On March 19, 2021 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Merck & Co., Inc., Kenilworth, N.J., U.S.A. (known as MSD outside the United States and Canada) reported the first presentation of investigational data from the pivotal Phase 3 Study 309/KEYNOTE-775 trial in an oral plenary session (Plenary Session #10191) at the virtual Society of Gynecologic Oncology (SGO) 2021 Annual Meeting on Women’s Cancer (Press release, Eisai, MAR 19, 2021, View Source [SID1234576899]). The trial evaluated the combination of LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, plus KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A., for the treatment of certain patients with advanced, metastatic or recurrent endometrial cancer following one prior platinum-based regimen in any setting.

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The study met the dual primary endpoints of progression-free survival (PFS), as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, overall survival (OS), as well as the secondary efficacy endpoint of objective response rate (ORR), as assessed by BICR per RECIST v1.1, in the all-comer population (mismatch repair proficient [pMMR] and mismatch repair deficient [dMMR]) and in the pMMR subgroup. Median follow-up was 11.4 months for both the all-comer population and pMMR subgroup. A statistically significant and clinically meaningful improvement in PFS was seen in the all-comer population, in which LENVIMA plus KEYTRUDA (n=411) reduced the risk of disease progression or death by 44% (HR=0.56 [95% CI: 0.47-0.66]; p<0.0001), with a median PFS of 7.2 months (95% CI: 5.7-7.6; number of events=281) versus 3.8 months (95% CI: 3.6-4.2; number of events=286) for patients who received chemotherapy (treatment of physician’s choice [TPC] of doxorubicin or paclitaxel; n=416). Additionally, a statistically significant and clinically meaningful improvement in OS was seen in the all-comer population, in which LENVIMA plus KEYTRUDA reduced the risk of death by 38% (HR=0.62 [95% CI: 0.51-0.75]; p<0.0001), with a median OS of 18.3 months (95% CI: 15.2-20.5; number of events=188) versus 11.4 months (95% CI: 10.5-12.9; number of events=245) for patients who received TPC. The safety profile of LENVIMA plus KEYTRUDA was generally consistent with the established safety profiles of the individual monotherapies.

"Patients diagnosed with endometrial cancer, the most common type of gynecologic cancer in the U.S., face low survival rates when diagnosed at an advanced stage or at recurrence, especially once the disease progresses after prior platinum-based therapy and is not amenable to curative surgery or radiation," said Dr. Vicky Makker, Principal Investigator and Medical Oncologist, Memorial Sloan Kettering Cancer Center. "With a 38% reduction in risk of death regardless of mismatch repair status, LENVIMA plus KEYTRUDA significantly improved overall survival compared with chemotherapy in the all-comer group of patients with advanced, metastatic or recurrent endometrial carcinoma, which is very encouraging, as this arm included an investigational patient population for which more data have been sought after by the gynecologic oncology community."

In the all-comer population, the secondary efficacy endpoint of ORR was 31.9% (95% CI: 27.4-36.6), with a complete response (CR) rate of 6.6% and a partial response (PR) rate of 25.3%, for patients who received LENVIMA plus KEYTRUDA versus 14.7% (95% CI: 11.4-18.4), with a CR rate of 2.6% and a PR rate of 12.0% for patients who received TPC (ORR difference versus TPC: 17.2 percentage points; p<0.0001). For patients who responded, the median duration of response (DOR) was 14.4 months (range: 1.6-23.7) for patients who received LENVIMA plus KEYTRUDA versus 5.7 months (range: 0.0-24.2) for patients who received TPC.

"In this confirmatory Phase 3 study, KEYTRUDA plus LENVIMA demonstrated statistically significant improvements in progression-free survival, overall survival and objective response rate versus chemotherapy," said Dr. Gregory Lubiniecki, Vice President, Oncology Clinical Research, Merck & Co., Inc., Kenilworth, N.J., U.S.A. Research Laboratories. "We are encouraged by these results that reaffirm the companies’ commitment to explore the potential of the combination to help more patients with difficult-to-treat types of cancer."

"The positive results seen in Study 309/KEYNOTE-775 help confirm the currently approved use of the LENVIMA plus KEYTRUDA combination in certain patients with advanced endometrial carcinoma," said Dr. Takashi Owa, Chief Medicine Creation Officer and Chief Discovery Officer, Oncology Business Group at Eisai. "As this stage of disease has been notoriously difficult to treat, the companies remain committed to addressing the unmet need of advanced endometrial carcinoma. We are grateful to the patients and health care providers whose participation and persistence amid a global pandemic have made this milestone possible."

Results were similar across the all-comer population and the pMMR subgroup. In the pMMR subgroup, LENVIMA plus KEYTRUDA reduced the risk of disease progression or death by 40% (HR=0.60 [95% CI: 0.50-0.72]; p<0.0001), with a median PFS of 6.6 months (95% CI: 5.6-7.4; number of events=247) versus 3.8 months (95% CI: 3.6-5.0; number of events=238) for patients who received TPC. LENVIMA plus KEYTRUDA reduced the risk of death by 32% (HR=0.68 [95% CI: 0.56-0.84]; p =0.0001), with a median OS of 17.4 months (95% CI: 14.2-19.9; number of events=165) versus 12.0 months (95% CI: 10.8-13.3; number of events=203) for patients who received TPC. The secondary endpoint of ORR was 30.3% (95% CI: 25.5-35.5), with a CR rate of 5.2% and a PR rate of 25.1%, for patients who received LENVIMA plus KEYTRUDA versus 15.1% (95% CI: 11.5-19.3), with a CR rate of 2.6% and a PR rate of 12.5%, for patients who received TPC (ORR difference versus TPC: 15.2 percentage points: p<0.0001). For patients who responded, the median DOR was 9.2 months (range: 1.6-23.7) for patients who received LENVIMA plus KEYTRUDA versus 5.7 months (range: 0.0-24.2) for patients who received TPC.

In the all-comer population, in the LENVIMA plus KEYTRUDA arm (n=406), any grade treatment-emergent adverse events (TEAEs) led to discontinuation of LENVIMA in 30.8% of patients, of KEYTRUDA in 18.7% of patients, and of both in 14.0% of patients. In the TPC arm (n=388), any grade TEAEs led to discontinuation of chemotherapy in 8.0% of patients. Grade 5 TEAEs of any cause occurred in 5.7% of patients in the LENVIMA plus KEYTRUDA arm and in 4.9% of patients in the TPC arm. Grade ≥3 TEAEs occurred in 88.9% of patients in the LENVIMA plus KEYTRUDA arm and in 72.7% of patients in the TPC arm. In the LENVIMA plus KEYTRUDA arm, the most common TEAEs of any grade occurring in at least 25% of patients were hypertension (64.0%), hypothyroidism (57.4%), diarrhea (54.2%), nausea (49.5%), decreased appetite (44.8%), vomiting (36.7%), weight decrease (34.0%), fatigue (33.0%), arthralgia (30.5%), proteinuria (28.8%), anemia (26.1%), constipation (25.9%), and urinary tract infection (25.6%). In the TPC arm, the most common TEAEs of any grade occurring in at least 25% of patients were anemia (48.7%), nausea (46.1%), neutropenia (33.8%), alopecia (30.9%), and fatigue (27.6%). Median treatment duration was 231 days (range: 1-817) with LENVIMA plus KEYTRUDA and 104.5 days (range: 1-785) with TPC.

Study 309/KEYNOTE-775 is the confirmatory trial for Study 111/KEYNOTE-146, which supported the U.S. Food and Drug Administration’s (FDA) 2019 accelerated approval of the LENVIMA plus KEYTRUDA combination for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation.

Study 309/KEYNOTE-775 is a multicenter, randomized, open-label, Phase 3 trial (ClinicalTrials.gov, NCT03517449(New Window)) evaluating LENVIMA in combination with KEYTRUDA in patients with advanced endometrial cancer following one prior platinum-based regimen in any setting. The dual primary endpoints are PFS, as assessed by BICR per RECIST v1.1, and OS. Select secondary endpoints include ORR by BICR per RECIST v1.1 and safety/tolerability. Of the 827 patients enrolled, 697 patients had tumors that were pMMR, and 130 patients had tumors that were dMMR. Patients were randomized 1:1 to receive LENVIMA (20 mg orally once daily) in combination with KEYTRUDA (200 mg intravenously [IV] every three weeks) for up to 35 cycles (approximately two years); or chemotherapy treatment of physician’s choice (TPC) of either doxorubicin 60 mg/m2 IV every three weeks for up to a maximum cumulative dose of 500 mg/m2 or paclitaxel 80 mg/m2 IV on a 28-day cycle [three weeks of receiving weekly paclitaxel and one week of not receiving paclitaxel]).

About Endometrial Cancer1,2,3,4,5

Endometrial cancer begins in the inner lining of the uterus, which is known as the endometrium and is the most common type of cancer in the uterus. In 2020, it was estimated there were more than 417,000 new cases and more than 97,000 deaths from uterine body cancers worldwide (these estimates include both endometrial cancers and uterine sarcomas; more than 90% of uterine body cancers occur in the endometrium, so the actual numbers for endometrial cancer cases and deaths are slightly lower than these estimates). In Japan, there were more than 17,000 new cases of uterine body cancer and more than 3,000 deaths from the disease in 2020. In the U.S., it is estimated there will be more than 66,000 new cases of uterine body cancer and nearly 13,000 deaths from the disease in 2021. The five-year survival rate for metastatic endometrial cancer (stage IV) is estimated to be approximately 17%.

About LENVIMA (lenvatinib) Capsules

LENVIMA, discovered and developed by Eisai, is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. In syngeneic mouse tumor models, lenvatinib decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone. Currently, LENVIMA has been approved for monotherapy as a treatment for thyroid cancer in over 70 countries including Japan, in Europe, China and in Asia, and in the U.S. for radioiodine-refractory differentiated thyroid cancer. In addition, Lenvima has been approved for monotherapy as a treatment for unresectable hepatocellular carcinoma in over 65 countries including Japan, the United States, in Europe, China and in Asia. It is also approved in combination with everolimus as a treatment for renal cell carcinoma following prior antiangiogenic therapy in over 60 countries, including the United States, in Europe and Asia. In Europe, the agent was launched under the brand name Kisplyx for renal cell carcinoma. In addition, it is approved in combination with KEYTRUDA as a treatment for advanced endometrial cancer that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation in over 10 countries including the United States, Canada and Australia. Continued approval for this indication is contingent upon verification and description of clinical benefit in the confirmatory trials.

About KEYTRUDA (pembrolizumab) Injection, 100mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck & Co., Inc., Kenilworth, N.J., U.S.A. has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,400 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

On March 19, 2021 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that the first presentation of data from the randomized, Phase 3 ARIEL4 study of Rubraca (rucaparib) will take place today in an oral presentation at the Society of Gynecologic Oncology Virtual Annual Meeting on Women’s Cancer (SGO) (Press release, Clovis Oncology, MAR 19, 2021, View Source [SID1234576898]). The data demonstrate that Rubraca significantly improves PFS compared to standard-of-care chemotherapy, including platinum-based chemotherapy, among patients with advanced, relapsed ovarian cancer and a deleterious BRCA mutation who have received two or more prior lines of chemotherapy.

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"Data from the ARIEL4 study meaningfully enhance our understanding about the role of Rubraca among women with BRCA mutation-positive relapsed ovarian cancer, as well as the clinical relevance of BRCA reversion mutations," said Dr. Rebecca Kristeleit, Co-Coordinating Investigator of ARIEL4 and Consultant Medical Oncologist, Guy’s and St Thomas’ NHS Foundation Trust, London, UK. "This is important because women with more advanced disease have fewer treatment options, and it is increasingly important to understand how specific mutations affect treatment outcomes."

Dr. Kristeleit will present "Rucaparib versus chemotherapy in patients with advanced, relapsed ovarian cancer and a deleterious BRCA mutation: efficacy and safety from ARIEL4, a randomized phase 3 study" today during the SGO Scientific Plenary I: Innovation and Progress in Gynecologic Oncology session from 2:35 pm – 3:45 pm CT. The presentation can also be viewed at View Source starting today at 2:35 pm CT.

The ARIEL4 study (NCT02855944) is a Phase 3 multicenter, randomized study evaluating Rubraca versus chemotherapy in fully platinum-sensitive, partially platinum-sensitive and platinum-resistant patients with relapsed ovarian cancer and a BRCA mutation (inclusive of germline and/or somatic) who have received two or more prior lines of chemotherapy. The primary endpoint of the study is investigator-assessed PFS, with a step-down analysis from the primary efficacy population (if significant) to the intent-to-treat (ITT) population.

The study enrolled 349 women in Europe, Israel and North and South America. The primary efficacy population (n=325) comprised the group of patients with a deleterious tumor BRCA mutation and excluded those with a BRCA reversion mutation as determined by a blood test. The rucaparib arm in this population (n=220) achieved statistical significance over the chemotherapy arm (n=105) for the primary endpoint of PFS with a hazard ratio of 0.64 (p=0.001). The median PFS for the patients in the efficacy population treated with rucaparib was 7.4 months versus 5.7 months among those who received chemotherapy.

Additionally, in the ITT population (n=349), the rucaparib arm (n=233) achieved statistical significance over the chemotherapy arm (n=116) for the primary endpoint of PFS with a hazard ratio of 0.67 (p=0.002). The median PFS for the patients in the ITT population treated with rucaparib was 7.4 months versus 5.7 months among those who received chemotherapy.

Adverse events were consistent with the known safety profiles of Rubraca and chemotherapy. The most common (>5%) treatment-emergent ≥grade 3 adverse events (TEAEs) among all patients treated with rucaparib (n=232) in the ARIEL4 study were anemia/decreased hemoglobin (22%), neutropenia/decreased absolute neutrophil count (10%), asthenia/fatigue (8%), thrombocytopenia/decreased platelets (8%), and increased ALT/AST (8%).

"The ARIEL4 data add to the growing scientific understanding about the clinical utilization of Rubraca compared to chemotherapy, including platinum-based chemotherapy, for women diagnosed with BRCA mutation-positive advanced ovarian cancer," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We remain committed to expanding treatment options for patients living with cancer and are pleased to share these data with physicians and their patients to help improve outcomes for women with ovarian cancer."

According to the American Cancer Society, an estimated more than 21,000 women will be diagnosed with ovarian cancer in the United States and there will be an estimated nearly 14,000 deaths from ovarian cancer in 2021, and according to GLOBOCAN in 2020, an estimated 66,000 women in Europe are diagnosed each year with ovarian cancer, and ovarian cancer is among those cancers with the highest rate of deaths. According to the American Cancer Society, more than 75% of women are diagnosed with ovarian cancer at an advanced stage, and patients who are diagnosed with advanced ovarian cancer have a 70-95% chance of recurrence according to the Ovarian Cancer Research Alliance.

About Rubraca (rucaparib)

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca Ovarian Cancer U.S. FDA Approved Indications

Rubraca is indicated for the maintenance treatment of adult women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Rubraca is indicated for the treatment of adult women with a deleterious BRCA mutation (germline and/or somatic)-associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) have occurred in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1146 treated patients, MDS/AML occurred in 20 patients (1.7%), including those in long term follow-up. Of these, 8 occurred during treatment or during the 28 day safety follow-up (0.7%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 53 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA damaging agents.

Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.

Based on its mechanism of action and findings from animal studies, Rubraca can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca.

Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1-4) were nausea (76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%), constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia (29%), nasopharyngitis/upper respiratory tract infection (29%), stomatitis (28%), decreased appetite (23%), and neutropenia (20%).

Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%; Grade 1-4) were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea (21%), and thrombocytopenia (21%).

Co-administration of rucaparib can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring.

Because of the potential for serious adverse reactions in breast-fed children from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks after the last dose.

Click here or full Prescribing Information and additional Important Safety Information.

Rubraca (rucaparib) European Union (EU) authorized use and Important Safety Information

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rubraca is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with ≥2 prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Efficacy of Rubraca as treatment for relapsed or progressive epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) has not been investigated in patients who have received prior treatment with a PARP inhibitor. Therefore, use in this patient population is not recommended.

Summary warnings and precautions:

Hematological toxicity

During treatment with Rubraca, events of myelosuppression (anemia, neutropenia, thrombocytopenia) may be observed and are typically first observed after 8–10 weeks of treatment with Rubraca. These reactions are manageable with routine medical treatment and/or dose adjustment for more severe cases. Complete blood count testing prior to starting treatment with Rubraca, and monthly thereafter, is advised. Patients should not start Rubraca treatment until they have recovered from hematological toxicities caused by previous chemotherapy (CTCAE grade ≥1).

Supportive care and institutional guidelines should be implemented for the management of low blood counts for the treatment of anemia and neutropenia. Rubraca should be interrupted or dose reduced according to Table 1 (see Posology and Method of Administration [4.2] of the Summary of Product Characteristics [SPC]) and blood counts monitored weekly until recovery. If the levels have not recovered to CTCAE grade 1 or better after 4 weeks, the patient should be referred to a hematologist for further investigations.

MDS/AML

MDS/AML, including cases with fatal outcome, have been reported in patients who received Rubraca. The duration of therapy with Rubraca in patients who developed MDS/AML varied from less than 1 month to approximately 28 months.

If MDS/AML is suspected, the patient should be referred to a hematologist for further investigations, including bone marrow analysis and blood sampling for cytogenetics. If, following investigation for prolonged hematological toxicity, MDS/AML is confirmed, Rubraca should be discontinued.

Photosensitivity

Photosensitivity has been observed in patients treated with Rubraca. Patients should avoid spending time in direct sunlight because they may burn more easily during Rubraca treatment; when outdoors, patients should wear a hat and protective clothing, and use sunscreen and lip balm with sun protection factor of 50 or greater.

Gastrointestinal toxicities

Gastrointestinal toxicities (nausea and vomiting) are frequently reported with Rubraca, and are generally low grade (CTCAE grade 1 or 2), and may be managed with dose reduction (refer to Posology and Method of Administration [4.2], Table 1 of the SPC) or interruption. Antiemetics, such as 5-HT3 antagonists, dexamethasone, aprepitant and fosaprepitant, can be used as treatment for nausea/vomiting and may also be considered for prophylactic (i.e. preventative) use prior to starting Rubraca. It is important to proactively manage these events to avoid prolonged or more severe events of nausea/vomiting which have the potential to lead to complications such as dehydration or hospitalization.

Embryofetal toxicity

Rubraca can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings from animal studies. In an animal reproduction study, administration of Rubraca to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at exposures below those in patients receiving the recommended human dose of 600 mg twice daily (see Preclinical Safety Data [5.3] of the SPC).

Pregnancy/contraception

Pregnant women should be informed of the potential risk to a fetus. Women of reproductive potential should be advised to use effective contraception during treatment and for 6 months following the last dose of Rubraca (see section 4.6 of the SPC). A pregnancy test before initiating treatment is recommended in women of reproductive potential.

On March 18, 2021 Xspray Pharma reported an update on the upcoming pivotal study with its improved version of Sprycel (dasatinib), based on the company’s HyNap-Dasa formulation (Press release, Xspray, MAR 18, 2021, View Source [SID1234650109]). The study has been initiated and the dosing for the bioequivalence study will start in the second quarter with the aim to submit an application for market approval in accordance with the 505(b)(2) procedure in the second half of 2021.

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In parallel with its development of generic protein kinase inhibitors (PKIs) based on the company’s amorphous technology platform, Xspray Pharma also develops improved versions of the original pharmaceutical agents. The overall strategy for HyNap-Dasa is unchanged and based on fastest possible route to market for;

a generic (ANDA) HyNap-Dasa version of Sprycel during the patent window
an improved (505(b)(2)) HyNap-Dasa version of Sprycel with relevant medical benefits
The improved version of Sprycel is designed to offer patients suffering from acute lymphocytic leukemia (ALL) and chronic myeloid leukemia (CML) an improved quality of life by enabling treatment with protein pump inhibitors, PPIs (omeprazole), together with the life-saving treatment with dasatinib. This improved version is also designed to overcome the issue with patients with low or no uptake as demonstrated for Sprycel in earlier bioequivalence studies. The improved version will also be administrated at a significantly lower strength compared to Sprycel and reduce variability. With these improvements HyNap-Dasa will offer meaningful medical benefits for patients and caregivers.

"Almost a third of the patient population has a need for PPIs. I hope that this improved version will offer them a treatment where you can treat cancer and for example ulcer at the same time. We will use the same formulation of HyNap-Dasa as was used in the bioequivalence studies that we ran in 2020 but giving a lower strength of HyNap-Dasa compared to Sprycel. Since we have already tested the formulation in healthy volunteers it is a de-risked study without significantly affecting our financial situation. We have a very robust set of pharmacokinetic data supporting the design of this study which reduces the risk considerably.", says Per Andersson, CEO Xspray Pharma.

The pivotal bioequivalence study aims to demonstrate that Xspray Pharma’s improved version can be administrated using significantly lower strength compared to the original drug and still obtain the same bioavailability. Previous studies with this formulation have already showed no food interaction and no drug-drug interaction with PPI, omeprazole.

"With our multiple pathway strategy, we are now in parallel developing both an improved and a generic version. Thereby we will be able to challenge the original product’s market position and create substantial value for the company and its shareholders. Our clinical work on the generic version of dasatinib continues according to plan. We are currently running a bioequivalence study with a slightly modified formulation and we expect data from this study in April. As a risk mitigating strategy, we are prepared to start studies with an additional formulation that has shown encouraging data in laboratory tests," concludes Per Andersson.

In 2020 Sprycel sold worldwide for USD 2,140 million of which USD 1,295 million was in the US. Xspray Pharma is aiming for market approval for the improved version of dasatinib in US, Europe, and all other major markets.

On March 18, 2021 Swedish-based Newbury Pharmaceuticals AB, a hybrid pharmaceutical company for specialty prescription drugs, innovation and brands, has successfully completed its Series A funding round of 25 MSEK (Press release, Newbury Pharmaceuticals, MAR 18, 2021, View Source [SID1234632241]).

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The oversubscribed Series A financing brings 25 MSEK from selected strategic investors. Proceeds from the funding round will support to continue building a pipeline of proprietary and licensed products. The portfolio strategy includes niche and value-added small molecules, product development based on peptide technology as well as biosimilars in a variety of therapeutic categories.

"We have the ambition to become the local champion and alternative partner to the multinationals. We strive to have a positive impact in the society, bring products and technology that contribute to the overall healthcare system and patient’s wellbeing – and give our partner the local attention they deserve" says Karl Karlsson, Founder & CEO.

On March 18, 2021 Shanghai Fosun Pharmaceutical (Group) Co., Ltd. ("Fosun Pharma"; stock code: 600196.SH; 02196.HK) reported that its subsidiary YaoPharma Co., Ltd. ("YaoPharma") had recently received the approval from the NMPA regarding the clinical trial for the YP01001 capsules (the "Investigational New Drug") for the treatment of advanced solid tumors (Press release, Fosun Pharma, MAR 18, 2021, View Source [SID1234626451]).

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The Investigational New Drug is an innovative small molecule chemical drug intended for the treatment of advanced solid tumors (including, among others, liver cancer and gastric cancer). YaoPharma plans to conduct Phase I clinical trial for the Investigational New Drug in China (excluding Hong Kong, Macao and Taiwan) recently after the conditions are available.

As of February 2021, Fosun Pharma has invested about RMB 33.66 million (unaudited) in the R&D of the Investigational New Drug at this stage.

Driven by innovation and R&D, Fosun Pharma continuously improves its drug R&D system based on the combination of generic and innovator drugs and builds international R&D platforms for small molecule innovator drugs, high-cost generic drugs, biologics and new technology-based therapies, etc.

In the future, the Company will continue to focus on clinical demands, increase its investment in R&D and improve innovation efficiency, so as to bring high-quality and affordable innovator drugs to patients.