publication date: Jan. 5, 2018

Drugs and Targets

FDA approves Perjeta in adjuvant breast cancer

FDA has approved Genentech’s Perjeta (pertuzumab), in combination with Herceptin (trastuzumab) and chemotherapy (the Perjeta-based regimen), for adjuvant treatment of HER2-positive early breast cancer at high risk of recurrence.

Genentech is a member of the Roche Group.

Patients should receive the adjuvant Perjeta-based regimen for one year (up to 18 cycles).

FDA has also converted the previously granted accelerated approval of the Perjeta-based regimen to full approval for neoadjuvant treatment of HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than two centimeters in diameter or node-positive). People receiving the neoadjuvant Perjeta-based regimen should continue Perjeta and Herceptin after surgery to complete one year of treatment.

The FDA-approved use of the Perjeta-based regimen for adjuvant treatment of HER2-positive EBC at high risk of recurrence is based on results of the phase III APHINITY study. At the time of the primary analysis with a median of 45.4 months follow-up:

  • In the overall study population, Perjeta, Herceptin and chemotherapy significantly reduced the risk of invasive breast cancer recurrence or death by 18 percent compared to Herceptin and chemotherapy alone (HR=0.82, 95% CI 0.67-1.00, p=0.047). 

  • High-risk patients included patients such as those with lymph node-positive or hormone receptor-negative breast cancer. The subgroup results were as follows:

    • Lymph node-positive subgroup (HR=0.77, 95% CI 0.62-0.96)

    • Hormone receptor-negative subgroup (HR=0.76, 95% CI 0.56-1.04)

    • Hormone receptor-positive subgroup (HR=0.86, 95% CI 0.66-1.13)

    • Lymph node-negative subgroup (HR=1.13, 95% CI 0.68-1.86)

The most common severe (grade III-IV) side effects with the Perjeta-based regimen are low levels of white blood cells with or without a fever, diarrhea, decrease in certain types of white blood cells, decrease in red blood cells, fatigue, nausea and mouth blisters or sores. The most common side effects are diarrhea, nausea, hair loss, fatigue, nerve damage and vomiting.

The supplemental Biologics License Application for the Perjeta-based regimen for adjuvant treatment of HER2-positive EBC was granted Priority Review, a designation given to medicines the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.

Perjeta is also approved for use in combination with Herceptin and docetaxel in people who have HER2-positive breast cancer that has spread to different parts of the body and who have not received anti-HER2 therapy or chemotherapy for metastatic breast cancer.

APHINITY (Adjuvant Pertuzumab and Herceptin IN Initial TherapY in Breast Cancer, NCT01358877/ BO25126/ BIG 4-11) is an international, phase III, randomized, double-blind, placebo-controlled, two-arm study evaluating the efficacy and safety of Perjeta plus Herceptin and chemotherapy compared to Herceptin and chemotherapy as adjuvant therapy in 4,805 people with operable HER2-positive EBC.

The primary efficacy endpoint of the APHINITY study is invasive disease-free survival, which in this study is defined as the time a patient lives without return of invasive breast cancer at any site or death from any cause after adjuvant treatment. Secondary endpoints include cardiac and overall safety, overall survival, disease-free survival and health-related quality of life. The study will continue to follow participants for ten years.


FDA approves Cabometyx for previously untreated advanced renal cell carcinoma

FDA approved Cabometyx (cabozantinib) tablets for the expanded indication of patients with advanced renal cell carcinoma.

FDA’s priority review and approval of Cabometyx was based on results from the randomized phase II CABOSUN trial in patients with previously untreated RCC, which demonstrated a statistically significant and clinically meaningful improvement in progression-free survival versus sunitinib, a current standard of care.

The label expansion follows the initial FDA approval of Cabometyx in April 2016 for the treatment of patients with advanced RCC who have previously received anti-angiogenic therapy.

The expanded approval of Cabometyx is based on results of the phase II CABOSUN trial, which met its primary endpoint of improving PFS. According to the independent radiology review committee analysis of the data, Cabometyx, sponsored by Exelixis Inc., demonstrated a clinically meaningful and statistically significant 52 percent reduction in the rate of disease progression or death (HR 0.48, 95% CI 0.31-0.74, two-sided P=0.0008). Median PFS for Cabometyx was 8.6 months versus 5.3 months for sunitinib, corresponding to a 3.3 month (62 percent) improvement.

All causality grade III or IV adverse reactions occurred in 68 percent of patients receiving  Cabometyx and 65 percent of patients receiving sunitinib.

The most frequent all causality Grade 3-4 adverse reactions (≥5 percent) in patients treated with Cabometyx were hypertension, diarrhea, hyponatremia, hypophosphatemia, palmar-plantar erythrodysesthesia, fatigue, increased ALT, decreased appetite, stomatitis, pain, hypotension, and syncope. Twenty-one percent of patients in the Cabometyx arm compared to 22 percent of patients receiving sunitinib discontinued treatment due to adverse events.

On May 23, 2016, Exelixis announced that CABOSUN met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS compared with sunitinib in patients with advanced intermediate- or poor-risk RCC as determined by investigator assessment.

The CABOSUN study was conducted by The Alliance for Clinical Trials in Oncology and was sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program under the Cooperative Research and Development Agreement withExelixis for the development of cabozantinib.

These results were first presented by Toni Choueiri at the European Society for Medical Oncology 2016 Congress, and published in the Journal of Clinical Oncology (Choueiri, JCO, 2016).

In June 2017, a blinded independent radiology review committee confirmed that cabozantinib provided a clinically meaningful and statistically significant improvement in the primary efficacy endpoint of investigator-assessed PFS. Results from the IRC review were presented by Dr. Toni Choueiri at the ESMO 2017 Congress.

CABOSUN was a randomized, open-label, active-controlled phase II trial that enrolled 157 patients with advanced RCC determined to be intermediate- or poor-risk by the IMDC criteria. Patients were randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, 4 weeks on followed by 2 weeks off). 

The primary endpoint was PFS. Secondary endpoints included overall survival, objective response rate and safety. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2 and had to be intermediate or poor risk per the IMDC criteria (Heng, JCO, 2009). Prior systemic treatment for RCC was not permitted.


FDA approves Pfizer’s Bosulif (bosutinib) for newly-diagnosed Ph+ CML

FDA approved a supplemental New Drug Application to expand the indication for Bosulif (bosutinib) to include adult patients with newly-diagnosed chronic phase Philadelphiachromosome-positive chronic myelogenous leukemia.

The sNDA was reviewed and approved under the FDA’s Priority Review and accelerated approval programs based on molecular and cytogenetic response rates. Continued approval for this indication may be contingent upon verification and confirmation of clinical benefit in an ongoing long-term follow up trial.

Bosulif, sponsored by Pfizer, was first approved in September 2012 in the U.S. for the treatment of adult patients with chronic, accelerated or blast phase Ph+ CML with resistance or intolerance to prior therapy.

The approval was based on results from BFORE (Bosutinib trial in first line chronic myelogenous leukemia treatment), a randomized multicenter, multinational, open-label phase III study which showed Bosulif 400 mg was associated with a significantly higher rate of patients achieving major molecular response at 12 months (47.2%; 95% CI, 40.9-53.4) compared to the rate achieved in patients treated with imatinib 400 mg (36.9%; 95% CI, 30.8-43.0), a current standard of care (two-sided P=0.0200).

Complete cytogenic response rate by 12 months was 77.2% (95% CI: 72.0, 82.5) for patients treated with Bosulif compared to 66.4% (95% CI: 60.4, 72.4) for patients treated with imatinib (two-sided P=0.0075).

Pfizer and Avillion entered into an exclusive collaborative development agreement in 2014 to conduct the BFORE trial. Under the terms of the agreement, Avillion provided funding and conducted the trial to generate the clinical data used to support this application and other potential regulatory filings for marketing authorization for Bosulif as first-line treatment for patients with chronic phase Ph+ CML. With this approval, Avillion is eligible to receive milestone payments from Pfizer. Pfizer retains all rights to commercialize Bosulif globally.

Bosulif (bosutinib) is an oral, once-daily, tyrosine kinase inhibitor, which inhibits the Bcr-Abl kinase that promotes CML; it is also an inhibitor of Src-family kinases.

In the U.S., Bosulif (bosutinib) is now indicated for the treatment of patients with newly-diagnosed chronic phase Philadelphiachromosome-positive chronic myelogenous leukemia and for the treatment of adult patients with chronic, accelerated or blast phase Ph+ CML with resistance or intolerance to prior therapy (first approved in September 2012).

A 400 mg tablet was also recently approved by the FDA in addition to the previously approved 100 mg and 500 mg strengths. The recommended dose for newly-diagnosed patients is 400 mg orally once daily with food. For patients who are resistant or intolerant to prior tyrosine kinase inhibitor therapy, the recommended dose is 500 mg orally once daily with food.

In Europe, Bosulif was granted conditional marketing authorization in March 2013 for the treatment of adult patients with Ph+ CML previously treated with one or more TKIs and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options. The European Medicines Agency (EMA) has also validated for review a Type II Variation application for use of Bosulif in the same patient population.

BFORE is a randomized, multicenter, open-label phase III study designed to assess the effectiveness and safety of Bosulif (bosutinib) as a first-line treatment for patients with chronic phase Ph+ CML.

The study enrolled 536 patients at multiple sites in North America, Asia and Europe. Patients were randomized 1:1 to receive Bosulif 400 mg or imatinib 400 mg, a standard of care, for the duration of the study.

The primary outcome was to show superiority of Bosulif over imatinib at 12 months by comparing MMR, or the proportion of patients in each arm whose levels of the Bcr-Abl1 kinase have dropped below 0.1%.


FDA approves Xgeva for prevention of skeletal-related events in multiple myeloma

Amgen said FDA has approved the supplemental Biologics License Application for Xgeva (denosumab) to expand the currently approved indication for the prevention of skeletal-related events in patients with bone metastases from solid tumors to include patients with multiple myeloma.

The approval is based on data from the pivotal phase III ‘482 study, which enrolled 1,718 patients.

“Up to 40 percent of patients remain untreated for the prevention of bone complications, and the percentage is highest among patients with renal impairment at the time of diagnosis,” said Noopur Raje, director of the Center for Multiple Myeloma at Massachusetts General Hospital Cancer Center. “Denosumab, which is not cleared through the kidneys, offers multiple myeloma patients bone protection with a convenient subcutaneous administration, providing patients with a novel treatment option.”

Xgeva is a fully human monoclonal antibody that binds to and neutralizes RANK ligand—a protein essential for the formation, function and survival of osteoclasts, which break down bone—thereby inhibiting osteoclast-mediated bone destruction.

The ‘482 study was an international, phase III, randomized, double-blind, multicenter trial of Xgeva compared with zoledronic acid for the prevention of skeletal-related events in adult patients with newly diagnosed multiple myeloma and bone disease.

In the study, a total of 1,718 patients (859 on each arm) were randomized to receive either subcutaneous Xgeva 120 mg and intravenous placebo every four weeks, or intravenous zoledronic acid 4 mg (adjusted for renal function) and subcutaneous placebo every four weeks.

The primary endpoint of the study was non-inferiority of Xgeva versus zoledronic acid with respect to time to first on-study skeletal-related event (pathologic fracture, radiation to bone, surgery to bone or spinal cord compression). Secondary endpoints included superiority of Xgeva versus zoledronic acid with respect to time to first on-study skeletal-related event and first-and-subsequent on-study skeletal-related event and evaluation of overall survival. Progression-free survival was an exploratory endpoint. The safety and tolerability of Xgeva were also compared with zoledronic acid.

The study met the primary endpoint, demonstrating non-inferiority of Xgeva to zoledronic acid in delaying the time to first on-study skeletal-related event in patients with multiple myeloma (HR=0.98, 95 percent CI: 0.85, 1.14; p=0.01). The secondary endpoints, delaying time to first skeletal-related event and delaying time to first-and-subsequent skeletal-related events, did not demonstrate superiority.

Overall survival was comparable between Xgeva and zoledronic acid, with a hazard ratio of 0.90 (95 percent CI: 0.70, 1.16; p=0.41). The median difference in progression-free survival favored Xgeva by 10.7 months (HR=0.82, 95 percent CI: 0.68-0.99; descriptive p=0.036). Median progression-free survival was 46.1 months (95 percent CI: 34.3 months, not estimable [NE], n=219) for Xgeva and 35.4 months (95 percent CI: 30.2 months, NE, n=260) for zoledronic acid.

Adverse events observed in patients treated with Xgeva were generally consistent with the known safety profile of Xgeva. The most common adverse reactions (greater than or equal to 10 percent) were diarrhea (34 percent), nausea (32 percent), anemia (22 percent), back pain (21 percent), thrombocytopenia (19 percent), peripheral edema (17 percent), hypocalcemia (16 percent), upper respiratory tract infection (15 percent), rash (14 percent) and headache (11 percent).

The most common adverse reaction resulting in discontinuation of Xgeva (greater than or equal to 1.0 percent) was osteonecrosis of the jaw. In the primary treatment phase of the ‘482 study, ONJ was confirmed in 4.1 percent of patients in the Xgeva group (median exposure of 16 months; range: 1 – 50) and 2.8 percent of patients in the zoledronic acid group (median 15 months, range: 1 – 45 months).


Kisqali receives breakthrough designation for HR+/HER2- breast cancer

Kisqali (ribociclib) received FDA Breakthrough Therapy designation for initial endocrine-based treatment of pre- or perimenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative advanced or metastatic breast cancer in combination with tamoxifen or an aromatase inhibitor.

The drug is sponsored by Novartis.

The designation is based on positive results of the phase III MONALEESA-7 trial demonstrating Kisqali in combination with tamoxifen or an aromatase inhibitor as initial endocrine-based therapy significantly prolonged progression-free survival compared to endocrine therapy alone (median PFS 23.8 (95% CI: 19.2 months-not reached) vs. 13.0 months (95% CI: 11.0-16.4 months); HR=0.553; 95% CI: 0.441-0.694; p<0.0001).

A total of 672 women between ages 25 and 58 years were enrolled and randomized in the trial. All treatment combinations also included goserelin. Treatment benefit with Kisqali combination therapy was consistent compared to the overall population regardless of treatment with tamoxifen or aromatase inhibitor endocrine partners, and across predefined patient subgroups, the company said.

MONALEESA-7 was the first phase III trial entirely dedicated to evaluating a CDK4/6 inhibitor in premenopausal women with HR+/HER2- advanced breast cancer. The trial evaluated Kisqali in combination with oral endocrine therapies (tamoxifen or an aromatase inhibitor) and goserelin compared to oral endocrine therapy and goserelin in this patient population.

In subgroup analyses of median PFS by endocrine partner, Kisqali in combination with tamoxifen and goserelin demonstrated 22.1 months median PFS compared to 11.0 months for tamoxifen and goserelin alone; Kisqali in combination with an aromatase inhibitor and goserelin demonstrated 27.5 months median PFS compared to 13.8 months for an aromatase inhibitor and goserelin alone.


FDA accepts sBLA, grants priority review for Adcetris

FDA has accepted for filing a supplemental Biologics License Application for Adcetris (brentuximab vedotin) in combination with chemotherapy for the frontline treatment of patients with advanced classical Hodgkin lymphoma. The FDA granted Priority Review for the application, and the Prescription Drug User Fee Act target action date is May 1, 2018.

The submission of the supplemental BLA is based on positive results from a phase III clinical trial called ECHELON-1 that was designed to determine if Adcetris in combination with chemotherapy could extend modified progression-free survival in previously untreated advanced classical Hodgkin lymphoma patients.

Adcetris, sponsored by Seattle Genetics Inc., is an antibody-drug conjugate directed to CD30, a defining marker of classical Hodgkin lymphoma. Adcetris is being evaluated globally as the foundation of care for CD30-expressing lymphomas in more than 70 corporate- and investigator-sponsored clinical trials. Adcetris is currently not approved as a frontline therapy for Hodgkin lymphoma.

In October 2017, the FDA granted Adcetris Breakthrough Therapy Designation based on the ECHELON-1 study results. The FDA’s Breakthrough Therapy Designation is intended to expedite the development and review of promising drug candidates for serious or life-threatening conditions. It is based upon clinical evidence of substantial improvement over existing therapies in one or more clinically significant endpoints.

The ECHELON-1 study evaluated a combination of Adcetris plus Adriamycin, vinblastine, dacarbazine compared to a recognized standard of care chemotherapy regimen, ABVD (which includes bleomycin), in frontline advanced classical Hodgkin lymphoma.

The positive results from the phase III ECHELON-1 trial were featured in the Plenary Scientific Session of the 59th American Society of Hematology Annual Meeting with simultaneous publication in the New England Journal of Medicine in December 2017. Results from the ECHELON-1 trial in 1,334 Hodgkin lymphoma patients included:

  • The trial achieved its primary endpoint with the combination of Adcetris plus AVD resulting in a statistically significant improvement in modified PFS versus the control arm of ABVD as assessed by an Independent Review Facility (p-value=0.035). This corresponds to a 23 percent reduction in the risk of progression, death, or need for additional anticancer therapy. Per IRF assessment, the two-year modified PFS rate for patients in the Adcetris plus AVD arm was 82.1 percent compared to 77.2 percent in the control arm.

  • The investigator assessment of modified PFS also demonstrated a statistically significant advantage for Adcetris plus AVD versus the control arm of ABVD (p-value <0.01).

  • All secondary endpoints, including interim analysis of overall survival, trended in favor of the Adcetris plus AVD arm.

  • The safety profile of Adcetris plus AVD in the ECHELON-1 trial was generally consistent with that known for the single-agent components of the regimen.

ECHELON-1 is a randomized, open-label, phase 3 trial is investigating ECHELON-1  plus AVD versus ABVD as frontline therapy in patients with advanced classical Hodgkin lymphoma.

The primary endpoint is modified PFS per Independent Review Facility assessment using the Revised Response Criteria for Malignant Lymphoma. Secondary endpoints include overall survival, complete remission and safety.

The multi-center trial was conducted in North America, Europe, South America, Australia, Asia and Africa. The study enrolled 1,334 patients who had a histologically-confirmed diagnosis of stage III or IV classical Hodgkin lymphoma and had not been previously treated with systemic chemotherapy or radiotherapy. The ECHELON-1 trial was conducted under a Special Protocol Assessment agreement from the FDA and the trial also received EMA scientific advice.

ECHELON-1 is being evaluated broadly in more than 70 clinical trials, including three phase III studies: the completed ECHELON-1 trial in frontline classical Hodgkin lymphoma, the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.


FDA grants breakthrough designation for Avelumab in combination with Inlyta in RCC

FDA has granted Breakthrough Therapy Designation for Avelumab in combination with Inlyta (axitinib) for treatment-naïve patients with advanced renal cell carcinoma.

This is the second Breakthrough Therapy Designation granted to Avelumab, sponsored by Merck KGaA and Pfizer Inc.

The Breakthrough Therapy Designation is based on the preliminary evaluation of clinical data from JAVELIN Renal 100, a global phase Ib study assessing the safety and efficacy of avelumab in combination with Inlyta for the treatment of treatment-naïve patients with advanced RCC.

Updated results from this phase Ib study were presented at the 2017 American Society of Clinical Oncology Annual Meeting. The FDA previously granted avelumab Breakthrough Therapy Designation for the treatment of patients with metastatic Merkel cell carcinoma whose disease has progressed after at least one previous chemotherapy regimen.

The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and over 7,000 patients evaluated across more than 15 different tumor types.

This includes JAVELIN Renal 101, a randomized, phase III, open-label, multicenter trial investigating avelumab in combination with Inlyta versus sunitinib as a first-line treatment option for advanced RCC, which recently completed recruitment.

In addition to RCC, cancer studies in the JAVELIN program include non-small cell lung cancer, breast cancer, head and neck cancer, Hodgkin’s lymphoma, melanoma, mesothelioma, MCC, ovarian cancer, gastric/gastroesophageal junction cancer, and urothelial carcinoma.


FDA grants orphan drug designation to Aptose Biosciences for CG’806 in AML

FDA has granted orphan drug designation to CG’806, a highly potent pan-FLT3/pan-BTK inhibitor, for the treatment of patients with acute myeloid leukemia. 

AML cells utilize multiple forms of the FLT3 receptor tyrosine kinase and other pathways to promote rapid proliferation and to escape the inhibitory activities of many therapeutics. CG’806 is a highly potent inhibitor that simultaneously targets all known forms of FLT3 and other key oncogenic pathways that drive the proliferation of AML cancer cells, thereby providing CG’806 with a broad range of activity against AML and a strategy to delay mutational escape.

CG‘806, sponsored by Aptose Biosciences Inc., is an oral, first-in-class pan-FLT3/pan-BTK inhibitor. This small molecule demonstrates potent inhibition of all wild type and mutant forms of FLT3 tested (including internal tandem duplication and mutations of the receptor tyrosine kinase domain and gatekeeper region), suppresses multiple oncogenic pathways operative in AML, eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML.

Likewise, CG’806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinases operative in B cell malignancies, suggesting CG’806 may also be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.


FDA accepts regulatory submission for Tagrisso in 1st-line EGFR-mutated NSCLC

AstraZeneca said the FDA has accepted a supplemental New Drug Application for the use of Tagrisso (osimertinib), a third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor with clinical activity against central nervous system metastases, in the 1st-line treatment of patients with metastatic non-small cell lung cancer whose tumors have EGFR mutations (exon 19 deletions or exon 21 (L858R) substitution mutations).

The FDA has granted Tagrisso Priority Review status, and previously granted Breakthrough Therapy Designation for TAGRISSO in the 1st-line treatment of patients with metastatic EGFR mutation-positive NSCLC.

The submission acceptance is based on data from the phase III FLAURA trial, in which Tagrisso significantly improved progression-free survival (PFS) compared to current 1st-line EGFR-TKIs, erlotinib or gefitinib, in previously-untreated patients with locally advanced or metastatic EGFRm NSCLC.

On Sept. 28, 2017, the NCCN Clinical Practice Guidelines in Oncology were updated to include the use of Tagrisso in the 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC. The use of Tagrisso in this indication is not yet approved by FDA.

Tagrisso once-daily tablets are approved by the FDA for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after an EGFR TKI therapy.


FDA grants priority review for Apalutamide in non-metastatic castration-resistant prostate cancer

Janssen Biotech Inc. said FDA has granted priority review designation for the New Drug Application for apalutamide, an investigational, next-generation oral androgen receptor inhibitor for the treatment of men with non-metastatic castration-resistant prostate cancer. Currently, there are no FDA-approved treatments for patients with non-metastatic CRPC.

The Priority Review designation means FDA’s goal is to take action on an application within six months of receipt, compared to 10 months for Standard Review. The FDA has assigned a Prescription Drug User Fee Act target date of April 2018 to render a decision on the apalutamide application.

The NDA submission for apalutamide, which was completed on Oct. 10, 2017, was based on phase III data from the pivotal ARN-509-003 (SPARTAN) clinical trial, which assessed the safety and efficacy of apalutamide versus placebo in men with non-metastatic CRPC who have a rapidly rising prostate specific antigen despite receiving continuous androgen deprivation therapy.

The primary endpoint of this study was metastasis-free survival. MFS is the time from randomization to first evidence of confirmed metastasis, or time to death. The SPARTAN study results have been accepted for oral presentation at the ASCO Genitourinary Cancers Symposium Feb. 8, 2018, in San Francisco.

Apalutamide is an investigational, next-generation oral androgn receptor inhibitor that inhibits the action of androgen in prostate cancer cells, and prevents binding of androgen to the androgen receptor, and translocation of the androgen receptor to the nucleus of the cancer cell.


Janssen and Legend Biotech enter deal to develop CAR-T therapy

Janssen Biotech Inc., a Janssen Pharmaceutical Company of Johnson & Johnson, said that it has entered into a worldwide collaboration and license agreement with Legend Biotech USA Inc. and Legend Biotech Ireland Limited, subsidiaries of Genscript Biotech Corp., to develop, manufacture and commercialize a chimeric antigen receptor T-cell drug candidate, LCAR-B38M, which specifically targets the B-cell maturation antigen. LCAR-B38M is currently accepted for review by the China Food and Drug Administration and in the planning phase of clinical studies in the United States for multiple myeloma. 

LCAR-B38M is the first CAR-T therapy accepted for review by the CFDA. Under the agreement, Legend will grant Janssen a worldwide license to jointly develop and commercialize LCAR-B38M in multiple myeloma with the Legend team of experts. Janssen will record worldwide net trade sales, except for sales made in Greater China.

The companies have entered into a 50/50 percent cost-sharing/profit-split arrangement, except in Greater China, where Janssen and Legend have a 30/70 percent cost-sharing/profit-split arrangement. Janssen will make an upfront payment of $350 million and additional payments based upon the achievement of development, regulatory and sales milestones.

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