On August 9, 2021 Mission Therapeutics ("Mission"), a drug discovery and development company focused on targeting the ubiquitin pathway, and AbbVie ("AbbVie")(NYSE: ABBV) reported progression of selected deubiquitylating enzyme (DUB) targets into the next phase of research in their neurodegenerative disease collaboration (Press release, Mission Bio, AUG 9, 2021, View Source [SID1234586152]).

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In the second major milestone of the Companies’ research and preclinical development collaboration, AbbVie has nominated two DUB targets to progress to the next stage of drug discovery. This selection follows supportive data from in vitro and in vivo Alzheimer’s and Parkinson’s disease models. As a result of the nomination, Mission will receive a milestone payment of $20 million from AbbVie.

Alzheimer’s and Parkinson’s diseases are the most common neurological disorders worldwide, with over 50 million people living with dementia and Alzheimer’s disease, and 10 million more with Parkinson’s. While there are treatments to help reduce symptoms, there are no treatments available to help stop or reverse progression.

Both Alzheimer’s and Parkinson’s are associated with the accumulation of misfolded, proteins in the brain, which are believed to cause impaired function and death of nerve cells. DUBs can help to maintain cell health by regulating the degradation of these proteins.

Under the terms of the agreement, first announced in 2018, Mission and AbbVie are collaborating to identify novel DUB targets and discover associated inhibitor compounds for neurodegenerative diseases. AbbVie has the option to gain exclusive rights to develop and commercialize inhibitors of selected DUB targets and will pay Mission success-based milestones as well as royalty payments for each commercialized product.

Commenting on the development, Dr Anker Lundemose, Mission’s CEO, said:

"We are delighted to have reached this next major milestone in our collaboration with AbbVie and receive the $20 million milestone – this represents a big step forward for Mission and further highlights DUBs as targets for drug development. The successful and timely progression of two DUB targets into the drug discovery phase is further validation of our platform. We look forward to the continuation of this great neurodegenerative disease collaboration."

Dr Eric Karran, Vice President, Neuroscience Discovery Research, AbbVie commented:

"There is an urgent need for treatments that can make tangible and lasting improvements to the lives of Alzheimer’s and Parkinson’s patients. Our collaboration with Mission has the potential to identify novel therapeutic options for neurodegenerative disorders. We have had a great experience working with Mission and are pleased to be able to continue to draw on their valued expertise as we enter the next phase of drug development."

On August 9, 2021 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca reported that Positive topline results from the head-to-head DESTINY-Breast03 phase 3 trial showed that ENHERTU (trastuzumab deruxtecan), the HER2 directed antibody drug conjugate (ADC), demonstrated superiority over trastuzumab emtansine (T-DM1) (Press release, Daiichi Sankyo, AUG 9, 2021, View Source [SID1234586151]).

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At a planned interim analysis, the Independent Data Monitoring Committee (IDMC) concluded that DESTINY-Breast03 met the primary endpoint of progression-free survival (PFS), showing a highly statistically significant and clinically meaningful improvement in PFS for patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

Breast cancer remains the most common cancer worldwide, with more than two million cases diagnosed in 2020, resulting in nearly 685,000 deaths globally.1 Approximately one in five cases of breast cancer are considered HER2 positive.2 Despite initial treatment with trastuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.3 More effective options are needed to further delay progression and extend survival.3,4,5

In DESTINY-Breast03, ENHERTU also showed a strong trend toward improved overall survival (OS) compared to T-DM1 in a key secondary endpoint, although the OS data are still immature. The safety profile of ENHERTU was consistent with previous clinical trials with no new safety concerns identified and no grade 4 or 5 treatment-related interstitial lung disease events.

"DESTINY-Breast03 is the first global phase 3 head-to-head trial of ENHERTU against an active control and supports the potential of this medicine to become the new standard of care for patients with HER2 positive metastatic breast cancer following treatment with trastuzumab and a taxane," said Ken Takeshita, MD, Global Head, Research and Development, Daiichi Sankyo. "We believe this specifically engineered ADC, with a highly sophisticated delivery system, is fulfilling its promise to reshape the treatment of HER2 positive metastatic breast cancer with the goal to move into earlier lines of treatment for HER2 positive breast cancer, as well as many other HER2 expressing tumor types across our broad clinical trial program."

"There is a continued need for new options and better outcomes for patients with HER2 positive metastatic breast cancer who often experience disease progression after initial treatment with available standards of care," said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. "These transformative progression-free survival results demonstrate the superiority of ENHERTU compared to T-DM1 and the encouraging safety data may open future opportunities to bring this benefit to patients in earlier treatment settings."

These data will be presented at an upcoming medical meeting and shared with health authorities.

About DESTINY-Breast03

DESTINY-Breast03 is a global, head-to-head, randomized, open-label, pivotal phase 3 trial evaluating the safety and efficacy of ENHERTU (5.4 mg/kg) versus T-DM1 in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

The primary efficacy endpoint of DESTINY-Breast03 is PFS based on blinded independent central review. Secondary efficacy endpoints include OS, objective response rate (ORR), duration of response (DOR), clinical benefit rate, PFS based on investigator assessment and safety.

DESTINY-Breast03 enrolled approximately 500 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

About HER2 Positive Breast Cancer

Breast cancer remains the most common cancer and is one of the leading causes of cancer-related deaths in women worldwide.1 More than two million cases of breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally.1 Approximately one in five cases of breast cancer are considered HER2 positive.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers.6 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.7

Despite initial treatment with trastuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression. More effective options are needed to further delay progression and extend survival.3,4,5

About ENHERTU

ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

ENHERTU (5.4 mg/kg) is approved in Canada, EU, Israel, Japan, UK and U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting based on the results from the DESTINY-Breast01 trial.

ENHERTU (6.4 mg/kg) is also approved in Israel, Japan and U.S. for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see the accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

About the ENHERTU Clinical Development Program

A comprehensive global development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

ENHERTU was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the "ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers," based on data from both the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of the targeted therapy advances of the year in non-small cell lung cancer (NSCLC) based on the interim results of the HER2 mutated cohort of the DESTINY-Lung01 trial.

In May 2020, ENHERTU received Breakthrough Therapy Designation in the U.S. for the treatment of patients with metastatic NSCLC whose tumors have a HER2 mutation and with disease progression on or after platinum-based therapy.

About the Daiichi Sankyo and AstraZeneca Collaboration

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan.

U.S. Important Safety Information for ENHERTU

Indications

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

Unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.
Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.
Contraindications

None.

Warnings and Precautions

Interstitial Lung Disease / Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.

Metastatic Breast Cancer

In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3).

Locally Advanced or Metastatic Gastric Cancer

In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21.0).

Neutropenia

Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level.

Metastatic Breast Cancer

In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU 5.4mg/kg, a decrease in neutrophil count was reported in 62% of patients. Sixteen percent had Grade 3 or 4 decrease in neutrophil count. Median time to first onset of decreased neutrophil count was 23 days (range: 6 to 547). Febrile neutropenia was reported in 1.7% of patients.

Locally Advanced or Metastatic Gastric Cancer

In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.

Left Ventricular Dysfunction

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure.

Embryo-Fetal Toxicity

ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.

Additional Dose Modifications

Thrombocytopenia

For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less. Reduce dose by one level.

Adverse Reactions

Metastatic Breast Cancer

The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (79%), white blood cell count decreased (70%), hemoglobin decreased (70%), neutrophil count decreased (62%), fatigue (59%), vomiting (47%), alopecia (46%), aspartate aminotransferase increased (41%), alanine aminotransferase increased (38%), platelet count decreased (37%), constipation (35%), decreased appetite (32%), anemia (31%), diarrhea (29%), hypokalemia (26%), and cough (20%).

Locally Advanced or Metastatic Gastric Cancer

The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma in DESTINY‑Gastric01. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg once every three weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) in the ENHERTU group and 2.8 months (range: 0.5 to 13.1) in the irinotecan/paclitaxel group.

Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%).

ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and hypokalemia. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (75%), white blood cell count decreased (74%), neutrophil count decreased (72%), lymphocyte count decreased (70%), platelet count decreased (68%), nausea (63%), decreased appetite (60%), anemia (58%), aspartate aminotransferase increased (58%), fatigue (55%), blood alkaline phosphatase increased (54%), alanine aminotransferase increased (47%), diarrhea (32%), hypokalemia (30%), vomiting (26%), constipation (24%), blood bilirubin increased (24%), pyrexia (24%), and alopecia (22%).

Use in Specific Populations

Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of ENHERTU.
Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
Geriatric Use: Of the 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (53%) as compared to younger patients (42%). Of the 125 patients with locally advanced or metastatic HER2‑positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients.
Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.
To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

About Daiichi Sankyo in Oncology

The oncology portfolio of Daiichi Sankyo is powered by our team of world-class scientists that push beyond traditional thinking to create transformative medicines for people with cancer. Anchored by our DXd antibody drug conjugate (ADC) technology, our research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in the U.S. We also work alongside leading academic and business collaborators to further advance the understanding of cancer as Daiichi Sankyo builds towards our ambitious goal of becoming a global leader in oncology by 2025.

On August 9, 2021 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the pivotal Phase III POLARIX trial investigating Polivy (polatuzumab vedotin) in combination with Rituxan (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) versus Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) met its primary endpoint by demonstrating significantly improved and clinically meaningful progression-free survival in people with previously untreated diffuse large B-cell lymphoma (DLBCL) (Press release, Genentech, AUG 9, 2021, View Source [SID1234586150]). Safety outcomes were consistent with those seen in previous trials.

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"Since 40% of people with DLBCL relapse after initial therapy, achieving meaningful treatment effects in the front-line setting has the potential to be transformative," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "This Polivy regimen is the first in two decades to improve progression-free survival in DLBCL compared to the standard of care, and we look forward to sharing these results with health authorities to bring this important potential new treatment option to patients as soon as possible."

Today’s POLARIX results will be presented at an upcoming medical meeting and submitted to health authorities as part of Genentech’s commitment to transforming the treatment of DLBCL by providing options tailored to patient and healthcare professional needs. Genentech would like to thank all investigators, academic partners and people with DLBCL who participated in the study.

Currently, Polivy is used as an off-the-shelf, fixed-duration treatment option in the relapsed or refractory (R/R) DLBCL setting, and is approved in combination with bendamustine and Rituxan for the treatment of R/R DLBCL in more than 60 countries worldwide, including in the EU and in the U.S. Genentech continues to explore areas of unmet need where Polivy has the potential to deliver benefit, with ongoing studies investigating combinations of Polivy with the CD20xCD3 T cell-engaging bispecific antibodies mosunetuzumab and glofitamab, with Venclexta (venetoclax), which is being developed by AbbVie and Genentech, and with Rituxan in combination with gemcitabine and oxaliplatin in the Phase III POLARGO study.

About the POLARIX study

POLARIX [NCT03274492] is an international Phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy (polatuzumab vedotin) plus Rituxan (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) versus Rituxan, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Eight-hundred and seventy-nine patients were randomized 1:1 to receive either Polivy plus R-CHP plus a vincristine placebo for six cycles, followed by Rituxan for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of Rituxan. The primary outcome measure is progression-free survival as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma. POLARIX is being conducted in collaboration with The Lymphoma Study Association (LYSA) and The Lymphoma Academic Research Organisation (LYSARC).

About Polivy (polatuzumab vedotin-piiq)

Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B cells, an immune cell impacted in some types of non-Hodgkin’s lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells. Polivy is being developed by Genentech using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.

About DLBCL

DLBCL is the most common form of non-Hodgkin’s lymphoma (NHL), accounting for about one in three cases of NHL. DLBCL is an aggressive (fast-growing) type of NHL. While it is generally responsive to treatment in the frontline, as many as 40% of patients will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short. Approximately 150,000 people worldwide are estimated to be diagnosed with DLBCL each year.

Polivy U.S. Indication

Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat diffuse large B-cell lymphoma in adults who have progressed after at least two prior therapies.

The accelerated approval of Polivy is based on a type of response rate. There are ongoing studies to confirm the clinical benefit of Polivy.

Important Safety Information

Possible serious side effects

Everyone reacts differently to Polivy therapy, so it’s important to know what the side effects are. Some people who have been treated with Polivy have experienced serious to fatal side effects. A patient’s doctor may stop or adjust a patient’s treatment if any serious side effects occur. Patients must contact their healthcare team if there are any signs of these side effects.

Nerve problems in arms and legs: This may happen as early as after the first dose and may worsen with every dose. If a patient already has nerve pain, Polivy may make it worse. The patient’s doctor will monitor for signs and symptoms, such as changes in sense of touch, numbness or tingling in hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to walking patterns
Infusion-related reactions: A patient may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of the infusion
Infections: Patients should contact their healthcare team, if they experience a fever of 100.4°F or higher, chills, cough, or pain during urination. Also, a patient’s doctor may give medication before giving Polivy, which may prevent some infections, and monitor blood counts throughout treatment with Polivy. Treatment with Polivy can cause severe low blood cell counts
Rare and serious brain infections: A patient’s doctor will monitor the patient closely for signs and symptoms of these types of infections. Patients should contact their doctor if they experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes
Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy
Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of the skin or the white part of the eyes. Patients may be at higher risk if they already have liver problems or are taking other medication
Side effects seen most often

The most common side effects during treatment were

Low blood cell counts (platelets, red blood cells, white blood cells)
Nerve problems in arms and legs
Tiredness or lack of energy
Diarrhea
Nausea
Fever
Decreased appetite
Infections
Polivy may not be for everyone. A patient should talk to their doctor if they are

Pregnant or may be pregnant: Data have shown that Polivy may harm an unborn baby
Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for at least 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for at least 5 months after their last Polivy treatment
Breastfeeding: Women should not breastfeed while taking Polivy and for at least 2 months after the last dose
These may not be all the side effects. Patients should talk to their healthcare provider for more information about the benefits and risks of Polivy treatment.

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the full Prescribing Information for additional Important Safety Information.

About Genentech in Hematology

For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit View Source

On August 9, 2021 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported that it has received Promising Innovative Medicine (PIM) designation from the UK Medicines and Healthcare products Regulatory Agency (MHRA) for AUTO1 (obecabtagene autoleucel, obe-cel), the company’s CAR T cell therapy being investigated in the ongoing FELIX Phase 1b/2 study in relapsed/refractory (r/r) adult B-cell Acute Lymphocytic Leukemia (ALL) in patients 18 years and older (Press release, Autolus, AUG 9, 2021, View Source [SID1234586149]).

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"PIM designation is a recognition of obe-cel as a promising candidate for the Early Access to Medicines Scheme (EAMS) in the UK for the treatment of adult patients with r/r ALL, a life-threatening condition with high unmet need," said Dr. Christian Itin, chief executive officer of Autolus.

About PIM
PIM designations are given to medicinal products that are likely to offer a major advantage for patients. For the MHRA to grant a PIM Designation, the product must meet each of the following three criteria:*

Criterion 1: The conditions should be life-threatening or seriously debilitating with high unmet need, meaning there is no method of treatment, diagnosis or prevention available, or existing methods have serious limitations
Criterion 2: The medicinal product is likely to offer major advantage over methods currently used in the UK. Preliminary evidence should be submitted based on both non-clinical and clinical data
Criterion 3: The potential adverse effects of the medicinal product are likely to be outweighed by the benefits, allowing for the reasonable expectation of a positive benefit risk balance

On August 9, 2021 Sesen Bio (Nasdaq: SESN), a late-stage clinical company developing targeted fusion protein therapeutics for the treatment of patients with cancer, reported operating results for the second quarter ended June 30, 2021 . The Biologics License Application (BLA) for the Company’s lead program, Vicineum for the treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC), is currently under Priority Review with the US Food and Drug Administration (FDA) with a target Prescription Drug User Fee Act (PDUFA) date of August 18, 2021.

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"We are excited about the regulatory progress we are making across our global markets," said Dr. Thomas Cannell, president and chief executive officer of Sesen Bio. "We remain focused on executing a world-class launch in the US if Vicineum is approved, and we also continue to support our partners outside of the United States, as part of our commitment to deliver a therapy we believe can improve patient outcomes globally while reducing overall healthcare costs for patients."

US and Outside of the US (OUS) Regulatory Update

US:

On July 13, 2021, Sesen Bio participated in a productive Late-Cycle Meeting with the FDA regarding the BLA for Vicineum for the treatment of BCG-unresponsive NMIBC. In the meeting, the FDA confirmed that there is no Advisory Committee meeting planned at this time, and that no post-marketing requirements, including a confirmatory trial, have been identified at this time. Also in the meeting, the Company and the FDA discussed remaining questions related to manufacturing facility inspections, product quality information requests and additional information related to chemistry, manufacturing and controls (CMC), and a timeline to submit additional supporting information was agreed upon. The Company believes it remains on track for an FDA decision on its BLA for Vicineum by the target PDUFA date of August 18, 2021.
Europe:

In Europe, the Company believes it remains on track for potential approval of Vysyneum in 2022. The Company has received the Day 80 and Day 120 questions from the European Medicines Agency (EMA) and is responding to inquiries and providing supporting information as part of the official review process.
China:

On July 20, 2021, Sesen Bio and Qilu Pharmaceutical, the Company’s partner in Greater China, announced that the first patient had been enrolled in China in the clinical trial to assess the efficacy and safety of Vicineum in patients with BCG-unresponsive NMIBC. The trial, which plans to enroll approximately 53 patients with carcinoma in situ (CIS), is being run at the sole cost of Qilu Pharmaceutical. If the trial is successful, Qilu Pharmaceutical anticipates submission of the product market application for Vicineum in China in 2022, with potential approval expected in 2023.
Middle East and North Africa (MENA):

The Company continues to work closely with its partner in MENA, Hikma Pharmaceuticals, to submit marketing authorization applications for Vicineum in 2021 in seven key markets in the region: Kingdom of Saudi Arabia, Jordan, Morocco, Egypt, Lebanon, Kuwait and Algeria. These markets represent a significant opportunity, with some of the most advanced healthcare systems and largest economies in the MENA region. The Company believes it is on track for potential market approvals to begin in the region in 2022.
Business Development Update

On June 1, 2021, the Company entered into a global supply agreement with Qilu Pharmaceutical to become part of the manufacturing network for global commercial supply of Vicineum drug substance and drug product. This was an expansion of the initial commercial manufacturing and supply framework agreement entered into by Sesen Bio and Qilu Pharmaceutical in December 2020, and sets specific terms such as capacity, forecasts, pricing and product delivery. Along with existing world-class supply partners, Sesen Bio expects the global supply agreement with Qilu Pharmaceutical will enable the Company to meet anticipated significant global demand for Vicineum.
On August 5, 2021, Sesen Bio announced it had entered into a licensing agreement with Eczacibasi Pharmaceuticals Marketing (EIP) for the registration and commercialization of Vicineum in Turkey. Under the terms of the licensing agreement, Sesen Bio will receive an upfront payment of $1.5 million, is eligible to receive additional regulatory and commercial milestone payments and is also entitled to receive a 30% royalty on net sales in Turkey. EIP was granted an exclusive license to register and commercialize Vicineum for the treatment of BCG-unresponsive NMIBC in Turkey, where bladder cancer is the sixth most commonly diagnosed cancer and 11th most common cause of death. This agreement represents the third OUS partnership that Sesen Bio has entered to date.
Commercial Planning Update

Sesen Bio completed its commercial build phase in preparation for the anticipated launch of Vicineum, if approved, in the US, and has advanced to the implementation phase that will commence promptly, if approved, and will focus on executing the Company’s commercial strategy for Vicineum. The Company has completed the hiring of ~25 talented internal employees to support the Company cross-functionally, as well as the hiring of 35 sales representatives as part of the contract sales organization who will target approximately 2,000 high-prescribers of BCG to drive awareness, trial and adoption of Vicineum for the treatment of patients with BCG-unresponsive NMIBC.
In addition to building its sales force, as part of the Sesen Bio national speaker programs, the Company has identified and commenced training of 14 key opinion leader (KOL) speakers to educate their peers on Vicineum for the treatment of BCG-unresponsive NMIBC, if approved. Upon product availability, the Company will utilize a two-pronged market access and reimbursement strategy to ensure maximum coverage for Vicineum.

Promotional efforts will begin immediately upon the anticipated approval of Vicineum in the US, and the Company expects Vicineum product to be available to physicians and patients in the fourth quarter of 2021.

Results of market research conducted by the Company show that when given the choice between the product profile of Vicineum, based on Phase III clinical trial data1, and the product profile of Keytruda, physicians will choose Vicineum over 80% of the time. This data highlights urologists’ preferences that the Company believes spans clinical, emotional and economic reasons to prescribe Vicineum. If approved by the FDA, the Company believes Vicineum could be a best-in-class treatment option for patients, and a critical step in Sesen Bio realizing its mission to save and improve the lives of patients with cancer.
[1]The Phase III clinical data are based on the data submitted in the BLA on December 18, 2020 and are currently under review by the FDA. Final efficacy and safety data are pending.

Second Quarter 2021 Financial Results

Cash Position: Cash, cash equivalents and restricted cash were $151.1 million as of June 30, 2021, compared to $55.4 million as of December 31, 2020.
R&D Expenses: Research and development expenses for the second quarter of 2021 were $7.2 million compared to $4.6 million for the same period in 2020. The increase of $2.7 million was due to increased costs associated with technology transfer and manufacturing ($1.0 million), professional services in support of regulatory activity ($0.7 million), employee-related compensation ($0.7 million), and other increases ($0.3 million).
G&A Expenses: General and administrative expenses for the second quarter of 2021 were $6.8 million compared to $3.3 million for the same period in 2020. The increase of $3.5 million was due primarily to increases in sales and marketing expense for Vicineum pre-commercial launch planning ($1.6 million), employee-related compensation driven by increased headcount as part of the commercial build ($1.3 million), and other increases for commercial launch preparation ($0.6 million).
Net Loss: Net loss was $25.4 million, or $0.15 per share, for the second quarter of 2021, compared to net loss of $26.3 million, or $0.24 per share, for the second quarter of 2020. The change was attributable to license revenue recognized ($2.2 million), offset by higher operating expenses ($1.3 million).
About Vicineum

Vicineum, a locally administered fusion protein, is Sesen Bio’s lead product candidate being developed for the treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). Vicineum is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A. Vicineum is constructed with a stable, genetically engineered peptide tether to ensure the payload remains attached to the antibody binding fragment until it is internalized by the cancer cell. This fusion protein design is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical trials conducted by Sesen Bio, EpCAM has been shown to be overexpressed in NMIBC cells with minimal to no EpCAM expression observed on normal bladder cells. Sesen Bio is currently in the follow-up stage of a Phase 3 registration trial in the US for the treatment of BCG-unresponsive NMIBC. In February 2021, the FDA accepted the Company’s BLA file for Vicineum for the treatment of BCG-unresponsive NMIBC and granted the application Priority Review with a target PDUFA date of August 18, 2021. Additionally, Sesen Bio believes that cancer cell-killing properties of Vicineum promote an anti-tumor immune response that may potentially combine well with immuno-oncology drugs, such as checkpoint inhibitors. For this reason, the activity of Vicineum in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.