On October 6, 2018 Veracyte, Inc. (Nasdaq: VCYT) reported that new findings from six studies reinforcing the "real world" performance of the next-generation Afirma Genomic Sequencing Classifier (GSC) and the Afirma Xpression Atlas in thyroid cancer diagnosis were presented at the 88th Annual Meeting of the American Thyroid Association (ATA) (Press release, Veracyte, OCT 6, 2018, View Source [SID1234529797]). The meeting is being held October 3-7 in Washington, D.C.

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Researchers from leading institutions presented posters showing that use of the Afirma GSC at their respective centers significantly increased the identification of benign thyroid nodules among those deemed indeterminate – not clearly benign or malignant – following cytopathology review, compared to the original Afirma test.

The Ohio State University – Researchers compared results of 113 indeterminate samples that were tested with the Afirma GSC to those of 403 samples using the earlier version of the test (the Afirma Gene Expression Classifier, or GEC). The Afirma GSC identified 74.1 percent of the nodules as benign, compared to 48.4 percent with the GEC, an increase of 53 percent. The overall surgery rate among all patients who underwent genomic testing decreased by more than half – from 42.2 percent with the GEC to 20.2 percent with the GSC.
Cleveland Clinic – Comparing results of 46 samples tested with the Afirma GSC between July 2017 and December 2017 with 182 samples tested with the original test between December 2011 and July 2017, researchers found that the GSC identified 67.4 percent as benign, compared to 41.8 percent with the GEC – an increase of 61 percent. The overall surgery rate for nodules tested with the GSC was 32.6 percent, compared to 47.3 percent with the original test, a decrease of 31 percent.
Brigham and Women’s Hospital – Researchers evaluated results for 583 thyroid nodules tested with either the Afirma GSC (n=97) or GEC (n=486) between 2011 and 2018. They found that the Afirma GSC identified 64.9 percent of nodules as benign, compared to 47.9 percent with the GEC, an increase of 35 percent.
"Our results show that with the improved testing, we sent significantly fewer patients to surgery," said Dr. Christian Nasr, medical director of the Thyroid Center in the Endocrinology & Metabolism Institute at Cleveland Clinic in Cleveland, Ohio. "Additionally, when patients went to surgery following ‘suspicious’ results, we were more likely to find cancer. Our findings suggest that the next-generation test can help more patients avoid unnecessary thyroid surgery, while focusing healthcare resources on the patients who are more likely to need them."

Additionally, in two oral presentations, researchers shared the first "real world" Afirma Xpression Atlas data, providing insights into the distribution of a wide range of gene variants and fusions across key categories of indeterminate thyroid nodules and Afirma GSC results. For example, among 13,549 indeterminate thyroid nodules evaluated using the Afirma GSC and Xpression Atlas, more than a quarter (25.9 percent) of GSC-suspicious nodules (in primary risk categories known as Bethesda III/IV) contained RAS variants. Additionally, RET, NTRK, BRAF and ALK fusions were only found in GSC-suspicious, versus GSC-benign, cases (in all Bethesda categories).

"Having detailed genomic information about thyroid nodules that are malignant or suspicious for cancer may in some cases help inform surgical decision-making for these patients," said Dr. Allan C. Golding of Memorial Healthcare System in Hollywood, Fla. "Additionally, the wide range of gene alterations detected by the Xpression Atlas may provide further insights into pathway activation and potential cancer treatment targets for patients with thyroid cancer."

The field of precision medicine is progressing rapidly, and multiple targeted therapies are in clinical trials or have been approved for treatment of advanced cancers that harbor specific genomic alterations. In the new data presented at the ATA conference, genomic changes (or alterations) targeted by these new therapies were identified in Afirma GSC-suspicious cases by the Xpression Atlas.

"The new data shared at the ATA annual meeting add to the growing library of real-world evidence demonstrating the Afirma GSC’s performance across multiple institutions in reducing unnecessary surgeries in thyroid cancer diagnosis," said Bonnie Anderson, Veracyte’s chairman and chief executive officer. "Additionally, these new study data for the Afirma Xpression Atlas demonstrate the ability of our robust RNA sequencing platform to provide rich genomic content that may help inform surgery decisions and treatment options for patients with suspected or confirmed thyroid cancer. The extensive gene alteration data that it provides becomes increasingly important in the era of targeted therapies."

For more information, please visit the Veracyte Booth #201 or www.afirma.com/ATA2018.

About Afirma

Veracyte’s Afirma solution provides a comprehensive offering in thyroid cancer diagnosis for physicians evaluating patients with thyroid nodules. The Afirma Genomic Sequencing Classifier combines RNA sequencing data with machine learning to identify patients with benign thyroid nodules among those with indeterminate cytopathology results in order to avoid unnecessary surgery and preserve the thyroid. Since the commercial introduction of Afirma in 2011, Veracyte has performed over 100,000 genomic tests, and estimates it has saved more than 40,000 patients from unnecessary thyroid surgery and removed an estimated $800 million in surgery costs from the healthcare system. The Afirma classifier is proven in over 20 published clinical studies, is included in most leading clinical guidelines and is covered as medically necessary by Medicare and all major U.S. health plans. The company’s Afirma Xpression Atlas platform, introduced in May 2018, provides extensive genomic data that may inform surgery strategy and treatment options for patients with thyroid nodules that are suspicious for cancer or cancerous. The RNA sequencing-based platform measures 761 DNA variants and 130 RNA fusions in over 500 genes shown to be associated with thyroid cancer on thyroid nodule fine needle aspiration samples.

On October 6, 2018 Blueprint Medicines Corporation (NASDAQ: BPMC), a leader in discovering and developing targeted kinase medicines for patients with genomically defined diseases, reported the presentation of updated data from the ongoing Phase 1 ARROW clinical trial of BLU-667, an investigational precision therapy targeting RET alterations, including resistance mutations (Press release, Blueprint Medicines, OCT 6, 2018, View Source [SID1234529798]). The new results showed that BLU-667 was highly active and well-tolerated in patients with advanced RET-altered medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC), with increased activity observed with higher dose levels and longer treatment durations.

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The reported data showed 90 percent of evaluable patients with MTC and PTC had radiographic tumor reductions, regardless of RET alteration type or prior multi-kinase inhibitor (MKI) therapy. In addition, the response rate was 62 percent in patients with MTC treated once daily (QD) with BLU-667 at doses of 300 to 400 mg for at least 24 weeks. In the MTC and PTC populations, all responders across dose levels and all patients treated at 400 mg QD remain on study. Safety results were consistent with prior data, and the majority of adverse events (AEs) were Grade 1. These results were as of a data cutoff date of September 14, 2018 and were reported today in an oral presentation at The 88th Annual Meeting of the American Thyroid Association (ATA).

"Existing treatment of medullary and papillary thyroid cancer with multi-kinase inhibitors is limited by frequent dose modifications or interruptions due to off-target toxicities, reducing the opportunity for a meaningful or sustained response," said Andy Boral, M.D., Ph.D., Chief Medical Officer of Blueprint Medicines. "These new data showed selectively targeting RET alterations with BLU-667 was well-tolerated and enabled durable responses. Importantly, response rates were high for patients with prolonged time on therapy at higher dose levels, demonstrating that potent and sustained target inhibition leads to improved patient outcomes. We believe these results begin to reveal the potential of BLU-667 to transform the care of patients with RET-altered thyroid cancer, and we look forward to seeing the data continue to mature as additional patients are treated at the recommended phase 2 dose for longer durations."

Based on the encouraging data reported to date, Blueprint Medicines has expanded enrollment targets for the ARROW trial to further evaluate the safety and efficacy of BLU-667 in a broader patient population and, ultimately, to support potential registration.

Data Highlights from the Ongoing Phase 1 ARROW Clinical Trial

The data presented included all patients enrolled in the Phase 1 ARROW clinical trial as of May 9, 2018 and included follow-up on these patients through the data cutoff date of September 14, 2018. Of the 69 patients who had been treated with BLU-667 in the dose escalation and expansion portions of the trial, 42 had RET-altered thyroid cancer, including 37 with MTC and five with PTC. In the dose escalation portion, patients were treated at dose levels ranging from 30 mg to 600 mg QD or up to 300 mg twice daily. In the expansion portion, patients were treated at the recommended phase 2 dose of 400 mg QD.

Clinical Activity Data

As of the data cutoff date, 35 patients with MTC and four patients with PTC were evaluable for response assessment by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Overall, 90 percent of MTC and PTC patients with measurable target lesions had radiographic tumor reductions.

In patients with MTC, response assessments showed increased clinical activity with higher dose levels and longer treatment durations. Across all evaluable MTC patients, the overall response rate (ORR) was 49 percent, including one patient with a confirmed complete response (CR) and 16 patients with a partial response (PR; two pending confirmation). In patients with MTC treated with 300 to 400 mg QD for at least 24 weeks, the response rate was 62 percent, including one patient with a confirmed CR and seven patients with a confirmed PR.

In patients with PTC, two of four evaluable patients had a confirmed PR, and all evaluable patients with PTC had radiographic tumor shrinkage.

The data also showed encouraging evidence of durable activity. All patients with MTC and PTC who responded to BLU-667 remain on treatment as of the data cutoff date. In addition, all patients treated at 400 mg QD are continuing on therapy. Patients with the longest treatment durations remain on therapy for more than 15 months.

Anti-tumor activity was observed regardless of prior MKI therapy or RET alteration. Similar response rates were observed in MTC patients who were MKI-experienced (47 percent; 8/17 patients) and MKI-naïve (50 percent; 9/18 patients). In addition, clinical responses were observed in patients with common activating mutations in MTC (e.g., M918T) and fusion partners in PTC (e.g., NCO4A and CCDC6). A clinical response was also observed in the one evaluable MTC patient with a germline V804M gatekeeper mutation.

Safety Data

The reported data showed that across 69 patients, BLU-667 was well-tolerated as of the data cutoff date. Most AEs were Grade 1, and only two patients discontinued therapy due to a treatment-related AE (Grade 3 increased alanine aminotransferase in a patient with liver metastases and Grade 2 pneumonitis). Treatment-emergent AEs (regardless of relationship to BLU-667) reported by investigators (≥15 percent) most commonly were constipation (35 percent), increased aspartate aminotransferase (33 percent), anemia (30 percent), hypertension (30 percent), decreased white blood cell count (29 percent), diarrhea (28 percent), neutropenia (28 percent), increased alanine aminotransferase (25 percent), increased blood creatinine (23 percent), fatigue (19 percent) and headache (17 percent). Grade 3 or higher treatment-related AEs occurring in two or more patients included anemia, hypertension, decreased white blood cell count, diarrhea and neutropenia.

About the Phase 1 ARROW Clinical Trial of BLU-667

ARROW is a Phase 1 clinical trial designed to evaluate the safety, tolerability and efficacy of BLU-667 in multiple ascending doses in adults with RET-altered non-small cell lung cancer (NSCLC), MTC and other advanced solid tumors. The trial consists of two parts: a dose escalation portion and an expansion portion. Enrollment in the dose escalation portion is complete, and the expansion portion has been initiated and is actively enrolling patients in six defined cohorts at the recommended phase 2 dose of 400 mg QD: (1) RET-altered NSCLC patients previously treated with an MKI, (2) RET-altered NSCLC patients who have not previously received any MKI treatment, (3) MTC patients previously treated with an MKI, (4) MTC patients who have not previously received any MKI treatment, (5) patients with other RET-altered solid tumors and (6) RET-altered solid tumor patients with prior selective RET tyrosine kinase inhibitor. Trial objectives include assessing response, pharmacokinetics, pharmacodynamics and safety. The trial is designed to enroll approximately 190 patients across all six expansion cohorts, at multiple sites in the United States, European Union and Asia.

Patients and physicians interested in the ARROW clinical trial can contact the Blueprint Medicines study director at [email protected] or 1-617-714-6707. Additional details are available at www.arrowtrial.com or www.clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03037385).

About RET-Altered Solid Tumors

RET activating fusions and mutations are a key disease driver in many cancer types, including NSCLC and MTC. RET fusions are implicated in approximately 1 to 2 percent of patients with NSCLC and approximately 10 percent of patients with PTC, while RET mutations are implicated in approximately 60 percent of patients with MTC. In addition, oncogenic RET alterations are observed at low frequencies in colorectal, breast, pancreatic and other cancers, and RET fusions have been observed in patients with treatment-resistant, EGFR-mutant NSCLC.

Currently, there are no approved therapies that selectively target RET-driven cancers, though there are several approved MKIs with RET activity being evaluated in clinical trials. Thus far, clinical activity attributable to RET inhibition has been uncertain for these inhibitors, likely due to insufficient inhibition of RET and off-target toxicities. There is a need for precision therapies that provide durable clinical benefit by selectively targeting RET alterations and resistance mutations.

About BLU-667

BLU-667 is an investigational, once-daily oral precision therapy specifically designed for highly potent and selective targeting of oncogenic RET fusions, mutations and resistance mutations. In preclinical studies, BLU-667 consistently demonstrated sub-nanomolar potency against the most common RET fusions, activating mutations and resistance mutations. In addition, BLU-667 demonstrated markedly improved selectivity for RET compared to approved MKIs, including more than 80-fold improved potency for RET versus VEGFR2. By suppressing primary and secondary mutants, BLU-667 has the potential to overcome and prevent the emergence of clinical resistance. This approach is expected to enable durable clinical responses across the range of RET alterations, with a favorable safety profile.

BLU-667 was discovered by Blueprint Medicines’ research team based on its proprietary compound library. The company is developing BLU-667 for the treatment of people with RET-altered NSCLC, MTC and other solid tumors. Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of BLU-667 and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for BLU-667 in the rest of the world.

On October 6, 2018 Loxo Oncology, Inc. (Nasdaq: LOXO), a biopharmaceutical company developing highly selective medicines for patients with genomically defined cancers, reported updated interim clinical data for LOXO-292 from the global Phase 1/2 LIBRETTO-001 trial in patients with RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer who were initially included in the LOXO-292 presentation at the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Loxo Oncology, OCT 6, 2018, View Source [SID1234529804]). In these 38 patients, approximately 3.5 months of additional patient follow-up were available, as were first follow-up scans for the nine patients most recently enrolled. Sixteen of 17 (94%) responding RET-mutant MTC patients remained on therapy, with median follow-up of 8.4 months. Seven of seven (100%) responding RET fusion-positive thyroid cancer patients remained on therapy, with median follow-up of 8.5 months. Inclusion of new restaging data for the most recently enrolled patients resulted in a 59% overall response rate (56% confirmed overall response rate) in the presented subset of RET-mutant MTC patients, and a 78% confirmed overall response rate in the presented subset of RET fusion-positive thyroid cancer patients. These data are being presented today at the 88th Annual Meeting of the American Thyroid Association.

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"I am very pleased to present the latest LOXO-292 clinical data to colleagues at ATA, demonstrating the activity and safety profile of this promising new agent for RET-altered thyroid cancers," said Lori J. Wirth, M.D., associate professor of medicine at Harvard Medical School and Massachusetts General Hospital. "In the months since ASCO (Free ASCO Whitepaper) we continue to see encouraging early evidence that LOXO-292 has the potential to provide durable responses in heavily pre-treated patients with RET-driven cancers, with a promising safety profile at the Phase 2 dose of 160 mg BID. RET has been a known oncogene in thyroid cancer for many years and I am hopeful that these LOXO-292 data can further increase the awareness of this important target and, with Breakthrough Therapy Designation in hand, that the clinical program will quickly advance to reach our patients in need. "

Trial Background

LIBRETTO-001 is a Phase 1/2 trial of LOXO-292 in advanced cancer patients who primarily have activating RET alterations. LIBRETTO-001 contains a Phase 1 dose escalation phase and a Phase 2 dose expansion phase. The primary endpoint of the Phase 1 is the determination of the maximum tolerated dose (MTD) or recommended dose for further study. Secondary endpoints include safety, overall response rate (by RECIST 1.1) and duration of response. Initial clinical data were first reported at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

Key Data Presented

The data presented today were based on a July 19, 2018 data cut-off date and included the 29 patients with RET-mutant MTC and the nine patients with RET fusion-positive thyroid cancer who were initially included in the LOXO-292 presentation at the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting.

Patients were heavily pretreated, having received a median of three prior systemic treatment regimens. Of the patients with RET-mutant MTC, 79% had previously received cabozantinib or vandetanib and 45% had received prior treatment with both agents. Of the patients with RET fusion-positive thyroid cancer, 78% had previously received radioactive iodine and 78% had previously received sorafenib or lenvatinib.

With 3.5 months of additional follow-up since the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting presentation, LOXO-292 demonstrated encouraging, early evidence of durable activity. Sixteen of 17 (94%) responding RET-mutant MTC patients remained on therapy and in response (median follow-up of 7.6 months for all 29 patients; median follow-up of 8.4 months for responding patients). Seven of seven (100%) responding RET fusion-positive thyroid remained on therapy and in response (median follow-up of 7.6 months for all nine patients; median follow-up of 8.5 months for responding patients). The longest treated patient was the first RET-mutant MTC patient enrolled, who had been on therapy for more than 13 months as of the data cut-off date.

The new data cutoff date allowed for the inclusion of first follow-up scans for nine patients (seven with RET-mutant MTC and two with RET fusion-positive thyroid cancer) who had not had any post-baseline response assessment as of the ASCO (Free ASCO Whitepaper) presentation. Of 29 patients with RET-mutant MTC, 17 demonstrated an objective response by RECIST 1.1 (two complete responses and 15 partial responses, including two patients with unconfirmed partial responses awaiting confirmatory response assessments) and seven additional patients demonstrated evidence of tumor regression (-12% to -26%). The overall response rate was 59% (17/29) (95% CI: 39%-77%) and the confirmed overall response rate was 56% (15/27) (95% CI: 35%-75%). Included in this analysis are two patients with non-measurable disease at baseline (1 confirmed complete response, 1 stable disease). Of nine patients with RET fusion-positive thyroid cancer, seven demonstrated an objective response by RECIST 1.1 (all partial responses) and one additional patient demonstrated evidence of tumor regression (-21%). The confirmed overall response rate was 78% (7/9) (95% CI: 40%-97%). Included in the analysis is one patient with non-measurable disease at baseline (stable disease). Response assessments were performed by the local clinical trial sites.

Anti-tumor activity was observed regardless of RET mutation, RET fusion partner, and prior multikinase inhibitor treatment. One patient, with RET fusion-positive thyroid cancer, had RECIST target lesions in the central nervous system (CNS) and exhibited an intracranial partial response by RECIST 1.1, pending confirmation.

Of the 82 patients in the safety analysis, most treatment-emergent adverse events were Grade 1 in severity and judged by the investigator as not related to LOXO-292. The treatment-emergent adverse events observed in ≥10% of patients, regardless of relationship to LOXO-292, were diarrhea (15% Grade 1, 7% Grade 2, 1% Grade 3), fatigue (9% Grade 1, 13% Grade 2, 0% ≥Grade 3), dry mouth (21% Grade 1, 0% ≥Grade 2), constipation (17% Grade 1, 2% Grade 2, 0% ≥Grade 3), hypomagnesemia (12% Grade 1, 1% Grade 2, 0% ≥Grade 3), cough (11% Grade 1, 1% Grade 2, 0% ≥Grade 3), headache (10% Grade 1, 1% Grade 2, 1% Grade 3) and nausea (9% Grade 1, 4% Grade 2, 0% ≥Grade 3). Four patients experienced adverse events ≥Grade 3 that were attributed to LOXO-292 (all Grade 3): tumor lysis syndrome, increased ALT/AST, diarrhea, and thrombocytopenia. All resolved with dose interruption. 160mg BID has been advanced as the Phase 2 dose, with dose exploration at 200mg BID ongoing to further characterize LOXO-292 safety and efficacy.

The presentation will be available online at View Source

About LOXO-292
LOXO-292 is an oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. RET fusions and mutations occur across multiple tumor types with varying frequency. LOXO-292 was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach. LOXO-292 has been granted Breakthrough Therapy Designation by the U.S. FDA.

LOXO-292 is currently being studied in the global LIBRETTO-001 Phase 1/2 trial. For additional information about the LOXO-292 clinical trial, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient RET Clinical Trial Hotline at 1-855-RET-4-292 or email [email protected].

About RET-Altered Cancers
Genomic alterations in RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. RET fusions have been identified in approximately 2% of non-small cell lung cancer, 10-20% of papillary and other thyroid cancers, and a subset of other cancers. Activating RET point mutations account for approximately 60% of medullary thyroid cancer (MTC). Both RET fusion cancers and RET-mutant MTC are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as "oncogene addiction," renders such tumors highly susceptible to small molecule inhibitors targeting RET.

On October 5, 2018 The U.S. Food and Drug Administration reported a supplemental application for Gardasil 9 (Human Papillomavirus (HPV) 9-valent Vaccine, Recombinant) expanding the approved use of the vaccine to include women and men aged 27 through 45 years (Press release, US FDA, OCT 5, 2018, View Source,aged%2027%20through%2045%20years. [SID1234607430]). Gardasil 9 prevents certain cancers and diseases caused by the nine HPV types covered by the vaccine.

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"Today’s approval represents an important opportunity to help prevent HPV-related diseases and cancers in a broader age range," said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. "The Centers for Disease Control and Prevention has stated that HPV vaccination prior to becoming infected with the HPV types covered by the vaccine has the potential to prevent more than 90 percent of these cancers, or 31,200 cases every year, from ever developing."

According to the CDC, every year about 14 million Americans become infected with HPV; about 12,000 women are diagnosed with and about 4,000 women die from cervical cancer caused by certain HPV viruses. Additionally, HPV viruses are associated with several other forms of cancer affecting men and women.

Gardasil, a vaccine approved by the FDA in 2006 to prevent certain cancers and diseases caused by four HPV types, is no longer distributed in the U.S. In 2014, the FDA approved Gardasil 9, which covers the same four HPV types as Gardasil, as well as an additional five HPV types. Gardasil 9 was approved for use in males and females aged 9 through 26 years.

The effectiveness of Gardasil is relevant to Gardasil 9 since the vaccines are manufactured similarly and cover four of the same HPV types. In a study in approximately 3,200 women 27 through 45 years of age, followed for an average of 3.5 years, Gardasil was 88 percent effective in the prevention of a combined endpoint of persistent infection, genital warts, vulvar and vaginal precancerous lesions, cervical precancerous lesions, and cervical cancer related to HPV types covered by the vaccine. The FDA’s approval of Gardasil 9 in women 27 through 45 years of age is based on these results and new data on long term follow-up from this study.

Effectiveness of Gardasil 9 in men 27 through 45 years of age is inferred from the data described above in women 27 through 45 years of age, as well as efficacy data from Gardasil in younger men (16 through 26 years of age) and immunogenicity data from a clinical trial in which 150 men, 27 through 45 years of age, received a 3-dose regimen of Gardasil over 6 months.

The safety of Gardasil 9 was evaluated in about a total of 13,000 males and females. The most commonly reported adverse reactions were injection site pain, swelling, redness and headaches.

The FDA granted the Gardasil 9 application priority review status. This program facilitates and expedites the review of medical products that address a serious or life-threatening condition.

The FDA granted approval of this supplement to the Gardasil 9 Biologics License Application to Merck, Sharp & Dohme Corp. a subsidiary of Merck & Co., Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

On October 5, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has accepted for filing with Priority Review its New Drug Application (NDA) seeking accelerated approval for selinexor, its first in class, oral SINE compound, as a new treatment for patients with penta-refractory multiple myeloma (Press release, Karyopharm, OCT 5, 2018, View Source [SID1234529861]). The FDA also granted Karyopharm’s request for Priority Review and assigned an action date of April 6, 2019 under the Prescription Drug User-Fee Act (PDUFA). In its acceptance letter, the FDA has stated that it is currently planning to hold an advisory committee meeting to discuss this application.

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"As a potential new therapy with a novel mechanism and compelling clinical profile, we believe oral selinexor, if approved, will provide a meaningful therapeutic option for patients battling highly resistant, penta-refractory myeloma," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "The acceptance of this NDA for review and grant of Priority Review mark significant milestones for the selinexor program, and further underscores the high level of unmet need in this patient population. We look forward to working with the FDA during the review process."

Provided marketing approval is granted by the FDA, Karyopharm plans to commercialize selinexor in the U.S. as early as the first half of 2019. The Company also plans to submit a Marketing Authorization Application to the European Medicines Agency in early 2019 with a request for conditional approval.

Priority Review is granted by the FDA to drugs that, if approved, would provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious condition when compared to standard applications. Selinexor has received both Orphan Drug and Fast Track designations from the FDA for the treatment for patients with penta-refractory multiple myeloma.

About Selinexor

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,600 patients have been treated with selinexor. In April and September 2018, Karyopharm reported positive top-line data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with penta-refractory multiple myeloma. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm’s New Drug Application (NDA) has been accepted for filing and granted Priority Review by the FDA, and oral selinexor is currently under review by the FDA as a possible new treatment for patients with penta-refractory multiple myeloma. The Company also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in early 2019 with a request for conditional approval. Selinexor is also being evaluated in several other mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), as a potential backbone therapy in combination with approved therapies (STOMP), in diffuse large B-cell lymphoma (SADAL), liposarcoma (SEAL), and an investigator-sponsored study 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.

Further Information About Potential Accelerated Approval for Selinexor in Multiple Myeloma

The FDA instituted its Accelerated Approval Program to allow for expedited approval of drugs that treat serious conditions and that fill an unmet medical need based on a surrogate endpoint or an intermediate clinical endpoint thought to predict clinical benefit, like overall response rate (ORR). Accelerated approval is available only for drugs that provide a meaningful therapeutic benefit over existing treatments at the time of consideration of the application for accelerated approval, which the FDA has reiterated in its feedback to the Company. Particularly in disease areas with multiple available and potential new therapies, such as multiple myeloma, accelerated approval carries a high regulatory threshold. Consistent with its general guidance, the FDA has noted to the Company its preference for randomized studies geared toward full approval, which the Company has undertaken with the ongoing pivotal, Phase 3 BOSTON study, and has reminded the Company that accelerated approval requires patients to have exhausted all available approved therapies. FDA’s Fast Track designation is available to therapeutics treating an unmet medical need in a serious condition; the Company has received Fast Track designation from the FDA specifically for the population treated in the STORM trial. In light of this recognition that the STORM patient population represents an unmet medical need and the positive top-line data reported in April and September 2018, the Company believes that the STORM study should support its request to the FDA for accelerated approval.