On April 19, 2021 Seagen Inc. (Nasdaq:SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported the U.S. Food and Drug Administration (FDA) filed two supplemental Biologics License Application (sBLA) submissions for PADCEV (enfortumab vedotin-ejfv) for review as part of the Real-Time Oncology Review (RTOR) pilot program (Press release, Seagen, APR 19, 2021, View Source [SID1234578180]). The applications were granted Priority Review, with a target action date of August 17, 2021. The review of both applications will also be conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence.

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The FDA’s RTOR program aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible. Project Orbis provides a framework for concurrent submission and review of oncology drugs among participating international partners. The first sBLA is based on the phase 3 EV-301 trial and seeks to convert PADCEV’s accelerated approval to regular approval. The second sBLA, based on the pivotal trial EV-201’s cohort 2, requests an expansion of the current indication to include patients with locally advanced or metastatic urothelial cancer who have been previously treated with a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and are ineligible for cisplatin. Results from EV-301 were published in the New England Journal of Medicine.Results from EV-301 and EV-201 cohort 2 were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium.

"With our recent regulatory submissions, we intend to provide the highest level of clinical evidence supporting PADCEV use – overall survival data from a randomized phase 3 trial – and expand availability in multiple countries where there is unmet medical need," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas.

"These FDA filings, along with regulatory submissions outside of the United States under our collaboration with Astellas, are important steps in our shared goal of bringing PADCEV to more patients with advanced urothelial cancer," said Roger Dansey, M.D., Chief Medical Officer of Seagen.

Health authorities in Australia and Canada will evaluate data from EV-301 and EV-201 for initial registrations under Project Orbis. In March, the companies announced regulatory submissions in Japan and the European Union.

Urothelial cancer is the most common type of bladder cancer (90 percent of cases) and can also be found in the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.1 Globally, approximately 573,000 new cases of bladder cancer and more than 212,000 deaths are reported annually.2

In 2019, PADCEV received accelerated approval in the U.S. for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic urothelial cancer setting. PADCEV is currently only approved for use in the U.S.

About the EV-301 Trial

The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized phase 3 trial designed to evaluate enfortumab vedotin versus physician’s choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in approximately 600 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and a platinum-based therapy.3 The primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.

About the EV-201 Trial

The EV-201 trial (NCT03219333) is a single-arm, dual-cohort, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (cohort 2). The trial enrolled 128 patients in cohort 1 and 91 patients in cohort 2 at multiple centers internationally.4 The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.

PADCEV (enfortumab vedotin-ejfv) U.S. Important Safety Information

Warnings and Precautions

Skin reactions: Severe cutaneous adverse reactions, including fatal cases of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later.

Skin reactions occurred in 54% of the 310 patients treated with PADCEV in clinical trials. Twenty-six percent (26%) of patients had maculopapular rash and 30% had pruritus. Grade 3-4 skin reactions occurred in 10% of patients and included symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In one clinical trial, the median time to onset of severe skin reactions was 0.8 months (range: 0.2 to 5.3). Of the patients who experienced rash, 65% had complete resolution and 22% had partial improvement.

Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines as clinically indicated. Withhold PADCEV and consider referral for specialized care for severe (Grade 3) skin reactions, suspected SJS, or TEN. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis, in those with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. In one clinical trial, 8% of patients developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months (range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation, 19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.

Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes. Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

Infusion site extravasation: Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 310 patients, 1.3% of patients experienced skin and soft tissue reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. One percent (1%) of patients developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

Embryo-fetal toxicity: PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

Adverse Reactions

Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).

Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).

The most common adverse reactions (≥20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

Lab Abnormalities

In one clinical trial, Grade 3-4 laboratory abnormalities reported in ≥5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).

Drug Interactions

Effects of other drugs on PADCEV Concomitant use with a strong CYP3A4 inhibitor may increase free MMAE exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with strong CYP3A4 inhibitors.

Specific Populations

Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

On April 19, 2021 Nicox SA (Euronext Paris: FR0013018124, COX), an international ophthalmology company, reported a business update and financial highlights for Q1 2021 for Nicox SA and its subsidiaries (the "Nicox Group"), and updated key expected value-inflection milestones (Press release, NicOx, APR 19, 2021, View Source [SID1234578179]).

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Key Expected Milestones
NCX 470 Phase 3 program in glaucoma: Nicox’s lead clinical product candidate, NCX 470, is a novel nitric oxide (NO)-donating prostaglandin analog currently in two multi-regional Phase 3 trials for the evaluation of the safety and efficacy of NCX 470 ophthalmic solution, 0.1%, against latanoprost ophthalmic solution, 0.005%, for lowering of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Top-line results are currently expected in Q2 2022 for Mont Blanc and in Q4 2022 for Denali.
NCX 4251 Phase 2b trial, Mississippi in blepharitis: NCX 4251 is a novel patented ophthalmic suspension of fluticasone propionate nanocrystals. Mississippi is evaluating once-daily dosed NCX 4251 0.1% versus placebo for the treatment of acute exacerbations of blepharitis. Top-line results are currently expected in Q4 2021.
We expect to enter into additional agreements for ZERVIATE (cetirizine ophthalmic solution), 0.24%, further expanding the licensed territories and increasing potential future revenue.
Bausch + Lomb is planning to launch VYZULTA (latanoprostene bunod ophthalmic solution), 0.024%, in Taiwan in 2021 and in South Korea in 2022.
First Quarter 2021 and Recent Operational Highlights
Innovative pipeline

50% of patients in the NCX 470 Mont Blanc Phase 3 glaucoma clinical trial have now been randomized with top-line results currently on track to be announced during Q2 2022.
Ocumension Therapeutics, Nicox’s partner for NCX 470 in China and Southeast Asia, received approval from China’s Center for Drug Evaluation of the National Medical Products Administration to conduct the Chinese part of the ongoing NCX 470 Denali Phase 3 trial for the lowering of IOP in patients with open angle glaucoma or ocular hypertension. Ocumension is also currently evaluating ZERVIATE in a confirmatory Phase 3 clinical trial in China, which was initiated in December 2020 to support a New Drug Application there for the treatment of ocular itching associated with allergic conjunctivitis.
Pre-clinical IOP-lowering results on a new class of non-prostaglandin analog, NO-donating compounds, were published in the Journal of Ocular Pharmacology and Therapeutics, a leading scientific journal. Elevated IOP is one of the principal risk factors of open-angle glaucoma. The NO-mediated IOP-lowering effect in this new class of compounds is enhanced by concomitant action of phosphodiesterase type-5 inhibition within the same molecule. NCX 1728 is the first in this new class of compounds to be selected for development.
Commercial products

VYZULTA has been approved in Brazil, the largest market in Latin America. VYZULTA is commercialized by Nicox’s exclusive worldwide partner Bausch + Lomb in the U.S. (2017), Canada (2019), Argentina (2020), Mexico (2020) and Hong Kong (2020), and is now approved in 5 other territories – Brazil, Colombia, South Korea, Taiwan and Ukraine.
The number of prescriptions1 for VYZULTA in the U.S. increased by 10.6% in the first quarter of 2021 compared to the first quarter of 2020.
ZERVIATES. prescriptions2 increased by 29.1% in the first quarter of 2021 over the fourth quarter of 2020. ZERVIATE has been commercialized in the U.S. since March 2020 by Nicox’s U.S. partner Eyevance Pharmaceuticals. Eyevance has entered into a partnership with Hikma Pharmaceuticals for the co-promotion of ZERVIATE in the U.S. who will be responsible for promoting ZERVIATE to U.S. healthcare professionals working outside the eyecare specialty, with all sales continuing to be booked by Eyevance, and on which Nicox will receive royalties.
Corporate

Nicox amended its bond financing agreement with Kreos Capital, introducing an additional one-year period of interest-only payments on the outstanding principal starting on February 1, 2021, and an extension of the overall period of the loan by 6 months to July 2024. The new one-year interest-only period is expected to provide approximately €5.5 million of additional flexibility for investment in development activities in 2021. The interest rate of the bonds remains unchanged as a result of this amendment.
We continue to closely watch the spread and impact of the COVID-19 pandemic and we will provide an update of any delays.

First Quarter 2021 Financial Highlights
As of March 31, 2021, the Nicox Group had cash and cash equivalents of €42.0 million as compared with €47.8 million at December 31, 2020. Net revenue3 for the first quarter of 2021 was €0.6 million (entirely composed of net royalty payments). Net revenue3 for the first quarter of 2020 was €1.7 million (including €0.7 million of net royalty payments).

As of March 31, 2021, the Nicox Group had financial debt of €17.8 million consisting of €15.8 million in the form of a bond financing agreement with Kreos Capital signed in January 2019 and a €2 million credit agreement with Société Générale and LCL, guaranteed by the French State, and granted in August 2020 in the context of the COVID-19 pandemic.

On April 19, 2021 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug designation for CA-4948, a first-in-class, small molecule inhibitor of IRAK4 and Curis’s most advanced therapeutic in clinical development. CA-4948 targets IRAK4-L, the oncogenic isoform of IRAK4 preferentially expressed by the majority of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) and has shown broad clinical activity in Phase 1 trials in patients with relapsed or refractory (R/R) AML/MDS (Press release, Curis, APR 19, 2021, View Source [SID1234578178]).

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"We are pleased to take this important next step in unlocking the potential of CA-4948 to offer a safe and transformative, disease-modifying alternative treatment for patients on the AML/MDS spectrum," said James Dentzer, chief executive officer of Curis. "Receiving Orphan Drug designation for CA-4948 in AML and MDS represents a significant milestone in our mission of slowing or preventing the progression of disease in patients with these rare hematological malignancies."

Orphan Drug Designation is granted by the FDA to drugs intended to treat rare disorders that affect fewer than 200,000 people in the U.S. The designation can provide development and commercial incentives, including eligibility for seven years of market exclusivity in the U.S. after product approval, FDA assistance in clinical trial design and exemption from FDA user fees.

On April 19, 2021 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer and infectious diseases, reported that the U.S. Food and Drug Administration (US FDA) has requested additional information regarding its Chimeric Antigen Receptor-T cell therapy (CAR-T) being developed in partnership with Moffitt Cancer Center (MCC) (Press release, Anixa Biosciences, APR 19, 2021, View Source [SID1234578176]).

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The study under the Investigational New Drug (IND) application has been placed on clinical hold pending submission of additional information requested by the FDA. Within the next 30 days, it is expected that the FDA will provide a letter to MCC with detailed and specific information requested. MCC will assemble and submit information addressing the request as soon as possible thereafter. Successive to the submission, the FDA will continue its review of the IND.

This technology is an autologous cell therapy that requires the manufacture of a unique drug product for each individual patient. The therapeutic product is comprised of engineered T-cells that target the follicle stimulating hormone receptor (FSHR). FSHR is found at immunological levels exclusively on the granulosa cells of the ovaries. Since the target is a hormone receptor, this technology is also known as CER-T (Chimeric Endocrine Receptor T-cell) therapy, a new type of CAR-T.

Dr. Amit Kumar, President and CEO of Anixa Biosciences, stated, "We are eagerly awaiting guidance from the FDA with details about the specific information requested to clear the IND, enabling initiation of clinical trials."

On April 19, 2021 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that health-related quality of life (HRQoL) data from the Phase 3 portion of the SEAL (Selinexor in Advanced Liposarcoma) study were published online in Future Oncology (Press release, Karyopharm, APR 19, 2021, View Source [SID1234578172]). The SEAL study evaluated twice weekly, single agent selinexor, the Company’s first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, versus matching placebo in patients with advanced unresectable dedifferentiated liposarcoma (DDLPS) who have experienced disease progression following at least two prior therapies. XPOVIO (selinexor) is currently approved by the U.S. Food & Drug Administration (FDA) for the treatment of relapsed or refractory multiple myeloma and relapsed or refractory diffuse large B-cell lymphoma; XPOVIO has not been approved for the treatment of DDLPS and, therefore, its safety and efficacy for that patient population have not been established.

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"The Phase 3 SEAL study suggests that selinexor has enhanced clinical activity and a manageable safety profile in patients with DDLPS, a very rare and aggressive form of cancer where there are very few treatment options available. In addition to meeting its primary endpoint with a statistically significant improvement in progression-free survival (PFS), treatment with selinexor also resulted in improvements in key quality of life parameters as compared to patients treated with placebo," said Jatin Shah, MD, Chief Medical Officer of Karyopharm. "The results highlight that the reduction in tumor growth, as measured by objective radiographic PFS, is accompanied by clinically important reductions in pain, with minimal effects on other aspects of quality of life. Since pain is one of the most devastating symptoms associated with advanced and progressing DDLPS, the significant reduction in pain, and a delay in the time to definitive deterioration reported by patients in the selinexor arm, combined with the convenience of an orally administered therapy, could represent a meaningful clinical benefit to patients."

"We are pleased to see the first set of data from the Phase 3 SEAL study now published in a peer-reviewed medical journal," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "These data continue to support our overarching development strategy to pursue additional solid tumor indications where we believe selinexor can demonstrate meaningful clinical activity both as a single agent, and more importantly, as part of future combination regimens for patients battling cancer."

The Phase 3 SEAL Study Health-Related Quality of Life Results

The published SEAL study results were based on the randomized, double blind, placebo-controlled, cross-over, Phase 3 portion of the study, which evaluated oral selinexor versus matching placebo in 285 adult patients with advanced unresectable DDLPS. The secondary endpoint of the SEAL study measured HRQoL outcomes by using the EORTC QLQ-C30 questionnaire, which was completed by 255 patients in the study. Overall, the results showed that pain scores worsened in the placebo arm compared to the selinexor arm across all post-baseline visits, though some visits were not statistically significant. The patients who received twice-weekly selinexor also reported lower rates and slower worsening of pain over time and a longer time to marked clinical deterioration of pain compared to patients treated with placebo. Median time to next treatment was also significantly longer in patients receiving selinexor compared to those receiving placebo. These results indicate that reduction in tumor growth (as measured by objective radiographic PFS) is accompanied by clinically important reduction in pain, with minimal effects on other aspects of quality of life.

About the SEAL Study

SEAL (Selinexor in Advanced Liposarcoma) was a Phase 2/3, randomized, double blind, placebo-controlled, multicenter study (NCT02606461) designed to evaluate the efficacy and safety of twice-weekly, 60mg fixed dose of selinexor in patients with advanced unresectable dedifferentiated liposarcoma following at least two prior therapies. The Phase 3 portion of the study enrolled 285 patients (2:1 randomization). Patients on the placebo arm with confirmed progressive disease were permitted to cross over to the selinexor treatment arm. The primary endpoint of the study was PFS and secondary endpoint measured HRQoL outcomes. In the study, selinexor was associated with a 30% reduction in the time to disease progression or death in the Phase 3 portion (hazard ratio (HR)=0.70; p=0.023, medians 2.83 months on selinexor compared to 2.07 months on placebo).

The most common treatment-related adverse events (AEs) were cytopenias, along with gastrointestinal and constitutional symptoms and were consistent with those previously reported from other selinexor studies. Most AEs were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (81%), decreased appetite (60%), fatigue (51%), and vomiting (49%) and were mostly Grade 1 and 2 events. The most common Grade 3 and 4 treatment-related AEs were anemia (19%), hyponatremia (11%), thrombocytopenia (10%) and asthenia (10%).

About Liposarcoma

Liposarcoma is a rare type of cancer that occurs in the fat cells in the body, most often in the muscles of the limbs or abdomen. Dedifferentiated liposarcoma is a high grade type of liposarcoma that grows more aggressively than a low grade, well differentiated liposarcoma and is associated with poorer prognosis.1 Liposarcoma accounts for approximately 20% of all soft tissue sarcomas.2 In liposarcoma, the risk of recurrence and metastasis increases with higher grade disease.3

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. The safety and efficacy of selinexor for use in in patients with DDLPS has not been established; selinexor has not been approved for this use by the U.S. Food and Drug Administration (FDA) or any other regulatory agency. Karyopharm received accelerated approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have 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. NEXPOVIO (selinexor) has also been granted conditional marketing authorization in combination with dexamethasone for adult patients with heavily pretreated multiple myeloma by the European Commission. Karyopharm’s supplemental New Drug Application requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA on December 18, 2020. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have 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 (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection(21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.