 2021, the NMPA approved QINLOCK for the treatment of adult patients with advanced GIST who have received prior treatment with three or more kinase inhibitors, including imatinib. In March 2021, the Hong Kong Department of Health approved QINLOCK in Hong Kong for the treatment of adult patients with advanced GIST who have received prior treatment with imatinib, sunitinib, and regorafenib. In May 2020, the U.S. FDA approved QINLOCK for the treatment of adult patients with advanced GIST who received prior treatment with three or more kinase inhibitors, including imatinib. It is also approved by Health Canada for the treatment of adult patients with advanced GIST who have received prior treatment with imatinib, sunitinib, and regorafenib and by the Australian Therapeutic Goods Administration for the treatment of adult patients with advanced GIST who have received prior treatment with three or more kinase inhibitors, including imatinib.

Zai Lab has an exclusive license agreement with Deciphera for the development and commercialization of ripretinib in Greater China (mainland China, Hong Kong, Macau and Taiwan).

About the INVICTUS Phase 3 Study

INVICTUS is a Phase 3 randomized, double-blind, placebo-controlled, international, multicenter clinical study evaluating the safety, tolerability, and efficacy of QINLOCK compared to placebo in patients with advanced GIST whose previous therapies have included imatinib, sunitinib, and regorafenib. Patients were randomized 2:1 to either 150 mg of QINLOCK or placebo once daily. The primary efficacy endpoint is progression-free survival (PFS) as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST). The median PFS in the study was 6.3 months compared to 1.0 month in the placebo arm and significantly reduced the risk of disease progression or death by 85% (hazard ratio of 0.15, p<0.0001). Secondary endpoints as determined by independent radiologic review using modified RECIST include Objective Response Rate (ORR) and Overall Survival (OS). QINLOCK demonstrated an ORR of 9.4% compared with 0% for placebo (p =0.0504). QINLOCK also demonstrated a median OS of 15.1 months compared to 6.6 months in the placebo arm and reduced the risk of death by 64% (hazard ratio of 0.36).

Important Safety Information

There are no contraindications for QINLOCK. The most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome (PPES), and vomiting. The most common Grade 3 or 4 laboratory abnormalities (≥4%) were increased lipase and decreased phosphate.

On March 31, 2021 CTI BioPharma Corp. (Nasdaq: CTIC) reported that it has completed a rolling New Drug Application ("NDA") submission to the U.S. Food and Drug Administration ("FDA") seeking approval of pacritinib as a treatment for myelofibrosis patients with severe thrombocytopenia (platelet counts less than 50 x 109/L) (Press release, CTI BioPharma, MAR 31, 2021, View Source [SID1234577406]). CTI had previously announced the results of a pre-NDA meeting with FDA where agreement was reached on an NDA submission package based upon available data from the completed Phase 3 PERSIST-1 and PERSIST-2 trials and the Phase 2 PAC203 trials.

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"The completion of the pacritinib NDA submission is the result of many years of clinical research and a collaborative and constructive dialogue with the FDA on how pacritinib could address the unmet medical need of myelofibrosis ("MF") patients with severe thrombocytopenia. MF patients with severe thrombocytopenia experience poor treatment outcomes, primarily due to their severely cytopenic disease and the significant limitations of approved therapies," said Adam R. Craig, M.D., Ph.D., President and Chief Executive Officer of CTI BioPharma. "CTI has initiated pre-commercialization activities and has completed the hiring of a commercial leadership team. Assuming a successful priority review of the NDA, we are preparing for a commercial launch of pacritinib before the end of 2021. We look forward to providing updates on the NDA and our commercialization plans over the coming months."

About Myelofibrosis and Severe Thrombocytopenia
Myelofibrosis is a type of bone marrow cancer that results in formation of fibrous scar tissue and can lead to severe cytopenias, including thrombocytopenia and anemia, as well as weakness, fatigue and an enlarged spleen and liver. Patients with severe thrombocytopenia are estimated to make up more than one-third of patients treated for myelofibrosis, or approximately 17,000 people in the United States and Europe. Severe thrombocytopenia, defined as blood platelet counts of less than 50,000 per microliter, has been shown to result in overall survival rates of just 15 months. Thrombocytopenia in patients with myelofibrosis is associated with the underlying disease but has also been shown to correlate with treatment with ruxolitinib, which can lead to dose reductions, and as a result, may potentially reduce clinical benefit. Survival in patients who have discontinued ruxolitinib therapy is further compromised, with an average overall survival of seven to 14 months. Myelofibrosis patients with severe thrombocytopenia have limited treatment options, creating a significant area of unmet medical need.

About Pacritinib
Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, IRAK1, and CSF1R. The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia, and lymphoma. In addition to myelofibrosis, the kinase profile of pacritinib suggests its potential therapeutic utility in conditions such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and chronic lymphocytic leukemia (CLL), due to its inhibition of c-fms, IRAK1, JAK2 and FLT3.

On March 31, 2021 Complix, a biopharmaceutical company developing a pipeline of transformative Alphabody therapeutics reported the publication in Science Advances of the results from a joint, multidisciplinary study with Belgian life sciences research Institute VIB and Ghent University (Press release, Complix, MAR 31, 2021, View Source;utm_medium=rss&utm_campaign=complix-and-vib-publish-pioneering-study-on-cell-penetrating-alphabodies-in-science-advances [SID1234577405]). The proof-of-concept study demonstrates the potential of Cell-Penetrating Alphabodies (CPABs) to efficiently penetrate the cancer cell membrane, disrupt an intracellular protein-protein interface, and cause an anti-tumor effect upon in vivo administration in relevant xenograft models.

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The article by Pannecoucke et al. can be accessed by clicking here.

CPABs are a revolutionary class of small proteins that have been designed to overcome the limitations of conventional antibodies and small molecules through combining the specific potency of biologics with the cell-penetrating capacity and stability of small molecules. Data available show that CPABs have the potential to address a wide range of disease targets, particularly intracellular targets, that are difficult for current therapies to reach.

The study, published in Science Advances, demonstrates that CPABs can be designed to efficiently penetrate the cell membrane, disrupt an intracellular protein-protein interface, and carry an albumin-binding moiety to extend their serum half-life to therapeutically relevant levels. The unique combination of these three features in a single protein scaffold is without precedent. In this publication a CPAB was engineered against MCL-1, an intracellular protein target in cancer.

The findings from this study provide strong proof of concept for the use of CPABs against intracellular disease mediators, which, to date, have remained in the realm of small-molecule therapeutics.

Dr. Ignace Lasters, CTO of Complix, commented:
"We are pleased to see the publication of this important study, which is a clear validation of our platform and highlights the potential of CPABs to directly address intracellular drug targets in oncology. Reaching the intracellular space has been a critical limiting factor in broadening the therapeutic potential of current biologicals such as monoclonal antibodies. This proof-of-concept study clearly demonstrates the potential of CPABs as a transformative, "membrane crossing" technology to address a variety of cutting-edge and challenging intracellular disease targets. This holds the promise for the creation of an entirely novel class of therapeutics with applications in oncology and beyond."

Prof. Savvas Savvides, Group leader at VIB Center for Inflammation Research, and Professor of Structural Biology at Ghent University, said:
"Our study clearly extends the currently charted protein-based drug-targeting landscape by targeting the well-known intracellular drug target MCL–1, a protein upregulated in multiple tumor types and correlated with therapy resistance. It is very exciting and rewarding to see how our longstanding collaboration with Complix has matured to provide the essential knowledge needed to tackle such a major and important challenge in the design of novel therapeutics."

Scientific publication
Erwin Pannecoucke, Maaike Van Trimpont, Johan Desmet, Tim Pieters, Lindy Reunes, Lisa Demoen, Marnik Vuylsteke, Stefan Loverix, Karen Vandenbroucke, Philippe Alard, Paula Henderikx, Sabrina Deroo, Franky Baatz, Eric Lorent, Sophie Thiolloy, Klaartje Somers, Yvonne McGrath, Pieter Van Vlierberghe, Ignace Lasters, Savvas N. Savvides. Cell-penetrating Alphabody protein scaffolds for intracellular drug targeting. Science Advances, 26 March 2021: Vol. 7, no. 13.

On March 31, 2021 Takeda Pharmaceutical Company Limited (TOKYO:4502) (NYSE:TAK) ("Takeda") reported the completion of its previously-announced sale of Takeda Consumer Healthcare Company Limited ("TCHC") to Oscar A-Co KK, a company controlled by funds managed by The Blackstone Group Inc. and its affiliates (collectively "Blackstone") for a total value of JPY 242.0 billion1 (Press release, Takeda, MAR 31, 2021, View Source [SID1234577384]). This divestment agreement was first announced in August 2020.

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Following the transfer of shares, TCHC will be excluded from the scope of consolidation of Takeda2, and operates as Alinamin Pharmaceutical Co., Ltd ("Alinamin Pharmaceuticals").

The divested portfolio included a variety of over-the-counter ("OTC") medicines and health products that generated total revenues of over JPY 60.0 billion in fiscal year 2019. TCHC’s strong regional brands included Alinamin, its top selling product and Japan’s first vitamin B1 preparation, and Benza, a cold remedy. Takeda is confident that under Blackstone, Alinamin Pharmaceuticals will be well-positioned to continue growing and developing its product offerings in the years to come to address the evolving needs of consumers.

Takeda intends to use the proceeds from the sale to reduce its debt and accelerate deleveraging towards its target of 2x net debt/adjusted EBITDA within FY2021 – FY2023.

Takeda has sustained momentum in its divestiture strategy and has exceeded its $10 billion non-core asset divestiture target. Takeda has announced 12 deals since January 2019, for a total aggregate value of up to approximately $12.9 billion.

The sales price is currently anticipated to be approximately JPY 230.0 billion, subject to certain adjustments, including net debt and working capital of TCHC and Takeda Healthcare Products Company Limited as of March 31, 2021. With the completion of the transfer of shares, a pre-tax gain of approximately JPY 140.0 billion on the sale of shares of a subsidiary will be recognized, and Takeda anticipates Reported Net Profit attributable to owners of the Company to increase by approximately the same amount in the fiscal year ending March 31, 2021 (FY2020). Since the gain on the sale of shares of the subsidiary relates to the divestiture of a non-core business, there will be no impact on Core Operating Profit or Core Net Profit.

1 Enterprise value. Actual sales price will be determined after adjustment for items including net debt and working capital of TCHC and Takeda Healthcare Products Company Limited ("THP").
2 As a result of the share transfer, a wholly owned subsidiary of TCHC, THP, will also be excluded from the scope of consolidation of Takeda.

On March 31, 2021 Ipsen (Euronext: IPN; ADR: IPSEY) reported that the European Commission (EC) has approved Cabometyx (cabozantinib) in combination with Bristol Myers Squibb’s Opdivo (nivolumab) for the first-line treatment of advanced renal cell carcinoma (aRCC) (Press release, Ipsen, MAR 31, 2021, View Source [SID1234577383]). This decision marks the first approval for Cabometyx in combination with another therapy in Europe and the third indication of Cabometyx in renal cell carcinoma (RCC).

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"Today’s EC approval for the use of Cabometyx in combination with Opdivo provides an important new first-line treatment option for patients living with advanced renal cell carcinoma," said Howard Mayer, Executive Vice President and Head of Research and Development, Ipsen. "At Ipsen, we’re proud that this, now approved, treatment option not only addresses key efficacy benefits, but also the need to maintain quality of life for patients. We look forward to collaborating with a broad range of European stakeholders to bring this unique combination to eligible patients living with advanced renal cell carcinoma."

The EC approval is based on results from the pivotal Phase III CheckMate -9ER trial, presented during a Presidential Symposium at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020 and published in the New England Journal of Medicine (NEJM) on 3 March 2021. In the trial, Cabometyx in combination with Opdivo demonstrated significant improvements across all efficacy endpoints. In patients receiving the combination, median progression-free survival (PFS), the trial’s primary endpoint, was doubled compared to those receiving sunitinib alone: 16.6 months vs. 8.3 months respectively (HR: 0.51; 95% CI: 0.41–0.64; p<0.0001).1 Overall survival (OS) also demonstrated statistically significant improvements, reducing the risk of death by 40% versus sunitinib (HR: 0.60 [98.89% CI: 0.40-0.89]; p=0.001; median OS not reached in either arm).1 In addition, Cabometyx in combination with Opdivo demonstrated a superior objective response rate (ORR), with twice as many patients responding compared to sunitinib (55.7% vs. 27.1%; p<0.0001) and 8.0% vs. 4.6% achieved a complete response respectively.1 Key efficacy results were consistent across the pre-specified International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk and PD-L1 subgroups.1 The combination was well tolerated and reflected the known safety profiles of the immunotherapy and tyrosine kinase inhibitor components in first-line aRCC.1

Additional data from the CheckMate -9ER trial were also presented in February at the recent American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Genitourinary Cancers Symposium (ASCO GU). These data highlighted sustained superior efficacy of Cabometyx in combination with Opdivo versus sunitinib for the first-line treatment of aRCC with a median follow-up of 23.5 months, as well as data suggesting significantly improved health-related quality of life (HRQoL) outcomes for the combination versus sunitinib.2,3 These HRQoL data, also included as part of the recently published NEJM publication, demonstrated that the combination was associated with a lower treatment burden, a decline in the risk of confirmed deterioration in HRQoL and a reduction of disease-related symptoms compared to sunitinib.1,3

"The combination of nivolumab and cabozantinib pairs two proven agents for advanced renal cell carcinoma that together have shown superior efficacy across key endpoints and subgroups of patients compared to sunitinib in the CheckMate -9ER trial. Additionally, the combination’s safety profile was manageable with known protocols, leading to a low rate of treatment-related discontinuations," said Marc- Oliver Grimm, M.D., Professor of Medicine and Urology Department Head, Jena University Hospital. "With today’s approval, clinicians in the EU will be able to offer patients with advanced renal cell carcinoma an additional combination therapy that may help them achieve early control of their disease and improve survival outcomes."

This approval allows for the marketing of Cabometyx in combination with Opdivo in this indication in all 27 member states of the European Union, Norway, Liechtenstein and Iceland. The U.S. Food and Drug administration approved Cabometyx for patients with aRCC as a first-line treatment in combination with Opdivo in January 2021.

Ipsen thanks the patients and investigators involved in the CheckMate -9ER clinical trial.

About renal cell carcinoma
There are over 400,000 new cases of kidney cancer diagnosed worldwide each year.4 Of these, renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for approximately 90% of cases.5,6 It is twice as common in men, and male patients account for over two thirds of deaths.4 If detected in the early stages, the five-year survival rate is high, but for patients with advanced or late- stage metastatic RCC the survival rate is much lower, around 12%, with no identified cure for this disease.7,8

About the CheckMate -9ER trial
CheckMate -9ER is an open-label, randomized, multi-national Phase III trial evaluating patients with previously untreated advanced or metastatic RCC. A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 ≥1%) were randomized to Cabometyx plus Opdivo (n= 323) versus sunitinib (n= 328). The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS) and objective response rate (ORR). The primary efficacy analysis is comparing the doublet combination versus sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.

About Cabometyx (cabozantinib)
Cabometyx is currently approved in 57 countries, including in the European Union, the U.K., Norway, Iceland, Liechtenstein, Australia, New Zealand, Switzerland, South Korea, Canada, Brazil, Taiwan, Hong- Kong, Singapore, Macau, Jordan, Lebanon, Russian Federation, Ukraine, Turkey, United Arab Emirates, Saudi Arabia, Serbia, Israel, Mexico, Chile, Peru, Panama, Guatemala, Dominican Republic, Ecuador and Thailand for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy; in the European Union, the U.K., Liechtenstein, Norway, Iceland, Canada, Australia, Brazil, Taiwan, Hong Kong, Singapore, Lebanon, Jordan, Russian Federation, Ukraine, Turkey, United Arab Emirates, Saudi Arabia, Israel, Mexico, Chile, Peru, Panama, Guatemala, Dominican Republic, Ecuador and Thailand for previously untreated intermediate- or poor-risk advanced RCC; and in the European Union, the U.K., Liechtenstein, Norway, Iceland, Canada, Australia, Switzerland, Saudi Arabia, Serbia, Israel, Taiwan, Hong Kong, South Korea, Singapore, Jordan, Russian Federation, Ukraine, Turkey, Lebanon, United Arab Emirates, Peru, Panama, Guatemala, Chile, Dominican Republic, Ecuador and Thailand for HCC in adults who have previously been treated with sorafenib.

The detailed recommendations for the use of Cabometyx are described in the Summary of Product Characteristics (SmPC) and in the U.S. Prescribing Information (PI).

Cabometyx is marketed by Exelixis, Inc. in the United States and by Takeda Pharmaceutical Company Limited in Japan. Ipsen has exclusive rights for the commercialization of Cabometyx outside of the U.S. and Japan. Cabometyx is a registered trademark of Exelixis, Inc.