Dasynoc (dasatinib amorphous) / Xspray Pharma - LARVOL DELTA

FDA sets PDUFA-date for Xspray Pharma’s re-submitted application for Dasynoc (Xspray Pharma Press Release) - "The U.S. Food and Drug Administration (FDA) has acknowledged receipt of Xspray Pharma's re-submitted NDA (New Drug Application) for Dasynoc. The re-submission is based on a CRL (Complete Response Letter) received from the FDA in July 2024 where additional information was requested. The FDA has now set the PDUFA date to 7 October 2025, which is the FDA's deadline for communicating its decision on the company's application. Xspray Pharma is now continuing to prepare for the US launch of Dasynoc with the aim that it can begin as soon as possible if market approval is received in October."

FDA filing • PDUFA • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia

Xspray Pharma re-submits its FDA application (Xspray Pharma Press Release) - "Xspray Pharma AB (publ) has re-submitted its application for market approval for Dasynoc, the company's lead product candidate, an amorphous dasatinib for the treatment of leukemia. The application procedure thus runs according to the most recently communicated plan. Within 2-4 weeks, the FDA is expected to announce a new PDUFA date, i.e. the date they intend to decide on the application."

FDA filing • Chronic Myeloid Leukemia • T Acute Lymphoblastic Leukemia

Xspray backs down after delayed FDA application [Google translation] (BioStock) - "The submission of Xspray Pharma's updated FDA application for Dasynoc is postponed to March/April 2025. The company had previously planned to submit the application in late 2024, but after a deviating tablet batch and production lead times, the timeline is now being adjusted. The stock is falling on the news....The company has been working on the FDA application for the drug candidate for some time and received a Complete Response Letter from the agency last year. The FDA requested additional information regarding the drug's labeling and what emerged during an inspection of the production facility....The stock market responds negatively to the news by trading the stock down by approximately 17 percent."

FDA filing • Stock price • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia

Scientific Article in Leading Journal Endorses Xspray Pharma’s HyNap Technology (Businesswire) - "A new scientific article, published in the US journal Clinical Pharmacology in Drug Development, shows how Xspray Pharma's HyNap technology improves the bioavailability and reduces variability of two important tyrosine kinase inhibitors (TKIs), Dasynoc (XS004, dasatinib) and XS005 (sorafenib)....Dasynoc (XS004, dasatinib): Bioequivalence at 30% lower dose, with up to 4.8 times less variation in plasma exposure compared to the reference product. XS005 (sorafenib): 45% increase in absorption and up to 2.8 times less variability in plasma exposure compared to the reference product."

Clinical • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Oncology

Xspray Pharma Announces Positive FDA Meeting and Plans for Dasynoc NDA Resubmission (Businesswire) - "Xspray Pharma AB...today announced significant progress following a productive meeting with the U.S. Food and Drug Administration (FDA). The company plans to resubmit its New Drug Application (NDA) for Dasynoc in Q4 2024, incorporating feedback from the Complete Response Letter (CRL) issued by FDA in July 2024. If the FDA sets a two-month review period upon resubmission, the launch of Dasynoc could be expected as early as Q1 2025....Upon resubmission, Xspray Pharma expects the FDA to assign a new Prescription Drug User Fee Act (PDUFA) date, with a final decision anticipated within two or six months of the resubmission, depending on the review timeline set by the FDA."

FDA filing • Launch US • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Oncology

Interim Report Second Quarter 2024 (Xspray Pharma Press Release) - "Xspray Pharma announced the outcome of the exercised warrants of series TO6. In total, 2,508,723 warrants of series TO6, corresponding to approximately 80 percent, were exercised to subscribe for the same number of new shares...Proceeds will be used for the US launch of the company's first product, Dasynoc...The launch of Dasynoc will not be possible in September, but rather we will need to wait for an additional time period...we have decided to temporarily pause our launch preparations for Dasynoc..."

Commercial • Launch US • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia

Xspray Pharma Shares New Information on Dasynoc, a Novel CML Treatment in Development (Xspray Pharma Press Release) - "Xspray Pharma AB...has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding the New Drug Application (NDA) for Dasynoc, a novel treatment for chronic myeloid leukemia (CML) and acute lymphocytic leukemia (ALL). The updated NDA was sent to the FDA on January 31, 2024. In the CRL the FDA requests additional information pertaining to the labeling comprehension and the pre-approval inspection at the third party’s manufacturing site, which was conducted 10 to 19 of June, 2024. Importantly, the FDA does not request additional clinical studies, nor does it question any submitted stability or clinical data."

CRL • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia

XS004 Dasatinib (XS004) Improves Variability and Bioavailability in Humans Using Amorphous Solid Dispersion Formulation of Dasatinib With Potential Implications for Its Clinical Use (SOHO 2024) - "XS004 displayed more robust and consistent GI absorption and bioavailability, with significantly reduced intra- and inter-individual variability in plasma dasatinib concentrations, compared to the original crystalline dasatinib. The solubility of dasatinib-ASD was substantially less pH-dependent at GI-relevant pH values. The results suggest that XS004 reduces the risk of both low exposure and high exposure outliers, with lower risk of exposure outside the therapeutic window."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Bristol Myers’ leukemia blockbuster set to face generic rivals (BioPharma Dive) - "Bristol Myers Squibb, for one, could soon hit headwinds for its blockbuster Sprycel as the first generic of the leukemia drug is expected to hit the market in September....The tablet has been a reliable blockbuster for Bristol Myers over the years, reaching $1.9 billion in global sales in 2023. Sales topped $2.1 billion in both 2022 and 2021....Bristol Myers settled with XSpray last year, clearing the way for the challenger to launch a generic dasatinib as soon as Sept. 1, 2024. XSpray has an FDA decision date of July 31 for its 'optimized version of dasatinib,' Dasynoc."

Generic launch • PDUFA • Sales • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Enhanced Bioavailability and Reduced Variability of Dasatinib and Sorafenib with a Novel Amorphous Solid Dispersion Technology Platform. (PubMed, Clin Pharmacol Drug Dev) - "The PKs of XS004 (dasatinib-ASD, 100 mg tablet) and XS005 (sorafenib-ASD, 2 × 50 mg capsules) were compared with their crystalline formulated reference drugs (140 mg of dasatinib-reference and 200 mg of sorafenib-reference). XS005 had an increased absorption and bioavailability of 45% and 2.2-2.8 times lower variability, respectively, but it was not bioequivalent at the investigated dose level. Taken together, the formulation platform is suited to generate improved PKI formulations with consistent bioavailability and a reduced pH-dependent absorption process."

Journal

Xspray Pharma Announces Fourth Product Candidate, targeting USD 2.3 billion Market (Xspray Pharma Press Release) - "Xspray Pharma AB announces the strategic decision to advance its fourth product candidate XS015 into clinical trials. The decision follows the successful scale-up of its innovative amorphous solid dispersion (ASD) formulation of the active substance cabozantinib, used in renal cell carcinoma and other cancers....Today’s announcement of the decision to advance the product candidate XS015 into clinical trials has been made possible by the successful scale-up of the company’s ASD-formulation of cabozantinib....Xspray is currently in the final phase of preparation for the anticipated launch of its first product, Dasynoc, on September 1, 2024 pending final FDA approval."

Commercial • Launch US • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

FDA Accepts Xspray Pharma’s NDA-resubmission for Dasynoc – PDUFA Date set to 31 July 2024 (Businesswire) - "Xspray Pharma AB...The U.S. Food and Drug Administration (FDA) has accepted the resubmission of Xspray Pharma’s New Drug Application (NDA) for Dasynoc, following a Complete Response Letter (CRL) where additional information was requested. The FDA has now assigned a Prescription Drug User Fee Act (PDUFA) date to 31st of July, 2024. This is the FDA’s deadline for completing the approval process, marking a significant milestone for Dasynoc, Xspray’s innovative protein kinase inhibitor (PKI) product candidate for CML treatment....With an established PDUFA date set to 31st of July, Xspray Pharma continues to strategically plan for the commercial launch of Dasynoc on September 1, 2024."

Launch US • NDA • PDUFA date • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Xspray Publication Demonstrates High Concomitant Proton Pump Inhibitor and Tyrosine Kinase inhibitor Use in Chronic Myeloid Leukemia Resulting in Risk of Increased Mortality Which May be Mitigated by DASYNOC. (Xspray Pharma Press Release) - P1 | N=17 | NCT05433896 | Sponsor: Xspray Pharma AB | "Xspray Pharma AB...announced that CML patients have a high incidence of concomitant PPI and TKI co-administration that increases the risk of mortality....Of these patients, 5-year survival was 79% as compared with 94% among non-PPI users, resulting in a 3.5-fold increased risk of death (Hazard Ratio, 3.5; 95% Confidence Interval, 2.1-5.3; p<0.0001)....The bioavailability of DASYNOC (XS004, amorphous (non-crystalline) dasatinib), developed through Xspray’s HyNap technology, was also presented in the publication. In healthy volunteers, neither the peak blood concentration nor the overall exposure of DASYNOC was affected by co-administration of the PPI, omeprazole; compared with DASYNOC administration alone."

P1 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Despite warnings, co-medication with proton pump inhibitors and dasatinib is common in chronic myeloid leukemia, but XS004, a novel oral dasatinib formulation, provides reduced pH-dependence, minimizing undesirable drug-drug interactions. (PubMed, Eur J Haematol) - "In conclusion, despite warnings, PPI co-medication is common among dasatinib-treated CML patients in a real-world setting. The new XS004 ASD formulation of dasatinib provided, in contrast to original crystalline dasatinib, superior pH independence with stable bioavailability, thereby minimizing drug-drug interactions. This may improve the long-term efficacy and tolerability of dasatinib in CML."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Xspray Pharma receives request for additional information concerning Dasynoc from FDA (Xspray Pharma Press Release) - "On July 10, Xspray Pharma received a Complete Response Letter ('CRL') relating to its Dasynoc New Drug Application ('NDA') for all six strengths (15 mg, 36 mg, 50 mg, 57 mg, 70 mg, and 100 mg) under review by FDA. In the CRL, the agency noted that the agency received Xspray’s amendment filed on January 10, 2023, which was a complete response to FDA’s prior action letter issued September 1, 2022....In the CRL, the FDA accepted Xspray’s proposed product name, Dasynoc, and did not identify any deficiencies with the stability or clinical data submitted in support of the NDA to date. The FDA, however, did request that Xspray provide additional information to doctors and users to avoid confusion about the proper dosing of Dasynoc."

FDA event • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Xspray Pharma Partners with EVERSANA for the U.S. Launch and Commercialization of its Lead Product, Dasynoc (XS004) for the Treatment of Chronic Myeloid Leukemia (CML) and Acute Lymphatic Leukemia (ALL) (PRNewswire) - "Xspray Pharma AB...has signed an agreement with EVERSANA^® to support the U.S. launch and commercialization of the company's first innovative cancer therapy Dasynoc for the treatment of chronic myeloid leukemia (CML) and acute lymphatic leukemia (ALL). While maintaining financial and strategic control, Xspray Pharma will grant EVERSANA exclusive commercialization access to support its Dasynoc launch, aimed at the second half of 2023....Under the agreement, EVERSANA will provide Xspray with a dedicated commercialization team with deep experience in the successful commercialization of cancer drugs including TKI-products. This agreement provides Xspray with access to EVERSANA's seasoned commercial leaders and allows for a short launch period while optimizing its launch budget....The U.S. launch of the product is planned for the second half of 2023, at which time the company expects to have obtained approval from the FDA."

Launch US • Licensing / partnership • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

XS004 Dasatinib (XS004) Improves Variability and Bioavailability in Humans Using Amorphous Solid Dispersion Formulation of Dasatinib with Potential Implications for Its Clinical Use (ASH 2022) - "The results suggest that XS004, an ASD formulation of dasatinib, with improved biopharmaceutical features, reduces the risk of both low exposure and high exposure outliers, with lower risk of exposure outside the therapeutic window. This would likely diminish the risk of adverse events and optimize the therapeutic efficacy of dasatinib in patients with CML."

Clinical • Chronic Myeloid Leukemia • Gastrointestinal Disorder • Hematological Malignancies • Leukemia • Oncology

Comedication of Proton Pump Inhibitors and Dasatinib Is Common in CML but XS004, a Novel Amorphous Solid Dispersion Formulation of Dasatinib, Provides Improved Uptake and Low pH-Dependency, Minimizing Unwanted Drug-Drug Interactions (ASH 2022) - "The plasma pharmacokinetics of XS004 dasatinib was, in contrast to the original non-ASD, pH-sensitive dasatinib formulation, not significantly affected by comedication with omeprazole. In the clinic, with its low pH-dependency and augmented intestinal absorption, XS004 dasatinib can provide an improved option for safely administering the often-needed comedication with PPIs, potentially improving long-term efficacy and tolerability of dasatinib in CML."

Chronic Myeloid Leukemia • Gastrointestinal Disorder • Hematological Malignancies • Leukemia • Oncology

Comparative Bioavailability of XS004 (Dasatinib) Formulation G and SPRYCEL® (Dasatinib) in Healthy, Adult Subjects Under Fasting Conditions (clinicaltrials.gov) - P1 | N=110 | Completed | Sponsor: Xspray Pharma AB

New P1 trial

Evaluating the Effects of Omeprazole on the Pharmacokinetics of XS004 (Dasatinib) Tablets in Healthy Adult Subjects Under Fasting Conditions (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: Xspray Pharma AB

New P1 trial