-- 95 percent confirmed wide effect complaint and 37 percent confirmed implicit remission complaint successful treatment-naïve patients with SM-AHN, the astir communal subtype of precocious SM, successful PATHFINDER proceedings of AYVAKIT® (avapritinib) --
-- Ongoing endurance benefits, with up to six years of follow-up, successful patients with precocious SM from EXPLORER proceedings of AYVAKIT --
-- Top-line, 12-week Part 1 information from HARBOR proceedings amusement elenestinib (BLU-263) improved measures of mast compartment load and patient-reported symptoms successful indolent SM --
CAMBRIDGE, Mass., Dec. 11, 2022 /PRNewswire/ -- Blueprint Medicines Corporation (NASDAQ: BPMC) contiguous announced AYVAKIT® (avapritinib) information showing high, durable effect rates and prolonged wide endurance (OS) successful patients with precocious systemic mastocytosis (Advanced SM), including SM with an associated hematological neoplasm (SM-AHN). The findings are being reported successful 2 presentations, including an oral presumption featuring updated follow-up from treatment-naïve patients successful the PATHFINDER trial, astatine the 64th American Society of Hematology (ASH) Annual Meeting and Exposition successful New Orleans. AYVAKIT is approved by the U.S. Food and Drug Administration (FDA) for the attraction of adults with Advanced SM.
SM is simply a uncommon hematologic upset driven by the KIT D816V mutation successful astir 95 percent of cases. In precocious SM, the median OS has ranged from little than six months to astir 3.5 years, depending connected the subtype.1 AYVAKIT was designed to potently and selectively inhibit D816V mutant KIT.
"AYVAKIT has demonstrated important objective benefits successful patients with precocious systemic mastocytosis, including implicit remissions and durable responses that person translated into a highly meaningful interaction connected wide survival," said Deepti Radia, M.D., a hematologist and an researcher connected the PATHFINDER and EXPLORER trials. "As a doc specializing successful SM and different myeloproliferative neoplasms, I americium encouraged that treatment-naïve patients with SM-AHN had a 95 percent effect complaint and an estimated two-year endurance complaint of 86 percent successful the PATHFINDER trial. Before the instauration of KIT D816V-targeted therapy, physicians often focused connected treating the AHN constituent of SM-AHN. AYVAKIT represents a practice-changing advancement for this diligent population, and updated PATHFINDER information item the value of treating the SM for aboriginal therapeutic involution successful SM-AHN patients with measurable 'C' findings, excluding those with assertive AHNs."
"AYVAKIT has go the modular of attraction care for precocious systemic mastocytosis successful the U.S., with a increasing fig of patients receiving the therapy aboriginal successful the people of their disease. This presumption is further reinforced by updated AYVAKIT results successful the treatment-naïve setting, which see wide response, implicit remission and endurance rates that found a caller benchmark for patients with precocious SM," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "Through our semipermanent concern with the SM community, we person amassed datasets reflecting hundreds of diligent years of objective acquisition crossed precocious and non-advanced forms of the disease. This breadth of information highlights beardown objective execution and reflects our enactment successful processing a portfolio of targeted attraction options designed to code the aesculapian needs of patients with SM."
AYVAKIT – Updated information from the PATHFINDER and EXPLORER trials successful precocious SM
Long-term follow-up of 38 treatment-naïve patients from the PATHFINDER proceedings and 69 patients from the EXPLORER proceedings – careless of enactment of therapy – further validate the objective efficacy and information illustration of AYVAKIT successful precocious SM. Based connected modified IWG-MRT-ECNM criteria, the wide effect complaint (ORR) was defined arsenic implicit remission with afloat oregon partial betterment of peripheral humor counts (CR/CRh), partial remission oregon objective improvement. All responses were confirmed.
In the PATHFINDER trial, AYVAKIT showed wide objective enactment successful treatment-naïve patients evaluable for effect (n=25), including those with SM-AHN (n=19), arsenic of a information cutoff day of April 20, 2021.
For treatment-naïve patients crossed precocious SM subtypes:
- ORR was 84 percent and CR/CRh complaint was 32 percent.
- Median clip to effect was 2 months and median clip to CR/CRh was six months.
- Median duration of effect (DOR) has not been reached.
- Estimated 24-month OS complaint was 88 percent.
For treatment-naïve patients with SM-AHN:
- ORR was 95 percent and CR/CRh complaint was 37 percent.
- Estimated 24-month OS complaint was 86 percent.
In addition, improvements were observed crossed hematologic parameters, specified arsenic monocytes and eosinophils successful the peripheral blood, suggesting multi-lineage engagement of the KIT D816V mutation.
In the EXPLORER trial, 57 patients crossed lines of therapy were evaluable for effect arsenic of a information cutoff day of April 5, 2022. The ORR was 77 percent, with median DOR and OS not reached successful patients followed for up for six years.
Safety information from the PATHFINDER and EXPLORER trials were accordant with antecedently reported results and the FDA approved labeling for AYVAKIT, and reenforce the favorable benefit-risk illustration of AYVAKIT astatine the 200 mg once-daily (QD) recommended dose. The astir communal treatment-related adverse events (AEs) included periorbital edema, thrombocytopenia, peripheral edema, anemia and nausea. Discontinuations owed to treatment-related AEs occurred successful 4 treatment-naïve patients (11 percent) since the initiation of the PATHFINDER proceedings successful 2018, and 7 patients crossed lines of therapy (10 percent) since the initiation of the EXPLORER proceedings successful 2016.
Copies of Blueprint Medicines information presentations from the ASH yearly gathering are disposable successful the "Science—Publications and Presentations" conception of the company's website astatine www.BlueprintMedicines.com.
Elenestinib (BLU-263) – Top-line results from Part 1 of HARBOR proceedings successful indolent SM
In addition, Blueprint Medicines contiguous announced top-line, 12-week results from the dose-finding Part 1 of the HARBOR proceedings of elenestinib, a next-generation KIT D816V inhibitor, reflecting the company's semipermanent committedness to SM. HARBOR Part 1 was designed to measure concurrent dose cohorts of elenestinib positive champion disposable therapy (elenestinib group) versus placebo positive champion disposable therapy (placebo group) successful patients with indolent SM. The proceedings included 29 patients successful the elenestinib radical (n=10 astatine 25 mg QD; n=10 astatine 50 mg QD; n=9 astatine 100 mg QD), and 10 patients successful the placebo group.
Elenestinib showed grounds of objective enactment and information accordant with its preclinical illustration and a completed Phase 1 steadfast unpaid trial. Elenestinib attraction led to accelerated improvements successful nonsubjective measures of mast compartment burden, including serum tryptase and KIT D816V allele fraction, and full grounds people (TSS) arsenic measured by the Indolent SM Symptom Assessment Form (ISM-SAF). At 12 weeks, elenestinib demonstrated akin reductions successful TSS crossed dose cohorts. In addition, accordant with antecedently reported information from the PIONEER proceedings of AYVAKIT successful indolent SM, alteration successful serum tryptase was not correlated with alteration successful TSS. Safety results amusement that elenestinib was mostly well-tolerated, and determination were nary discontinuations owed to AEs. Blueprint Medicines plans to contiguous information from Part 1 of the HARBOR proceedings astatine a aesculapian legislature successful 2023.
About AYVAKIT (avapritinib)
AYVAKIT (avapritinib) is simply a kinase inhibitor approved by the FDA for the attraction of adults with Advanced SM, including assertive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast compartment leukemia (MCL), and adults with unresectable oregon metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. For much information, visit AYVAKIT.com. This medicine is approved in Europe (AYVAKYT®) for the attraction of adults with ASM, SM-AHN oregon MCL, aft astatine slightest 1 systemic therapy, and adults with unresectable oregon metastatic GIST harboring the PDGFRA D842V mutation. Please click present to spot the full U.S. Prescribing Information for AYVAKIT, and click present to spot the European Summary of Product Characteristics for AYVAKYT. AYVAKIT/AYVAKYT is not approved for the attraction of immoderate different denotation successful the U.S. or Europe.
To larn astir ongoing oregon planned objective trials, contact Blueprint Medicines astatine [email protected] oregon 1-888-BLU-PRNT (1-888-258-7768). Additional accusation is disposable astatine blueprintclinicaltrials.com oregon clinicaltrials.gov.
Important Safety Information
Serious intracranial hemorrhage (ICH) whitethorn hap with AYVAKIT treatment; fatal events occurred successful <1% of patients. Overall, ICH (eg, subdural hematoma, ICH, and cerebral hemorrhage) occurred successful 2.9% of 749 patients who received AYVAKIT. In Advanced SM patients who received AYVAKIT astatine 200 mg daily, ICH occurred successful 2 of 75 patients (2.7%) who had platelet counts ≥50 x 109/L anterior to initiation of therapy and successful 3 of 80 patients (3.8%) careless of platelet counts. Monitor patients intimately for hazard of ICH including those with thrombocytopenia, vascular aneurysm oregon a past of ICH oregon cerebrovascular mishap wrong the anterior year. Permanently discontinue AYVAKIT if ICH of immoderate people occurs. A platelet number indispensable beryllium performed anterior to initiating therapy. AYVAKIT is not recommended successful Advanced SM patients with platelet counts <50 x 109/L. Following attraction initiation, platelet counts indispensable beryllium performed each 2 weeks for the archetypal 8 weeks. After 8 weeks of treatment, show platelet counts each 2 weeks oregon arsenic clinically indicated based connected platelet counts. Manage platelet counts of <50 x 109/L by attraction interruption oregon dose reduction.
Cognitive adverse reactions tin hap successful patients receiving AYVAKIT. Cognitive adverse reactions occurred successful 39% of 749 patients and successful 28% of 148 SM patients (3% were Grade >3). Memory impairment occurred successful 16% of patients; each events were Grade 1 oregon 2. Cognitive upset occurred successful 10% of patients; <1% of these events were Grade 3. Confusional authorities occurred successful 6% of patients; <1% of these events were Grade 3. Other events occurred successful <2% of patients. Depending connected the severity, withhold AYVAKIT and past resume astatine aforesaid dose oregon astatine a reduced dose upon improvement, oregon permanently discontinue.
AYVAKIT tin origin fetal harm erstwhile administered to a large woman. Advise large women of the imaginable hazard to a fetus. Advise females and males of reproductive imaginable to usage an effectual method of contraception during attraction with AYVAKIT and for 6 weeks aft the last dose of AYVAKIT. Advise women not to breastfeed during attraction with AYVAKIT and for 2 weeks aft the last dose.
The astir communal adverse reactions (≥20%) astatine each doses were edema, diarrhea, nausea, and fatigue/asthenia.
Avoid coadministration of AYVAKIT with beardown and mean CYP3A inhibitors. If coadministration with a mean CYP3A inhibitor cannot beryllium avoided, trim dose of AYVAKIT. Avoid coadministration of AYVAKIT with beardown and mean CYP3A inducers.
To study suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 oregon FDA astatine 1-800-FDA-1088 or www.fda.gov/medwatch.
Please click present to spot the full Prescribing Information for AYVAKIT.
About Systemic Mastocytosis
Systemic mastocytosis (SM) is simply a uncommon illness chiefly driven by the KIT D816V mutation. Uncontrolled proliferation and activation of mast cells effect successful chronic, terrible and often unpredictable symptoms crossed aggregate organ systems. The immense bulk of those affected person non-advanced (indolent oregon smoldering) SM. A wide scope of symptoms, including anaphylaxis, maculopapular rash, pruritis, diarrhea, encephalon fog, fatigue and bony pain, often persist successful patients with non-advanced SM contempt attraction with aggregate symptom-directed therapies. This load of illness tin pb to a profound, antagonistic interaction connected prime of life. Patients often unrecorded successful fearfulness of severe, unexpected symptoms, person constricted quality to enactment oregon execute regular activities, and isolate themselves to support against unpredictable triggers. Currently, determination are nary approved therapies for the attraction of non-advanced SM.
A number of patients person precocious SM, which encompasses a radical of high-risk SM subtypes including ASM, SM-AHN and MCL. In summation to mast compartment activation symptoms, precocious SM is associated with organ harm owed to mast compartment infiltration and mediocre survival.
About Blueprint Medicines
Blueprint Medicines is a planetary precision therapy institution that invents life-changing therapies for radical with crab and humor disorders. Applying an attack that is some precise and agile, we make medicines that selectively people familial drivers, with the extremity of staying 1 measurement up crossed stages of disease. Since 2011, we person leveraged our probe platform, including expertise successful molecular targeting and world-class cause plan capabilities, to rapidly and reproducibly construe our technological innovation into a wide pipeline of important approved and investigational precision therapies aimed astatine addressing difficult-to-treat cancers and humor disorders. Today, we are delivering our approved medicines to patients in the United States, Europe, and successful different geographies ourselves oregon done our partners. In addition, we are globally advancing aggregate programs for systemic mastocytosis, lung cancer, bosom cancer, and different genomically defined cancers, and crab immunotherapy. For much information, visit www.BlueprintMedicines.com and travel america on Twitter (@BlueprintMeds) and LinkedIn.
Cautionary Note Regarding Forward-Looking Statements
This property merchandise contains forward-looking statements wrong the meaning of the Private Securities Litigation Reform Act of 1995, arsenic amended, including, without limitation, statements regarding expectations regarding the imaginable benefits of AYVAKIT for the attraction of patients with SM; statements regarding plans and expectations for Blueprint Medicines' existent oregon aboriginal approved drugs and cause candidates; and Blueprint Medicines' strategy, goals and anticipated milestones, concern plans and focus. The words "aim," "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target" and akin expressions are intended to place forward-looking statements, though not each forward-looking statements incorporate these identifying words. Any forward-looking statements successful this property merchandise are based connected management's existent expectations and beliefs and are taxable to a fig of risks, uncertainties and important factors that whitethorn origin existent events oregon results to disagree materially from those expressed oregon implied by immoderate forward-looking statements contained successful this property release, including, without limitation, risks and uncertainties related to the interaction of the COVID-19 pandemic to Blueprint Medicines' business, operations, strategy, goals and anticipated milestones, including Blueprint Medicines' ongoing and planned probe and find activities, quality to behaviour ongoing and planned objective trials, objective proviso of existent oregon aboriginal cause candidates, commercialized proviso of existent oregon aboriginal approved products, and launching, selling and selling existent oregon aboriginal approved products; Blueprint Medicines' quality and plans successful continuing to found and grow a commercialized infrastructure, and successfully launching, selling and selling existent oregon aboriginal approved products; Blueprint Medicines' quality to successfully grow the approved indications for AYVAKIT/AYVAKYT and GAVRETO® (pralsetinib) oregon get selling support for AYVAKIT/AYVAKYT successful further geographies successful the future; the hold of immoderate existent oregon planned objective trials oregon the improvement of Blueprint Medicines' existent oregon aboriginal cause candidates; Blueprint Medicines' advancement of aggregate early-stage efforts; Blueprint Medicines' quality to successfully show the information and efficacy of its cause candidates and summation support of its cause candidates connected a timely basis, if astatine all; the preclinical and objective results for Blueprint Medicines' cause candidates, which whitethorn not enactment further improvement of specified cause candidates either arsenic monotherapies oregon successful operation with different agents oregon whitethorn interaction the anticipated timing of information oregon regulatory submissions; the timing of the initiation of objective trials and proceedings cohorts astatine objective proceedings sites and diligent enrollment rates; actions of regulatory agencies, which whitethorn impact the initiation, timing and advancement of objective trials; Blueprint Medicines' quality to obtain, support and enforce patent and different intelligence spot extortion for AYVAKIT/AYVAKYT oregon immoderate cause candidates it is developing; Blueprint Medicines' quality to make and commercialize companion diagnostic tests for AYVAKIT/AYVAKYT oregon immoderate of its existent and aboriginal cause candidates; Blueprint Medicines' quality to successfully grow its operations, probe level and portfolio of therapeutic candidates, and the timing and costs thereof; Blueprint Medicines' quality to recognize the anticipated benefits of its enforcement enactment modulation plan; and the occurrence of Blueprint Medicines' existent and aboriginal collaborations, financing arrangements, partnerships oregon licensing arrangements. These and different risks and uncertainties are described successful greater item successful the conception entitled "Risk Factors" successful Blueprint Medicines' filings with the Securities and Exchange Commission (SEC), including Blueprint Medicines' astir caller Annual Report connected Form 10-K, arsenic supplemented by its astir caller Quarterly Report connected Form 10-Q and immoderate different filings that Blueprint Medicines has made oregon whitethorn marque with the SEC successful the future. Any forward-looking statements contained successful this property merchandise correspond Blueprint Medicines' views lone arsenic of the day hereof and should not beryllium relied upon arsenic representing its views arsenic of immoderate consequent date. Except arsenic required by law, Blueprint Medicines explicitly disclaims immoderate work to update immoderate forward-looking statements.
Reference
1 Sperr WR, Kundi M, Alvarez-Twose I, et al. International prognostic scoring strategy for mastocytosis (IPSM): a retrospective cohort study. Lancet Haematol. 2019;6(12):e638-e649.
Trademarks
Blueprint Medicines, AYVAKIT, AYVAKYT, GAVRETO and associated logos are trademarks of Blueprint Medicines Corporation.
SOURCE Blueprint Medicines Corporation
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