On October 27, 2023 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported the presentation of four posters that provide new-real world evidence indicating that trilaciclib administered prior to platinum-based chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC) lowers the rate of hospitalization and cytopenia events and may improve survival (Press release, G1 Therapeutics, OCT 27, 2023, View Source [SID1234636408]). In addition, multiple real-world analyses indicate the consistent impact of chemotherapy-induced myelosuppressive events, including severe neutropenia, thrombocytopenia, and anemia, on patients with ES-SCLC being treated with platinum-based chemotherapy as well as the resulting impact on healthcare resource utilization. The posters are being presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Quality Care Symposium, held October 27th and 28th in Boston, MA. A copy of the posters will be made available on the G1 Therapeutics website following the presentations here.

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"The burden of chemotherapy-induced myelosuppression not only puts patients at risk for serious adverse events but can also stress the healthcare system," said Raj Malik, M.D., Chief Medical Officer at G1 Therapeutics. "Findings from these real-world analyses demonstrate the need to protect patients from the harmful side effects of chemotherapy so that they can continue their treatment. Trilaciclib offers the potential to transform the treatment experience, and these new data underscore the results we’ve seen across multiple analyses showing the positive impact of proactive treatment with trilaciclib."

The poster presentations include:

Myelosuppression and Healthcare Utilization Among Patients with Chemotherapy-Treated Extensive-Stage Small Cell Lung Cancer (ES-SCLC) with and without Trilaciclib from Community Oncology Practices (Gajra, A. et al.)

This observational study compared cytopenia-related outcomes and HRU between patients with ES-SCLC who received trilaciclib prior to chemotherapy vs. those who did not in a real-world setting. Using the EMOL Health’s database, which includes >7 million patients from >500 U.S. community oncology practices, structured electronic medical records (EMRs) from January 2020 to April 2023 were examined for this study, supplemented by chart review. Descriptive analyses were performed for patient baseline characteristics and outcomes between the two matched cohorts. Adjusted analyses were conducted to evaluate grade ≥3 myelosuppression in ≥1, ≥2, and all three lineages, as well as all-cause hospitalization.

Results of this retrospective study suggest that patients receiving trilaciclib prior to chemotherapy (n=77) in cycles 1-4 had lower rates of grade ≥3 myelosuppressive HAEs and cytopenia-related HRU compared to the matched comparison cohort (n=77) not treated with trilaciclib:

11.2% of trilaciclib-treated patients had grade ≥3 HAEs in ≥1 lineage compared to 30.7% of patients in the comparison cohort.
1.2% of trilaciclib-treated patients had grade ≥3 HAEs in ≥2 lineages compared to 13.5% of patients in the comparison cohort.
0.4% of trilaciclib-treated patients had grade ≥3 HAEs in 3 lineages compared to 4.9% of patients in the comparison cohort.
G-CSF administered any time during the cycle was reduced by 60.7% in patients receiving trilaciclib compared to those not receiving trilaciclib in the comparison cohort (25.6% vs. 65.2%). Similarly, RBC transfusions and erythropoiesis-stimulating agent (ESA) use were reduced by 84.4% (1.7% vs. 10.9%) and 42.2% (3.7% vs. 6.4%), respectively, in patients receiving trilaciclib compared to those that did not.

After adjusting for age, sex, index line of therapy, and number of chemotherapy cycles receiving trilaciclib, the odds of developing an event of grade ≥3 myelosuppression in ≥1, ≥2, and 3 lineages were reduced by 70%, 90%, and 96%, respectively, with trilaciclib use. All results were statistically significant. The odds of all-cause hospitalization were reduced by 51% with trilaciclib use, though not statistically significant.

Assessment of Hospitalizations and Cytopenia Events Among Patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) Receiving Chemotherapy with Trilaciclib (Huang, H. et al.)

The goal of this study was to evaluate real-world rates of hospitalizations and cytopenia-related outcomes in patients with ES-SCLC treated with chemotherapy and trilaciclib, compared to patients who did not receive trilaciclib. This retrospective study used data from the 100% Medicare Fee-for-Service and the Inovalon MORE2 closed claims databases between February 2020 and September 2023. Included in the study were 132 patients who received trilaciclib prior to chemotherapy (and did not receive prophylactic G-CSF) and 11,940 patients who did not receive trilaciclib.

Hospitalization Outcomes

Patients receiving trilaciclib had a lower rate of all-cause per patient per month (PPPM) hospitalizations during follow-up (0.14±0.25 vs. 0.19±0.27; p<0.01) and were less likely to be hospitalized within 90 days post-chemotherapy initiation (21.2% vs. 32.1%; p<0.01), compared to the patients who did not receive trilaciclib.
Cytopenia Related Outcomes

Compared to patients who did not receive trilaciclib, patients receiving trilaciclib prior to their chemotherapy had a statistically significantly lower risk of febrile neutropenia (relative risk 15.5%, p=0.03) and numerically lower risk of anemia, neutropenia and thrombocytopenia in the 90-day post-index period.
Survival Outcomes

Patients receiving trilaciclib had a numerically higher rate of survival at six months (84.1%) compared to the non-trilaciclib group (72.3%) and a survival hazard ratio of 0.63 (95% CI: 0.35-1.14, p=0.13) compared to patients not receiving trilaciclib.
This real-world study suggests that trilaciclib administered prior to chemotherapy was associated with lower rates of hospitalizations and cytopenia events, along with an early trend toward improved survival. Trilaciclib is an effective proactive intervention to prevent adverse events associated with treatment for ES-SCLC.

Burden of Myelosuppression in Extensive-Stage Small-Cell Lung Cancer Patients Receiving Chemotherapy: Retrospective Analysis of Real-World Data from Tennessee Oncology (Blakely, L.J. et al.)

Using data from Tennessee Oncology (TNO), one of the largest community-based cancer care specialists in the U.S., this study evaluated the burden of myelosuppression as assessed by hematologic adverse events (HAEs), including anemia, neutropenia, and thrombocytopenia among patients with ES-SCLC treated with chemotherapy (no trilaciclib). Additionally, it assessed cytopenia-related and all-cause healthcare resource use (HRU) among the same population.

The retrospective analysis followed 152 ES-SCLC patients who received chemotherapy (with or without immunotherapy) but did not receive trilaciclib at any point in their therapy. Among these patients, the prevalence of single and multi-lineage myelosuppression during follow up period (10 month average follow-up period after initiation of chemotherapy) was as follows:

63.8% had grade ≥ 3 myelosuppressive HAE in ≥ 1 lineage.
49.3% had grade ≥ 3 neutropenia, 29.0% had grade 3 anemia, and 28.3% had grade ≥ 3 thrombocytopenia.
32.2% had grade ≥3 HAEs in ≥2 lineages.
10.5% had grade ≥3 HAEs in 3 lineages.
Cytopenia-related and all-cause healthcare resource use (HRU) during follow up period included:

76.3% of patients received granulocyte colony-stimulating factor (G-CSF) administration at any time during follow-up.
30.3% received a red blood cell (RBC) transfusion.
57.9% experienced at least one inpatient admission.
67.8% experienced at least one emergency room visit.
100% experienced at least one outpatient visit.
These results suggest that, consistent with other published studies, there is high patient burden associated with traditional management of myelosuppression in patients with ES-SCLC in a community oncology practice like TNO, indicating an unmet need in this population. Therapies that protect bone marrow from myelosuppression have potential to reduce such burden.

Patient Characteristics Associated with Myelosuppression Among Patients with Extensive-Stage Small Cell Lung Cancer Treated with Chemotherapy in The Community Oncology Setting (Goldschmidt, J. et al.)

This retrospective observational study examined the association between patient attributes and the risk of chemotherapy-induced myelosuppression in patients with ES-SCLC, utilizing real-world data from the U.S. Oncology Network’s iKnowMed (iKM) electronic health record system.

This study found that all patients with ES-SCLC are at a similar risk of myelosuppressive events, irrespective of patient characteristics (age, sex, race, ECOG performance status) and baseline lab values (hemoglobin, ANC, or platelet count), which were not found to be risk factors for myelosuppressive events for ES-SCLC patients receiving chemotherapy. Chemotherapy intensity and prophylactic management had a more prominent role in risk of myelosuppression. Additionally, the study found that treatment delays and holds are associated with a higher risk of myelosuppressive events. These findings suggest that how patients present in their initial visits are not necessarily predictive of myelosuppressive events.

About Small Cell Lung Cancer
In the United States, approximately 30,000 small cell lung cancer patients are treated annually. SCLC, one of the two main types of lung cancer, accounts for approximately 14% of all lung cancers. SCLC is an aggressive disease and tends to grow and spread faster than NSCLC. It is usually asymptomatic; once symptoms do appear, it often indicates that the cancer has spread to other parts of the body. About 70% of people with SCLC will have cancer that has metastasized at the time they are diagnosed. The severity of symptoms usually increases with increased cancer growth and spread. From the time of diagnosis, the general 5-year survival rate for people with SCLC is 6%. The five-year survival rates for limited-stage (the cancer is confined to one side of the chest) SCLC is 12% to 15%, and for extensive stage (cancer has spread to the other lung and beyond), survival rates are less than 2%. Chemotherapy is the most common treatment for ES-SCLC.

On October 27, 2023 Coherus BioSciences, Inc. ("Coherus", NASDAQ: CHRS), and Shanghai Junshi Biosciences Co., Ltd. (Junshi Biosciences, HKEX: 1877; SSE: 688180) reported that the U.S. Food and Drug Administration (FDA) approved LOQTORZI (toripalimab-tpzi) in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced NPC, and as monotherapy for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy (Press release, Coherus Biosciences, OCT 27, 2023, View Source [SID1234636407]). The approval was based on results of the JUPITER-02 Phase 3 study and the POLARIS-02 Phase 2 study and is irrespective of a patient’s PD-L1 status. LOQTORZI is a next-generation, programmed death receptor-1 (PD-1) monoclonal antibody that blocks PD-1 ligands PD-L1 and PD-L2 with high potency at a unique site on the PD-1 receptor, enabling the immune system to activate and kill the tumor.

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In the JUPITER-02 Phase 3 study, LOQTORZI combined with chemotherapy significantly improved progression-free survival (PFS), reducing the risk of disease progression or death by 48% compared to chemotherapy alone. LOQTORZI also demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), with treatment resulting in a 37% reduction in the risk of death versus chemotherapy alone.

The safety profile of LOQTORZI was consistent with the PD-1 inhibitor class. The incidence of Grade ≥3 adverse events (AEs) (89.7% vs 90.2%) and fatal AEs (3.4% vs 2.8%) was similar between the two arms. AEs leading to discontinuation of LOQTORZI versus placebo (11.6% vs 4.9%), immune-related adverse events (irAEs) (54.1% vs. 21.7%), and Grade ≥3 irAEs (9.6% vs. 1.4%) were more frequent in the LOQTORZI arm.

In the POLARIS-02 clinical study LOQTORZI demonstrated durable antitumor activity in patients with recurrent or metastatic NPC who failed previous chemotherapy, with an objective response rate (ORR) of 20.5%, a disease control rate (DCR) of 40.0%, and a median OS of 17.4 months with an acceptable safety profile.

NPC is an aggressive cancer that starts in the nasopharynx, the upper part of the throat behind the nose and near the base of skull. Due to the location of the primary tumor, surgery is rarely an option, and patients with localized disease are treated primarily with radiation and chemotherapy. LOQTORZI is the first FDA-approved agent for NPC patients.

"LOQTORZI’s first approval is a pivotal event for Coherus as an innovative oncology company. As a next generation PD-1 inhibitor it is the keystone of our I-O strategy to extend cancer patient survival as shown with the impressive results in NPC," said Denny Lanfear, Chairman and Chief Executive Officer of Coherus. "We are particularly excited to now turn our attention to developing LOQTORZI across multiple tumor types in combination with I-O agents that target the tumor microenvironment, such as our IL27-targeted antibody, casdozokitug, and our CCR8 inhibitor CHS-114, potentially greatly expanding the number of cancer patients achieving improved survival benefit."

"Today’s FDA approval of LOQTORZI is very encouraging for those living with NPC who currently have very limited treatment options and are in need of new therapies to treat this aggressive and life-threatening form of cancer," said Jong Chul Park, M.D., Assistant Professor, Harvard Medical School and attending physician at the Center for Head and Neck Cancers at Massachusetts General Hospital Cancer Center. "LOQTORZI is a new treatment option that has demonstrated the ability to significantly improve PFS and OS and should quickly emerge as the new standard of care when used in combination with chemotherapy."

The recommended LOQTORZI dose with cisplatin and gemcitabine is 240 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months. The recommended LOQTORZI dose as a single agent for previously treated NPC is 3 mg/kg every two weeks until disease progression or unacceptable toxicity.

LOQTORZI is expected to be available in the United States in Q1 2024.

"The impressive results from JUPITER-02 and POLARIS-02 have provided conclusive evidence that establishes toripalimab, in combination with chemotherapy or as monotherapy, as the standard therapy for advanced NPC," said Professor Ruihua Xu of Sun Yat-sen University Cancer Center, the principal investigator of JUPITER-02 and POLARIS-02. "This great achievement was only made possible through the solid foundation laid by countless oncology experts over decades of in-depth research, as well as the selfless dedication of the patients and research teams involved in our toripalimab studies. We hope that this promising therapy will close the treatment gap for international NPC patients struggling to find effective therapies, bringing them renewed hope for better survival."

"We’re excited to reach another significant company milestone of ‘going overseas’," said Dr. Ning LI, Chief Executive Officer of Junshi Biosciences. "Following etesevimab, toripalimab has become Junshi Biosciences’ second product to receive FDA approval for commercialization—an achievement that will further enhance the company’s international presence. Currently, the establishment of toripalimab’s global commercialization network is in progress, and the network aims to span over 50 countries. In accordance with the company’s ‘In China, For Global’ strategy, we will continue working with our collaborators to promote the commercialization of toripalimab in other regions, in order to provide innovative and high-quality drugs from China to more patients overseas."

About JUPITER-02
JUPITER-02 is the largest randomized, double-blind, placebo-controlled, international, multi-center Phase 3 clinical study to evaluate a checkpoint inhibitor plus chemotherapy for the first-line treatment of recurrent or metastatic NPC.

Two hundred eighty-nine patients with advanced NPC who had received no prior chemotherapy for recurrent/metastatic disease were randomized 1:1 to receive LOQTORZI (toripalimab-tzpi) 240 mg or placebo in combination with gemcitabine 1000 mg/m2 (days 1 and 8) and cisplatin 80 mg/m2 (day 1) of every three-week treatment cycle, followed by toripalimab-tzpi or placebo monotherapy every 3 weeks until disease progression, intolerable toxicity, or completion of two years of treatment. JUPITER-02 included all eligible patients regardless of PD-L1 status and histologies.

In this study, LOQTORZI met the primary endpoint, demonstrating a significant improvement in PFS (assessed by a Blinded Independent Review Committee (BIRC)) compared to the chemotherapy alone arm with toripalimab-tzpi, reducing the risk of disease progression or death by 48% (HR=0.52 [95% CI: 0.36, 0.74; P<0.0003). Improvement in PFS was observed irrespective of PD-L1 status.

LOQTORZI demonstrated a statistically significant and clinically meaningful improvement in OS with treatment resulting in a 37% reduction in the risk of death versus chemotherapy alone. Median OS has not been reached in the LOQTORZI arm versus 33.7 months for chemotherapy treatment alone (HR=0.63 [95% CI 0.45-0.89]; P=0.0083).

LOQTORZI also demonstrated an improvement in ORR, duration of response (DoR), and DCR. In the study, 77% of patients treated with LOQTORZI experienced a complete or partial response (19% and 58% respectively) and the median duration of response was 10 months in the LOQTORZI arm versus 5.7 months in the chemotherapy alone arm.

About LOQTORZI Solutions
Coherus is committed to supporting patients with programs for zero out-of-pocket costs or patient assistance for eligible patients so that they may benefit from a proven PD-1 immunotherapy, with less financial burden.
Our robust patient support services include:

Reimbursement support
Patient support
Access support
Commitment to the NPC community
Given the limited resources available to patients and caregivers contending with NPC, Coherus has launched a new educational community resource, NPCFacts.com, which includes detailed information about the types of NPC as well as its causes, diagnosis, and treatment options.
In addition to education about nasopharyngeal carcinoma, the website includes links to patient-advocacy organizations providing additional resources, including the Head and Neck Cancer Alliance, Support for People with Oral Head and Neck Cancer, and Thyroid Head and Neck Cancer Foundation.
The website includes a companion website for healthcare professionals treating patients with NPC, including educational resources and opportunities for peer-to-peer education.

About NPC
NPC is a type of aggressive cancer that starts in the nasopharynx, the upper part of the throat behind the nose and near the base of the skull. NPC is rare in the United States, with an annual incidence of fewer than one per 100,000. The five-year survival rate for all patients diagnosed with NPC is approximately 60%, however, those who are diagnosed with advanced disease have a five-year survival rate of approximately 49%.

Due to the location of the primary tumor, surgery is rarely an option, and patients with localized disease are treated primarily with radiation and chemotherapy. Patients treated with chemotherapy alone experience poor prognosis: only 20% experience one-year PFS; up to 50% developed distant metastasis during their disease course; and low median OS of 29 months.

LOQTORZI is the first FDA-approved therapy for NPC and will represent a new standard of care for treating the disease when used in combination with cisplatin and gemcitabine in the first line setting or as monotherapy in the second line or greater setting.

About LOQTORZI (toripalimab-tpzi)
LOQTORZI is a next generation anti-PD-1 monoclonal antibody that blocks PD-L1 binding to the PD⁠-⁠1 receptor at a unique site with high affinity and activates antitumor immunity demonstrating improvement in the overall survival of cancer patients in several tumor types.

INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS

LOQTORZI (toripalimab-tpzi) is indicated:

In combination with cisplatin and gemcitabine, for the first-line treatment of adults with metastatic or with recurrent, locally advanced nasopharyngeal carcinoma (NPC).
As a single agent, for the treatment of adults with recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy.
IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions
Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions. Immune-mediated adverse reactions, which can be severe or fatal, occur in any organ system or tissue, affect more than one body system simultaneously, and occur at any time after starting PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment, they can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies.

Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue LOQTORZI based on severity and type of reaction (see Dosage and Administration in Prescribing Information). In general, If LOQTORZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
LOQTORZI can cause immune-mediated pneumonitis.

In patients receiving LOQTORZI in combination with cisplatin and gemcitabine, immune-mediated pneumonitis occurred in 2.1% (3/146) of patients, including Grade 2 (1.4%) adverse reactions. Pneumonitis resolved in 67% (2/3) of these patients.
In patients receiving LOQTORZI monotherapy, immune-mediated pneumonitis occurred in 2.6% (22/851) of patients, including fatal (0.2%), Grade 3 (0.7%), and Grade 2 (1.1%) adverse reactions. Systemic corticosteroids were required in 82% (18/22) of patients with pneumonitis. Pneumonitis led to permanent discontinuation of LOQTORZI in 1.2% (10/851) of patients. Pneumonitis resolved in 23% (5/22) of these patients.
Immune-Mediated Colitis
LOQTORZI can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving LOQTORZI monotherapy, immune-mediated colitis occurred in 0.4% (3/851) of patients, including Grade 3 (0.2%) and Grade 2 (0.1%) adverse reactions. Colitis resolved in all 3 patients.

Hepatotoxicity and Immune-Mediated Hepatitis
LOQTORZI can cause immune-mediated hepatitis.

In patients receiving LOQTORZI in combination with cisplatin and gemcitabine, immune-mediated hepatitis occurred in 0.7% (1/146) of patients, which was a Grade 3 (0.7%) adverse reaction. The patient with immune-mediated hepatitis required systemic corticosteroids.
In patients receiving LOQTORZI monotherapy, immune-mediated hepatitis occurred in 3.3% (28/851) of patients, including Grade 4 (0.8%), Grade 3 (2.1%), and Grade 2 (0.4%) adverse reactions. Hepatitis led to permanent discontinuation of LOQTORZI in 1.1% of patients and withholding of LOQTORZI in 0.8% of patients. Hepatitis resolved in 54% (15/28) of these patients.
Immune-Mediated Endocrinopathies
Adrenal Insufficiency
LOQTORZI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold or permanently discontinue LOQTORZI depending on severity. In patients receiving LOQTORZI monotherapy, adrenal insufficiency occurred in 0.5% (4/851) of patients, including Grade 2 (0.4%) and Grade 1 (0.1%) adverse reactions. Systemic corticosteroids were required in 75% (3/4) of the patients with adrenal insufficiency. Adrenal insufficiency led to withholding of LOQTORZI in 0.1% (1/851) of patients. In the one patient in whom LOQTORZI was withheld, LOQTORZI was reinitiated after symptom improvement.

Hypophysitis
LOQTORZI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effects such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue LOQTORZI depending on severity. In patients receiving LOQTORZI monotherapy, hypophysitis occurred in 0.4% (3/851) of patients receiving LOQTORZI, including Grade 3 (0.2%) and Grade 2 (0.1%) adverse reactions. All three patients received systemic corticosteroids. Hypophysitis led to permanent discontinuation of LOQTORZI in 0.1% (1/851) of patients and withholding of LOQTORZI in 0.1% (1/851) of patients. The one patient in whom LOQTORZI was withheld reinitiated LOQTORZI.

Thyroid Disorders
LOQTORZI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue LOQTORZI depending on severity.

In patients receiving LOQTORZI in combination with cisplatin and gemcitabine, thyroiditis occurred in 2.1% (3/146) of patients receiving LOQTORZI, including Grade 2 (1.4%). Three patients required thyroid hormone replacement therapy. Thyroiditis resolved in one of the 3 patients. Hyperthyroidism occurred in 1.4% (2/146) of patients receiving LOQTORZI in combination with cisplatin and gemcitabine. Hyperthyroidism resolved in these 2 patients. Hypothyroidism occurred in 30% (44/146) of patients receiving LOQTORZI in combination with cisplatin and gemcitabine, including Grade 2 (24%) and Grade 1 (6%). Eighty percent of the 44 patients required thyroid hormone replacement therapy. LOQTORZI was withheld in 2.1% (3/146) of the patients. Of the 3 patients in whom LOQTORZI was withheld, 2 patients reinitiated LOQTORZI.
In patients receiving LOQTORZI monotherapy, thyroiditis occurred in 0.6% (5/851) patients receiving LOQTORZI, including Grade 2 (0.1%). Two of these 5 patients received systemic corticosteroids and 2 required thyroid hormone replacement therapy. Thyroiditis resolved in 2 of the 5 patients. Hyperthyroidism occurred in 7% (55/851) of patients receiving LOQTORZI, including Grade 2 (1.9%). Hyperthyroidism resolved in 85% (47/55) of the patients. Hypothyroidism occurred in 15% (128/851) of patients receiving LOQTORZI, including Grade 2 (8%). Sixty three percent of the 128 patients required thyroid hormone replacement therapy. LOQTORZI was withheld in 0.5% of patients. Of the 4 patients in whom LOQTORZI was withheld, 3 patients reinitiated LOQTORZI.
Type 1 Diabetes Mellitus, which can present with Diabetic Ketoacidosis
Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue LOQTORZI depending on severity. In patients receiving LOQTORZI monotherapy, diabetes mellitus occurred in 0.9% (8/851) of patients receiving LOQTORZI, including Grade 4 (0.1%), Grade 3 (0.7%), and Grade 2 (0.1%). Diabetes mellitus led to permanent discontinuation in 0.4% of patients. Six of the 8 (75%) patients with diabetes mellitus required long-term insulin therapy.

Immune-Mediated Nephritis with Renal Dysfunction
LOQTORZI can cause immune-mediated nephritis.

In patients receiving LOQTORZI in combination with cisplatin and gemcitabine, immune-mediated nephritis occurred in 0.7% (1/146) of patients receiving LOQTORZI. The one patient with immune-mediated nephritis (Grade 4) required systemic corticosteroids and nephritis led to discontinuation of LOQTORZI. Nephritis resolved in this patient.
In patients receiving LOQTORZI monotherapy, immune-mediated nephritis occurred in 0.5% (4/851) of patients, including Grade 3 (0.5%) adverse reactions. Nephritis resolved in 75% (3/4) of these patients.
Immune-Mediated Dermatologic Adverse Reactions
LOQTORZI can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue LOQTORZI depending on severity.

In patients receiving LOQTORZI in combination with cisplatin and gemcitabine, immune-mediated dermatologic adverse reactions occurred in 8% (12/146) of patients, including Grade 3 (3.4%) and Grade 2 (1.4%) adverse reactions. Systemic corticosteroids were required in 25% (3/12) of the patients with immune-mediated dermatologic adverse reactions. Immune-mediated dermatologic adverse reactions led to permanent discontinuation of LOQTORZI in 2.1% (3) of patients. Immune-mediated dermatologic adverse reactions resolved in 92% (11/12) of these patients.
In patients receiving LOQTORZI monotherapy, immune-mediated dermatologic adverse reactions occurred in 4% (34/851) of patients, including Grade 3 (0.4%) and Grade 2 (1.4%) adverse reactions. Immune-mediated dermatologic adverse reactions led to withholding of LOQTORZI in 0.4% (3) of the patients. Systemic corticosteroids were required in 12% (4/34) of the patients with immune-mediated dermatologic adverse reactions. Immune-mediated dermatologic adverse reactions resolved in 71% (24/34) of these patients.
Other Immune-Mediated Adverse Reactions
The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received LOQTORZI or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions.

Cardiac/Vascular: Myocarditis, pericarditis, vasculitis, pericardial effusion
Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy
Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis
Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis, polymyalgia rheumatica, dermatomyositis
Endocrine: Hypoparathyroidism
Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection
Infusion-Related Reactions
LOQTORZI can cause severe or life-threatening infusion-related reactions including hypersensitivity and anaphylaxis.

In patients receiving LOQTORZI in combination with cisplatin and gemcitabine, infusion-related reactions have been reported in 4.1% of patients, including Grade 2 (0.7%) reactions.
In patients receiving LOQTORZI monotherapy, infusion-related reactions occurred in 2% of 851 patients, including Grade 3 (0.1%) and Grade 2 (0.6%). LOQTORZI was withheld for one Grade 3 infusion related reaction. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. Interrupt or slow the rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions. For severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions, stop infusion and permanently discontinue LOQTORZI.
Complications of Allogeneic Hematopoietic Stem Cell Transplant (HSCT)
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity
LOQTORZI can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LOQTORZI and for 4 months after the last dose.

Lactation
There are no data on the presence of toripalimab-tpzi in human milk; its effects on the breastfed child, or on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to toripalimab-tpzi are unknown. Because of the potential for serious adverse reactions in breastfed children, advise lactating women not to breastfeed during treatment with LOQTORZI and for 4 months after the last dose.

Serious Adverse Reactions

In JUPITER-02, when LOQTORZI was administered in combination with cisplatin and gemcitabine for the first-line treatment of recurrent, locally advanced or metastatic nasopharyngeal carcinoma, serious adverse reactions occurred in 43% of patients. Serious adverse drug reactions in ≥2% were thrombocytopenia (14%), neutrophil count decreased (10%), pneumonia (10%), anemia (9%), abnormal hepatic function (2.7%), and rash (2.1%). There were three fatal adverse reactions (2.1%): one due to epistaxis; one due to intracranial hemorrhage associated with immune-related thrombocytopenia and coagulopathy; and one due to pneumonia. Permanent discontinuation of LOQTORZI, due to an adverse reaction occurred in 12% of patients. Adverse reactions resulting in permanent discontinuation of LOQTORZI in ≥1% were pneumonia (2.1%), pulmonary tuberculosis (1.4%), rash (1.4%), and vomiting (1.4%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased neutrophils (58%), decreased lymphocytes (57%), decreased hemoglobin (50%) decreased platelets (33%), decreased potassium (10%), decreased sodium (9%), increased alanine aminotransferase (6%), increased or decreased magnesium (4.2% each), decreased calcium (3.5%), increased aspartate aminotransferase (2.7%), increased bilirubin (2.1%).
In POLARIS-02, when LOQTORZI was administered as a single agent to patients with previously treated, unresectable or metastatic nasopharyngeal carcinoma, serious adverse reactions occurred in 24% of patients. Serious adverse drug reactions in ≥2% were pneumonia (4.7%), abnormal hepatic function (2.6%), and hyperbilirubinemia (2.1%). Fatal adverse reactions occurred in 3.7% of patients who received LOQTORZI, including death not otherwise specified (1.6%), tumor hemorrhage (0.5%), hepatic failure and thrombocytopenia (0.5%), hyponatremia (0.5%), and sudden death (0.5%). Permanent discontinuation of LOQTORZI due to an adverse reaction occurred in 9% of patients. Adverse reaction resulting in permanent discontinuation of LOQTORZI in ≥1% included pneumonia (1.1%), abnormal hepatic function (1.1%), and hyperbilirubinemia (1.1%). The most common Grade 3 or 4 laboratory abnormalities (≥2%), were decreased sodium (11%), decreased lymphocytes (9%), decreased hemoglobin (6%), increased aspartate aminotransferase (3.8%), decreased phosphate (3.2%), and increased alkaline phosphatase (2.2%).
Common Adverse Reactions

In JUPITER-02, the most common adverse reactions (≥20%) were nausea (71%), vomiting (68%), decreased appetite (55%), constipation (39%), hypothyroidism (38%), rash (36%), pyrexia (32%), diarrhea (31%), peripheral neuropathy (30%), cough (26%), musculoskeletal pain (25%), upper respiratory infection (23%), insomnia (23%), dizziness (21%), and malaise (21%).
In POLARIS-02, in patients with previously treated, unresectable or metastatic nasopharyngeal carcinoma, the most common (≥20%) adverse reactions were hypothyroidism (27%), fatigue (22%), and cough (20%).
Please see Prescribing Information for LOQTORZI and Medication Guide

Conference Call Information

When: Friday, October 27, 2023, starting at 4:30 p.m. Eastern Time / 1:30 p.m. Pacific Time

To access the conference call, please pre-register through the following link to receive dial-in information and a personal PIN to access the live call: https://register.vevent.com/register/BI5e94411d336341ba89d7e9eed804e892

Please dial-in 15 minutes early to ensure a timely connection to the call.

Webcast Link: View Source

A replay of the webcast will be archived on the "Investors" section of the Coherus website at View Source

On October 27, 2023 ASLAN Pharmaceuticals (Nasdaq: ASLN), a clinical-stage, immunology-focused biopharmaceutical company developing innovative treatments to transform the lives of patients, reported financial results for the third quarter ended September 30, 2023, and provided an update on recent corporate activities (Press release, ASLAN Pharmaceuticals, OCT 27, 2023, View Source [SID1234636405]).

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"At the start of the third quarter, we presented positive topline Phase 2b data from the TREK-AD study showing eblasakimab has the potential to deliver a monthly dosing regimen from initiation of treatment with a competitive efficacy profile. In our recent survey of US physicians, this attribute was considered to be one of the most important in a new therapy for atopic dermatitis (AD) and a compelling advantage to differentiate eblasakimab within the current AD treatment landscape by seventy percent of those surveyed," said Dr Carl Firth, CEO, ASLAN Pharmaceuticals.

"Additionally, data from the TREK-AD study was accepted as a late-breaker oral presentation at the European Academy of Dermatology and Venereology congress in October. We presented a new analysis demonstrating eblasakimab was equally effective in AD patients whose disease was scored as severe, while placebo effects were markedly reduced, leading to a widening in placebo-adjusted efficacy. The correlation of high placebo rates with lower disease severity has been observed in other recent AD studies and highlights the sensitivity of the placebo response to disease severity. As discussed in a recent webinar we hosted with key opinion leaders in dermatology, the absolute efficacy of a drug could be a more reliable measure, and more relevant in the real world, than placebo-adjusted efficacy where there are differences in baseline disease severity. These analyses and others still ongoing, together with the findings from our patient and physician surveys, support our planning of a Phase 3 study of eblasakimab, which we would expect to initiate in 2024 alongside a global commercial partner," Dr Firth added.

Third quarter 2023 and recent business highlights

Q3 and recent clinical developments

•
In July, ASLAN published a perspective article in Annals of Allergy, Asthma and Immunology, in collaboration with Emma Guttmann-Yassky MD, PhD, titled "Targeting type 2 immune activation beyond atopic dermatitis". The article discusses the potential of a therapeutic like eblasakimab to treat a range of Type 2 driven comorbidities beyond AD. The open access article can be read here.
•
In July, ASLAN presented five abstracts showcasing findings related to eblasakimab as posters and oral presentations at the 25th World Congress of Dermatology which took place in Singapore. The posters can be accessed in the "Publications" section of ASLAN’s website.
•
In July, ASLAN announced positive topline data from the Phase 2b dose-ranging TREK-AD study of eblasakimab that met the primary endpoint across three dose arms. Eblasakimab demonstrated the potential for once-monthly dosing from initiation with a competitive efficacy profile in moderate-to-severe AD.
•
In October, ASLAN presented a late-breaker abstract showcasing new data from the TREK-AD study of eblasakimab at the 32nd EADV Congress, in Berlin, Germany. New data from a post-hoc analysis of patients with severe disease (defined as those with a baseline Eczema Area and Severity Index (EASI) score of at least 21), representing 63% of the intent-to-treat patients, show monthly dosing with 600 mg eblasakimab for 16 weeks led to a 74.5% reduction in EASI score (versus 38.0% on placebo, p<0.0001) and EASI-75 of 53.6% (versus 12.9% on placebo, p=0.0009), representing a marked widening in placebo-adjusted efficacy while the response to eblasakimab treatment was maintained. Three additional abstracts on eblasakimab and farudodstat were presented at the congress. The posters can be accessed in the "Publications" section of ASLAN’s website.
•
In October, in collaboration with Dermatology Times, ASLAN published a virtual KOL video series featuring Dr Peter Lio, MD, FAAD showcasing insights from a survey commissioned by ASLAN on US patients’ satisfaction with current AD treatments and physician prescribing habits. The video series can be accessed here.
•
In October, ASLAN co-hosted a panel discussion with a leading Clinical Research Organization entitled, "The Changing Face of Atopic Dermatitis: How the Clinical Trial and Treatment Landscape has Changed in the Seven Years Following Dupilumab’s Introduction" that featured Key Opinion Leaders, Jonathan Silverberg, MD, PhD, MPH (The George Washington University School of Medicine and Healthy Sciences) and April W. Armstrong, MD, MPH (UCLA). ASLAN presented further post-hoc analyses from the TREK-AD study, as well as insights from a recently completed survey of AD patients and US physicians’ attitudes to prescribing treatments for AD. A replay of the event is available here.

Anticipated upcoming milestones

•
Presentation of preliminary results on eblasakimab in a human translational model of chronic obstructive pulmonary disorder (COPD) at the 7th Annual Dermatology Drug Development Summit for Inflammatory Skin Diseases on 2 November.
•
Topline interim data from the FAST-AA study of farudodstat is expected in the first quarter of 2024.
•
A Phase 1 trial of eblasakimab in Japan is expected to be initiated by ASLAN’s partner, Zenyaku Kogyo Co,. in the first half of 2024.
•
ASLAN is conducting continued analyses of the TREK-AD study and plans to submit data on biomarkers and patient reported outcomes for publication at a future scientific congress.
•
An end-of-Phase 2 meeting with the US Food and Drug Administration is expected and subsequent initiation of the Phase 3 clinical program for eblasakimab is expected to occur in 2024.
Third quarter 2023 financial highlights

•
As of September 30, 2023, the Company had cash and cash equivalents of $40.8 million.
•
Cash used in operations for the third quarter of 2023 was $13.7 million compared to $9.1 million in the same period in 2022. Net cash outflow was $1.7M following receipt of $12.0 million in July from Zenyaku Kogyo Co. as an upfront strategic license payment.
•
Research and development expenses were $7.2 million in the third quarter of 2023 compared to $8.0 million in the third quarter of 2022. The decrease was due to lower clinical development and manufacturing costs for the eblasakimab studies following the TREK-AD topline data readout.
•
General and administrative expenses were $3.2 million in the third quarter of 2023 compared to $2.3 million in the third quarter of 2022.
•
Net loss attributable to stockholders for the third quarter of 2023 was $9.7 million compared to a net loss of $10.9 million for the third quarter of 2022.
•
The weighted average number of American Depositary Shares (ADSs) outstanding in the computation of basic loss per share for the second quarter of 2023 was 17.2 million (representing 430.1 million ordinary shares) compared to 13.9 million (representing 348.7 million ordinary shares) for the third quarter of 2022. One ADS is the equivalent of twenty-five ordinary shares.

On October 27, 2023 AbbVie (NYSE:ABBV) reported financial results for the third quarter ended September 30, 2023 (Press release, AbbVie, OCT 27, 2023, View Source [SID1234636404]).

"We delivered another quarter of outstanding results driven by accelerating performance across our non-Humira growth platform, which is demonstrating double-digit growth," said Richard A. Gonzalez, chairman and chief executive officer, AbbVie. "Based upon the strength and momentum of our business, we are once again raising our full-year 2023 guidance as well as our floor EPS outlook for next year. We are also increasing our quarterly dividend, underscoring our confidence in AbbVie’s long-term outlook."

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Note: "Operational" comparisons are presented at constant currency rates that reflect comparative local currency net revenues at the prior year’s foreign exchange rates. 1

Third-Quarter Results

•Worldwide net revenues were $13.927 billion, a decrease of 6.0 percent on a reported basis, or 5.8 percent on an operational basis.

•Global net revenues from the immunology portfolio were $6.783 billion, a decrease of 11.3 percent.
◦Global Humira net revenues of $3.547 billion decreased 36.2 percent. U.S. Humira net revenues were $3.020 billion, a decrease of 39.1 percent. Internationally, Humira net revenues were $527 million, a decrease of 12.6 percent on a reported basis, or 12.2 percent on an operational basis.
◦Global Skyrizi net revenues were $2.126 billion, an increase of 52.1 percent on a reported basis, or 51.9 percent on an operational basis.
◦Global Rinvoq net revenues were $1.110 billion, an increase of 59.8 percent on a reported basis, or 59.6 percent on an operational basis.

•Global net revenues from the oncology portfolio were $1.512 billion, a decrease of 8.4 percent on a reported basis, or 8.6 percent on an operational basis.
◦Global Imbruvica net revenues were $908 million, a decrease of 20.0 percent, with U.S. net revenues of $678 million and international profit sharing of $230 million.
◦Global Venclexta net revenues were $590 million, an increase of 14.6 percent on a reported basis, or 14.0 percent on an operational basis.

•Global net revenues from the neuroscience portfolio were $2.043 billion, an increase of 22.1 percent on a reported basis, or 22.0 percent on an operational basis.
◦Global Botox Therapeutic net revenues were $748 million, an increase of 7.1 percent on a reported basis, or 7.4 percent on an operational basis.
◦Global Vraylar net revenues were $751 million, an increase of 35.4 percent.
◦Global Ubrelvy net revenues were $233 million, an increase of 45.6 percent.
◦Global Qulipta net revenues were $132 million.

•Global net revenues from the aesthetics portfolio were $1.239 billion, a decrease of 4.7 percent on a reported basis, or 4.0 percent on an operational basis.
◦Global Botox Cosmetic net revenues were $620 million, a decrease of 2.7 percent on a reported basis, or 1.7 percent on an operational basis.
◦Global Juvederm net revenues were $321 million, a decrease of 8.6 percent on a reported basis, or 7.9 percent on an operational basis.

•On a GAAP basis, the gross margin ratio in the third quarter was 53.4 percent. The adjusted gross margin ratio was 83.5 percent.

•On a GAAP basis, selling, general and administrative (SG&A) expense was 24.2 percent of net revenues. The adjusted SG&A expense was 23.9 percent of net revenues.

•Research and development (R&D) expense on a GAAP and adjusted basis was 12.4 percent of net revenues, reflecting funding actions supporting all stages of our pipeline.

•Acquired IPR&D and milestones expense was 0.5 percent of net revenues.

•On a GAAP basis, the operating margin in the third quarter was 16.4 percent. The adjusted operating margin was 46.7 percent.

•Net interest expense was $398 million.

•On a GAAP basis, the tax rate in the quarter was 8.8 percent. The adjusted tax rate was 15.7 percent.

•Diluted EPS in the third quarter was $1.00 on a GAAP basis. Adjusted diluted EPS, excluding specified items, was $2.95. These results include an unfavorable impact of $0.04 per share related to acquired IPR&D and milestones expense.
Note: "Operational" comparisons are presented at constant currency rates that reflect comparative local currency net revenues at the prior year’s foreign exchange rates.
2

Recent Events

•AbbVie announced that it submitted applications for a new indication to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for Skyrizi (risankizumab) for the treatment of adult patients with moderately to severely active ulcerative colitis (UC). The submissions are supported by two Phase 3 clinical trials demonstrating Skyrizi achieved the primary endpoint of clinical remission (per Adapted Mayo Score) and key secondary endpoints as an induction and maintenance treatment. Skyrizi is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally.

•AbbVie announced positive topline results from SEQUENCE, a Phase 3 study evaluating Skyrizi versus Stelara (ustekinumab) in patients with moderately to severely active Crohn’s disease (CD) who have failed one or more anti-TNF therapies. In the study, Skyrizi met both primary endpoints (non-inferiority for clinical remission per CDAI at week 24 and superiority of endoscopic remission at week 48) versus Stelara. All secondary endpoints in the trial achieved statistical significance for superiority versus Stelara. Safety results were consistent with the overall safety profile of Skyrizi, with no new safety risks identified.

•AbbVie announced that its Phase 2b study evaluating Rinvoq (upadacitinib) in adults with non-segmental vitiligo (NSV) met the primary endpoint of percent change from baseline in the Facial Vitiligo Area Scoring Index (F-VASI) at week 24 with the 11 mg and 22 mg doses versus placebo. The percent reduction from baseline in F-VASI at week 52 was numerically greater than results at week 24 for all Rinvoq doses. No new safety signals were identified beyond the known safety profile for Rinvoq. Based on these data, AbbVie is advancing its clinical program of Rinvoq in vitiligo to Phase 3.

•At the United European Gastroenterology (UEG) Week 2023, AbbVie shared 23 abstracts, including 11 oral presentations and 12 poster presentations, spanning research on Skyrizi and Rinvoq in both CD and UC. Highlights included late-breaking data from the head-to-head Phase 3 SEQUENCE study evaluating Skyrizi versus Stelara in CD, primary efficacy and safety results from the Phase 3 INSPIRE induction study for Skyrizi in UC, as well as analyses on clinical and endoscopic outcomes from AbbVie’s maintenance trials for Skyrizi and Rinvoq in CD and for Rinvoq in UC.

•At the European Academy of Dermatology and Venereology (EADV) Congress, AbbVie announced new data analyses from the Measure Up 1, Measure Up 2 and AD Up Phase 3 studies that further demonstrated the long-term efficacy and safety profile of Rinvoq among adults and adolescents 12 years and older with moderate to severe atopic dermatitis (AD). Across all 3 studies, response rates for EASI 75 and vIGA-AD 0/1 (co-primary endpoints) and for EASI 90 and WP-NRS 0/1 at week 16 were sustained through week 140 among patients treated with Rinvoq. Safety results were consistent with the known safety profile of Rinvoq, with no new safety signals observed.

•AbbVie announced that the European Commission (EC) granted conditional marketing authorization for Tepkinly (epcoritamab) as a monotherapy for the treatment of adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. Tepkinly is the first and only subcutaneous T-cell engaging bispecific antibody approved for the treatment of this patient population in the European Union (EU). This conditional marketing authorization approval represents AbbVie’s second approved hematological cancer treatment in the EU and is supported by data from the pivotal Phase 1/2 EPCORE NHL-1 clinical trial. Tepkinly is being co-developed by AbbVie and Genmab.

•In August 2023, as part of Inflation Reduction Act (IRA) of 2022, the company’s oncology product Imbruvica, sold in the U.S., was included on the list of products selected for price negotiation by the Centers for Medicare & Medicaid Services (CMS). The selection contributed to a significant decrease in the estimated future cash flows for the product and represented a triggering event which required the company to evaluate the underlying definite lived-intangible asset for impairment. The company utilized a discounted cash flow analysis to estimate the fair value of the intangible asset resulting in a partial impairment of both the gross and net carrying amount. Based on the revised cash flows, the company recorded a pre-tax impairment charge of $2.1 billion to cost of products sold in the condensed consolidated statement of earnings for the third quarter of 2023. The remaining intangible asset carrying value related to Imbruvica in the U.S. totaled $1.8 billion as of September 30, 2023.

•AbbVie announced results from CANOVA, a Phase 3 study evaluating Venclexta (venetoclax) plus dexamethasone (VenDex) for patients with t(11;14)-positive r/r multiple myeloma (MM) who received two or more prior treatments. Data did not demonstrate that the treatment combination significantly improved progression-free survival (PFS), the primary endpoint of the trial. Patients receiving VenDex showed improvement in median PFS of 9.9 months compared to 5.8 months with the combination of study comparator pomalidomide and dexamethasone (PomDex); however, the results did not reach statistical significance. Results were presented at the International Myeloma Society (IMS) Annual Meeting and AbbVie will discuss the data with health authorities to further understand the potential of venetoclax as a biomarker-driven therapy in MM. Venclexta is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

•AbbVie announced that the (EC) approved Aquipta (atogepant) for the prophylaxis of migraine in adults who have four or more migraine days per month. The approval makes Aquipta the only once-daily oral calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) treatment in the EU for the preventive treatment of both chronic and episodic migraine. The approval is based on two pivotal Phase 3 studies that demonstrated statistically significant reduction in mean monthly migraine days with Aquipta compared to placebo in adult patients with both chronic and episodic migraine.

•Allergan Aesthetics announced positive topline results from the second of three Phase 3 clinical studies evaluating Botox Cosmetic (onabotulinumtoxinA) for the treatment of moderate to severe platysma prominence associated with platysma muscle activity. All primary and secondary endpoints were met for this study and results were consistent with findings from the first Phase 3 study. Results support Botox Cosmetic as a potential treatment option for moderate to severe platysma prominence and data will be included as part of an upcoming FDA regulatory submission expected near the end of the year. If approved, Botox Cosmetic will be the first and only neurotoxin for this indication.

•Allergan Aesthetics announced positive topline results from two pivotal Phase 3 clinical studies evaluating trenibotulinumtoxinE (BoNT/E) for the treatment of moderate to severe glabellar lines. All primary and secondary endpoints were met for both studies and results support trenibotulinumtoxinE as a novel botulinum neurotoxin serotype E characterized by a rapid onset of action as early as 8 hours after administration and short duration of effect within 2-3 weeks.

•AbbVie announced that it exercised its exclusive right to acquire of Mitokinin, a discovery-stage biotechnology company developing a potentially first-in-class disease-modifying treatment for Parkinson’s Disease (PD). Mitokinin’s lead compound, a selective PINK1 activator, is designed to address mitochondrial dysfunction that is believed to be a major contributing factor to PD pathogenesis and progression.

Full-Year 2023 Outlook

AbbVie is raising its adjusted diluted EPS guidance for the full year 2023 from $10.86 – $11.06 to $11.19 – $11.23, which includes an unfavorable impact of $0.27 per share related to acquired IPR&D and milestones expense incurred year-to-date through the third quarter 2023. The company’s 2023 adjusted diluted EPS guidance excludes any impact from acquired IPR&D and milestones that may be incurred beyond the third quarter of 2023, as both cannot be reliably forecasted.

AbbVie Raises 2024 EPS Guidance Floor

AbbVie is raising its adjusted diluted EPS guidance floor for the full year 2024 from $10.70 to $11.00, which excludes any impact from acquired IPR&D and milestones, as both cannot be reliably forecasted. This is an update to guidance that was initially issued in February 2023 as part of AbbVie’s fourth quarter 2022 earnings call. As a result of this update, AbbVie does not expect adjusted diluted EPS for full year 2024 to be below $11.00 per share. The company will issue its formal 2024 adjusted diluted EPS guidance range in conjunction with fourth quarter 2023 results.

Company Declares Dividend Increase of 4.7 Percent

AbbVie is announcing today that its board of directors declared an increase in the company’s quarterly cash dividend from $1.48 per share to $1.55 per share beginning with the dividend payable on February 15, 2024 to shareholders of record as of January 16, 2024. This reflects an increase of approximately 4.7 percent, continuing AbbVie’s strong commitment to returning cash to shareholders through a growing dividend. Since the company’s inception in 2013, AbbVie has increased its quarterly dividend by more than 285 percent. AbbVie is a member of the S&P Dividend Aristocrats Index, which tracks companies that have annually increased their dividend for at least 25 consecutive years.

On October 27, 2023 SN Bioscience Co., Ltd. (CEO Younghwan Park) reported the results of the phase 1 clinical study of SNB-101, a nanoparticle anti-cancer new drug pipeline, at ESMO (Free ESMO Whitepaper) Congress 2023 held in Madrid, Spain from October 20 to 24 (Press release, SN BioScience, OCT 27, 2023, View Source [SID1234636396]). This phase 1 clinical study was conducted to evaluate the safety and tolerability of SNB-101 administered to 21 patients with solid tumors in Korea and to determine the recommended dose for phase 2. CHA Bundang Medical Center (Professor Joo-Hang Kim), Catholic University of Korea Seoul ST. Mary’s Hospital (Professor Myung A Lee), and Severance Hospital of the Yonsei University (Professor Sun Young Rha) participated in this study.

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In this phase 1 clinical study, patients with various solid cancers, such as small cell lung cancer, non-small cell lung cancer, gastric cancer, esophageal cancer, head and neck cancer, and rectal cancer, who failed existing standard therapy were enrolled, and they had previously experienced 1st to 9th lines of treatment.

The results of the phase 1 study showed excellent safety in the dosage range (5 to 50 mg/m2 as of SN-38) and did not reach the maximum tolerable dose (MTD) even when all the cohorts were consumed. The most common adverse drug reactions were hematological, such as neutropenia, and were well manageable. In particular, diarrhea of grade 3 or higher, a major adverse drug reaction that frequently occurs with irinotecan, a drug with same active moiety, was not observed. Accordingly, it was evaluated to have excellent safety and tolerability compared to the competitive drugs.

In terms of the efficacy evaluation results, out of a total of 21 patients, partial response (PR) was 14.3% (3 patients, small cell lung cancer, non-small cell lung cancer, rectal cancer), and stable disease (SD) was 28.6% (6 patients, small cell lung cancer, non-small cell lung cancer, rectal cancer, head and neck cancer, gastric cancer), and progressive disease (PD) was 57.1% (12 patients). The disease control rate (DCR) of all patients was 42.9%, well demonstrating the characteristics of general cytotoxic anti-cancer drugs. In particular, in the high dose group (40~50mg/m2), the DCR was 83.3%, well indicating dose dependency.

SNB-101 is a polymeric nanoparticle with an average particle size of approximately 100 nm, and in the preclinical studies, its distribution to the lungs was significantly higher than that of the anti-cancer drugs in conventional delivery. That aligns well with the efficacy results in lung-related tumors such as small cell lung cancer and non-small cell lung cancer from preclinical and phase 1 clinical studies. Based on the results, SN Bioscience plans to conduct multinational phase 2 clinical study targeting the small cell lung cancer in 2024.

For small cell lung cancer, which is one of the areas with very high unmet medical needs, cisplatin + etoposide combination is currently used as the first line standard therapy. Second line therapies include lurbinectedin (product name: Zebzelca), which was recently approved as an orphan drug, and topotecan and paclitaxel, which are traditional chemotherapeutic regimen. According to the NCCN (National Comprehensive Cancer Network) guidelines, treatments are so limited that clinical studies are listed as second line treatment options. In preclinical studies, SNB-101 showed superior efficacy over the first line therapies as well as the second line therapies that are approved for small cell lung cancer. The goal of phase 2 clinical study is to show the superiority over competitive drugs as monotherapy and/or combination with immunotherapy, based on which, SN BioScience plans to enter the global market through expedited approval process after completing phase 2 clinical study.

[SNB-101]

SNB-101 is the world’s first nano-anti-cancer drug in which the active metabolite (SN-38) of Irinotecan, a commercially available anti-cancer drug, is active ingredient, and is applied with double nanomicelle technology, a core platform technology of SN Bioscience. SNB-101 is expected to secure new indications as it does not require a metabolic step for activation as well as the advantage of directly administering SN-38, an active metabolite. SNB-101 is a polymeric nanoparticle of approximately 100 nm characterized by a high accumulation rate, especially in the lung and tumor tissue, when administered intravenously, and has shown a wide range of efficacy in solid cancers such as small cell lung cancer, gastric cancer, colon cancer, and pancreatic cancer in preclinical studies. In addition, since it shows a synergistic effect even when used in combination with commercially available immune-anti-cancer drugs, targeted anti-cancer drugs, and chemical anti-cancer drugs, the possibility of its development as a combination therapy in the future is also very high. SNB-101 has secured mass production technology, which is one of the barriers to the development of nanomedicines and is being produced as a sterile product by a contract manufacturing organization (CMO) specializing in anti-cancer drugs that has received EU GMP certification. Furthermore, the US FDA has designated SNB-101 for orphan drug on SCLC based on the medical needs and its preclinical outcome.