publication date: Jan. 8, 2021

Drugs & Targets

Tagrisso receives FDA approval as adjuvant therapy for NSCLC with EGFR mutations

FDA has approved Tagrisso (osimertinib) for adjuvant therapy after tumor resection in patients with non-small cell lung cancer whose tumors have epidermal growth factor receptor exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.

Tagrisso is sponsored by AstraZeneca Pharmaceuticals LP.

Efficacy was demonstrated in a randomized, double-blind, placebo-controlled trial (ADAURA, NCT02511106) in patients with EGFR exon 19 deletions or exon 21 L858R mutation-positive NSCLC who had complete tumor resection, with or without prior adjuvant chemotherapy.

Eligible patients with resectable tumors (stage IB – IIIA) were required to have predominantly non-squamous histology and EGFR exon 19 deletions or exon 21 L858R mutations identified prospectively from tumor tissue in a central laboratory by the cobas EGFR Mutation Test. A total of 682 patients were randomized (1:1) to receive osimertinib 80 mg orally once daily or placebo following recovery from surgery and standard adjuvant chemotherapy, if given.

The major efficacy outcome measure was disease-free survival in patients with stage II – IIIA NSCLC determined by investigator assessment. Median DFS was not reached (38.8, NE) in patients on the osimertinib arm compared with 19.6 months (16.6, 24.5) on the placebo arm (HR 0.17 95% CI: 0.12, 0.23; <0.0001). DFS in the overall study population was a secondary efficacy outcome measure; the median was not reached (NE, NE) in patients on the osimertinib arm compared with 27.5 months (22, 36) on the placebo arm (HR 0.20 95% CI: 0.15, 0.27; <0.0001).


Iclusig receives FDA sNDA approval for adult patients with resistant or intolerant chronic-phase CML

FDA has approved the supplemental New Drug Application for Iclusig (ponatinib) for adult patients with chronic-phase chronic myeloid leukemia with resistance or intolerance to at least two prior kinase inhibitors.

Iclusig is sponsored by Takeda Pharmaceutical Company Ltd.

The updated label includes an optimized, response-based ICLUSIG dosing regimen in CP-CML with a daily starting dose of 45 mg and, upon achieving ≤1% BCR-ABL1IS, dose reduction to 15 mg. This dosing regimen aims to maximize benefit-risk by providing efficacy and decreasing the risk of adverse events, including arterial occlusive events.

The sNDA approval is based on data from the phase II OPTIC (Optimizing Ponatinib Treatment In CML) trial, as well as five-year data from the phase II PACE (Ponatinib Ph+ ALL and CML Evaluation) trial.

The OPTIC trial included patients with CP-CML whose disease was highly-resistant to their immediate prior TKI, the majority of whom (65%) did not achieve a response greater than complete hematological response on immediate prior therapy.

At 12 months, 42% of 88 patients utilizing the newly approved response-based dosing regimen (45 mg to 15 mg) achieved ≤1% BCR-ABL1IS, the primary endpoint of OPTIC, and at a median follow up time of 28.5 months, 73% of these patients maintained their response. In these patients, 13% experienced an AOE of any Grade, 7% experienced Grade 3 or higher. Risk factors such as uncontrolled hypertension or diabetes should be managed, and caution should be exercised when treating patients with active or substantial history of clinically significant, uncontrolled cardiovascular disease.


Xpovio receives FDA approval for refractory or relapsed multiple myeloma

FDA has approved Xpovio (selinexor) in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.

Xpovio is sponsored by Karyopharm Therapeutics Inc.

FDA granted Xpovio accelerated approval in 2019 in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

Efficacy of Xpovio in combination with bortezomib and dexamethasone was evaluated in the BOSTON Trial (KCP-330-023, NCT03110562), a randomized (1:1) open-label, multicenter, active comparator-controlled trial in patients with RRMM who had previously received at least one and at most three prior therapies.

Patients received once-weekly selinexor orally in combination with once-weekly bortezomib subcutaneous and low-dose dexamethasone twice-weekly orally compared to the standard twice-weekly bortezomib plus low-dose dexamethasone.

The main efficacy outcome measure was progression free survival assessed by an independent review committee using International Myeloma Working Group response criteria. The estimated median PFS was 13.9 months (95% CI: 11.7, Not Estimable) for the SVd arm and 9.5 months (95% CI: 7.6, 10.8) for the Vd arm (estimated hazard ratio 0.70; 95% CI: 0.53, 0.93).


Orgovyx receives FDA approval for advanced prostate cancer

FDA has approved the first oral gonadotropin-releasing hormone receptor antagonist, Orgovyx (relugolix) for adult patients with advanced prostate cancer.

Orgovyx is sponsored by Myovant Sciences inc.

Efficacy was evaluated in HERO (NCT03085095), a randomized, open label trial in men requiring at least one year of androgen deprivation therapy with either prostate cancer recurrence following radiation or surgery or newly diagnosed castration-sensitive advanced prostate cancer. Patients (N=934) were randomized (2:1) to receive relugolix 360 mg oral loading dose on the first day, followed by daily oral doses of 120 mg, or leuprolide acetate 22.5 mg injection subcutaneously every 3 months for 48 weeks.

The main efficacy outcome measure was medical castration rate defined as achieving and maintaining serum testosterone suppression to castrate levels (< 50 ng/dL) by day 29 through 48 weeks of treatment. The medical castration rate was 96.7% (95% CI: 94.9%, 97.9%) in the relugolix arm.

Margenza receives FDA approval for metastatic HER2-positive breast cancer

FDA has approved Margenza (margetuximab-cmkb) in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.

Margenza is sponsored by MacroGenics.

Efficacy was evaluated in SOPHIA (NCT02492711), a randomized, multicenter, open-label trial of 536 patients with IHC 3+ or ISH-amplified HER2+ metastatic breast cancer who had received prior treatment with other anti-HER2 therapies. Patients were randomized (1:1) to margetuximab plus chemotherapy or trastuzumab plus chemotherapy. Randomization was stratified by chemotherapy choice (capecitabine, eribulin, gemcitabine, or vinorelbine), number of lines of therapy in the metastatic setting (≤ 2, > 2), and number of metastatic sites (≤ 2, > 2).

The main efficacy outcome measures were progression-free survival by blinded independent central review and overall survival. Additional efficacy outcome measures were objective response rate and duration of response assessed by BICR.

Median PFS in the margetuximab arm was 5.8 months (95% CI: 5.5, 7.0) compared with 4.9 months (95% CI: 4.2, 5.6) in the control arm (HR 0.76; 95% CI: 0.59, 0.98; p=0.033). Confirmed ORR was 22% (95% CI: 17, 27) with a median DOR of 6.1 months (95% CI: 4.1, 9.1) in the margetuximab arm compared to an ORR of 16% (95% CI: 12, 20) and median DOR of 6.0 months (95%CI: 4.0, 6.9) in the control arm.


CPI-613 receives FDA Fast Track Designation for treatment of AML

FDA has granted Fast Track designation to CPI-613 (devimistat) for the treatment of acute myeloid leukemia.

CPI-613 is sponsored by Rafael Pharmaceuticals Inc.

Rafael Pharmaceuticals received Fast Track designation for devimistat for the treatment of metastatic pancreatic cancer in November 2020. The company also received Orphan Drug Designation for the treatment of soft tissue sarcoma for devimistat, and the initiation of a phase II clinical trial of devimistat in combination with hydroxychloroquine in patients with clear cell sarcoma of soft tissue.


EU CHMP issues positive opinion for Keytruda as first-line treatment in adult patients in colorectal cancer indication

The Committee for Medicinal Products for Human Use of the European Medicines Agency has adopted a positive opinion recommending approval of Keytruda, Merck’s anti-PD-1 therapy, as monotherapy for the first-line treatment of adult patients with metastatic microsatellite instability-high or mismatch repair deficient colorectal cancer.

Keytruda is sponsored by Merck.

This recommendation is based on results from the pivotal phase III KEYNOTE-177 trial, in which Keytruda, as a monotherapy, demonstrated a significant improvement in progression-free survival compared to chemotherapy (investigator’s choice: mFOLFOX6 with or without bevacizumab or cetuximab; or FOLFIRI with or without bevacizumab or cetuximab), a current standard of care.

Data from KEYNOTE-177 were presented at the virtual scientific program of the 2020 American Society of Clinical Oncology Annual Meeting and were published in The New England Journal of Medicine. The CHMP’s recommendation will now be reviewed by the European Commission for marketing authorization in the European Union, and a final decision is expected in the first quarter of 2021.Servier and Celsius Therapeutics collaborate on colorectal cancer research

Servier and Celsius Therapeutics have formed a strategic collaboration focused on the identification and validation of novel colorectal cancer drug targets.

“Through this collaboration, we will leverage Celsius’ single-cell genomics platform, machine learning capabilities, and target validation expertise to refine our understanding of the different subtypes of CRC and discover new drug targets with the goal of developing novel precision therapies for specific patient subsets,” Hugues Dolgos, global head of oncology research and development at Servier, said in a statement. “Servier will discover and develop candidate drugs leveraging our end-to-end small molecule and large molecule capabilities.”

Under the terms of collaboration, Celsius will analyze hundreds of samples from defined CRC patient populations using its proprietary single-cell genomics platform and will work to identify and validate new drug targets during the three-year research period. Servier will receive an exclusive option to research, develop, and commercialize products directed to up to three of the targets.

Celsius would receive an upfront payment and research funding, and would be eligible to receive over $700 million in potential discovery, development, and commercialization milestone payments, along with tiered royalties.


Bayer and Veracyte collaborate on precision oncology in thyroid cancer

Bayer and Veracyte have entered a collaboration to advance the Precision Oncology Patient Identification Program in thyroid cancer.

Through the program, Bayer will offer testing with Veracyte’s Afirma Xpression Atlas to identify underlying genomic drivers, including NTRK gene fusions, within patients’ tumors. The program will focus on patients with advanced or metastatic thyroid cancer that is radioactive iodine refractory who may potentially benefit from biomarker-driven therapies.

“Patients whose thyroid cancer contains actionable alterations and no longer responds to traditional radioactive iodine therapy now have targeted treatment options available to them. Our goal is to identify such patients so physicians can make more informed treatment decisions for their patients,” Bhavesh Ashar, senior vice president and head of U.S. Oncology at Bayer, said in a statement. “With its comprehensive ability to identify broad genomic alterations through its Afirma XA test and its widespread reach among physicians who diagnose thyroid cancer, Veracyte is an ideal collaborator for this program.”

The Afirma XA uses RNA whole-transcriptome sequencing to identify 905 DNA variants and 235 RNA fusions in 593 genes, including novel NTRK fusions, on fine needle aspirates taken from thyroid nodules or lymph nodes.

Through this collaboration, Bayer will provide Afirma XA testing at no cost to all eligible patients when ordered by the physician, regardless of the final results and treatment decision. Additionally, physicians of patients found to harbor NTRK gene fusions as an underlying driver in their thyroid cancer will be alerted of the results. The companies anticipate the program to launch in the first quarter of next year.


Servier to acquire Agios Pharmaceuticals’ oncology business

Servier has entered into an agreement for the acquisition of Agios Pharmaceuticals’ oncology business including its commercial, clinical and research-stage oncology portfolio for up to $2 billion, including an upfront payment of $1.8 Billion and a potential $200 million in regulatory milestone, plus royalties.

The transaction has been approved by both companies’ respective boards of directors. Subject to receipt of regulatory clearances and approval by Agios’ shareholders, the acquisition is expected to close in Q2 2021.

Servier has made oncology one of its strategic priorities, allocating 50% of its overall research and development budget to this therapeutic area. The acquisition will reinforce Servier’s presence in the U.S., where the group has been operating since 2018.

The transaction includes the transfer of Agios’ oncology portfolio and associated employees, including its marketed medicine Tibsovo, which is approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory acute myeloid leukemia and for adults with newly diagnosed IDH1-mutant AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy.

Tibsovo is also under investigation in two phase III combination trials in newly diagnosed AML, and as a potential treatment for previously treated IDH1-mutant cholangiocarcinoma and IDH1-mutant myelodysplastic syndrome. Servier will also acquire Agios’ co-commercialization responsibilities for Bristol Myers Squibb’s Idhifa (enasidenib) and conduct certain clinical development activities within the Idhifa development program.

In addition, the transaction includes Agios’ oncology pipeline and clinical programs, including vorasidenib, an investigational, brain-penetrant, dual inhibitor of mutant IDH1 and IDH2 which is currently being studied in the registration-enabling phase III INDIGO study in patients with IDH-mutant low-grade glioma; AG-270, an investigational first-in-class methionine adenosyltransferase 2a inhibitor being evaluated in combination with taxanes in patients with methylthioadenosine phosphorylase-deleted non-small cell lung cancer and pancreatic cancer; AG-636, a novel inhibitor of dihydroorotate dehydrogenase; and Agios’ oncology research programs.

All of Agios’ U.S.-based employees who primarily support the oncology business will receive a comparable offer at Servier.


Kite and Oxford BioTherapeutics establish cell therapy research collaboration in blood cancers and solid tumors

Kite, a Gilead Company, and Oxford BioTherapeutics Ltd. have entered into a research collaboration to evaluate five novel targets for a number of hematologic and solid tumor indications.

Through this collaboration, OBT will validate five novel oncology drug targets, previously identified using OBT’s OGAP discovery platform, and generate antibodies against these targets. Kite and Gilead will have the exclusive right to develop and commercialize therapies based on these targets or antibodies.

Under the terms of the agreement, OBT will receive an upfront payment and will be eligible to receive additional payments based on achievement of certain discovery, clinical and regulatory milestones, as well as royalties on future potential sales.

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