Xspray Pharma AB · NDA 217644

¢ yy U.S. FOOD & DRUG ADMINISTRATION NDA 217644 COMPLETE RESPONSE Xspray Pharma AB c/o Lachman Consultant Services, Inc. Attention: Jennifer Leaming Principal Consultant 1600 Stewart Avenue, Suite 604 Westbury, NY 11590 Dear Jennifer Leaming: Please refer to your new drug application (NDA) dated August 18, 2025, received August 18, 2025, and your amendments, submitted pursuant to for (9) (nilotinib) capsules. We have completed our review of this application, as amended, and have determined that we cannot approve this application in its present form. We have described our reasons for this action below and, where possible, our recommendations to address these issues. CLINICAL PHARMACOLOGY 1. The results from the pivotal bioequivalence study (Study XS003-11) and population PK (POP-PK) study (Study XS003-16) indicate that XS003 |") capsules have approximately 25% lower systemic exposure compared to Tasigna 200 mg under fasting conditions in both single-dose and steady-state evaluations. This reduced exposure may result in diminished clinical efficacy for the following patient populations for whom Tasigna 200 mg is a recommended dosage: ¢ Hepatic impairment: 200 mg twice daily for patients with newly diagnosed Philadelphia-chromosome positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) with any degree of hepatic impairment, and for patients with resistance/intolerance to prior therapy with severe hepatic impairment ¢ Strong CYP3A4 inhibitor coadministration: 200 mg once daily for patients with newly diagnosed Ph+ CML-CP receiving strong CYP3A4 inhibitors Therefore, XS003 [1 is not approvable as submitted. Using XS003 [™) to cover both the Tasigna 200 mg and 300 mg dose levels is not acceptable; each XS003 strength must correspond to a single Tasigna dose level. Reference ID: 5810235 NDA 217644 Page 2 PRODUCT QUALITY FACILITY INSPECTIONS 3. Following a Current Good Manufacturing Process (CGMP) inspection of , listed in this application, FDA conveyed deficiencies to the representative of the facility. The facility should provide satisfactory responses to these deficiencies to the FDA office indicated on FDA 483 prior to your complete response. The facility’s satisfactory responses are dependent on FDA’s determination that the facility has come into compliance with CGMP and may require re-inspection of the facility. The deficiencies identified during the inspection may not be specific to your application. Therefore, you should coordinate with the facility for timely resolution. Your complete response should include the date(s) of the facility’s response(s) to the FDA Form 483. Please refer to Compliance Program CP 7356.002 for guidance on post inspection activities. Following resolution of the CGMP inspection, FDA may need to conduct a pre-approval inspection (PAI) of the facility. Satisfactory outcomes of both the PAI and the CGMP surveillance inspections will be needed prior to an approval of the application. PRESCRIBING INFORMATION Submit draft labeling that is responsive to our electronic communication dated April 17, 2026. Prior to resubmitting the labeling, use the SRPI checklist to correct any formatting errors to ensure conformance with the format items in regulations and guidances. In addition, submit updated content of labeling [21 CFR 314.50(I)(1)(i)] in structured product labeling (SPL) format as described at FDA.gov.! 1 http:/Awww.fda.gov/Forlndustry/DataStandards/StructuredProductLabeling/default.htm U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov Reference ID: 5810235, NDA 217644 Page 3 To facilitate review of your submission, provide a highlighted or marked-up copy that shows all changes, as well as a clean Word version. The marked-up copy should include annotations that support any proposed changes. Your proposed Prescribing Information (PI) must conform to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57. As you develop your proposed PI, we encourage you to review the labeling review resources on the Prescription Drug Labeling Resources? and Pregnancy and Lactation Labeling Final Rule’ websites, which include: e The Final Rule (Physician Labeling Rule) on the content and format of the PI for human drug and biological products e The Final Rule (Pregnancy and Lactation Labeling Rule) on the content and format of information in the PI on pregnancy, lactation, and females and males of reproductive potential e Regulations and related guidance documents e Asample tool illustrating the format for Highlights and Contents, and e The Selected Requirements for Prescribing Information (SRPI) - a checklist of important format items from labeling regulations and guidances. e FDA's established pharmacologic class (EPC) text phrases for inclusion in the Highlights Indications and Usage heading. e Additional resources for the PI, patient labeling, and carton/container labeling. CARTON AND CONTAINER LABELING We reserve comment on the proposed labeling until the application is otherwise adequate. PROPRIETARY NAME Please refer to our correspondence dated February 19, 2026, which addresses the proposed proprietary name, 2). This name was found conditionally acceptable pending approval of the application in the current review cycle. Please resubmit the proposed proprietary name when you respond to all of the application deficiencies that have been identified in this letter. 2 https://www.fda.gov/drugs/laws-acts-and-rules/prescription-drug-labeling-resources 3 https://www.fda.gov/drugs/labeling-information-drug-products/pregnancy-and-lactation-labeling-drugs- final-rule U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov Reference ID: 5810235 NDA 217644 Page 4 SAFETY UPDATE When you respond to the above deficiencies, include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b). The safety update should include data from all nonclinical and clinical studies/trials of the drug under consideration regardless of indication, dosage form, or dose level. (1) Describe in detail any significant changes or findings in the safety profile. (2) When assembling the sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, incorporate new safety data as follows: e Present new safety data from the studies/clinical trials for the proposed indication using the same format as in the original submission. e Present tabulations of the new safety data combined with the original application data. e Include tables that compare frequencies of adverse events in the original application with the retabulated frequencies described in the bullet above. e For indications other than the proposed indication, provide separate tables for the requencies of adverse events occurring in clinical trials. (3) Present a retabulation of the reasons for premature trial discontinuation by incorporating the drop-outs from the newly completed trials. Describe any new trends or patterns identified. (4) Provide case report forms and narrative summaries for each subject who died during a Clinical trial or who did not complete a trial because of an adverse event. In addition, provide narrative summaries for serious adverse events. (5) Describe any information that suggests a substantial change in the incidence of common, but less serious, adverse events between the new data and the original application data. (6) Provide updated exposure information for the clinical studies/trials (e.g., number of subjects, person time). (7) Provide a summary of worldwide experience on the safety of this drug. Include an updated estimate of use for drug marketed in other countries. (8) Provide English translations of current approved foreign labeling not previously submitted. U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov Reference ID: 5810235 NDA 217644 Page 5 ADDITIONAL COMMENTS Product Quality OTHER Within one year after the date of this letter, you are required to resubmit or take other actions available under 21 CFR 314.110. If you do not take one of these actions, we may consider your lack of response a request to withdraw the application under 21 CFR 314.65. You may also request an extension of time in which to resubmit the application. A resubmission must fully address all the deficiencies listed in this letter and should be clearly marked with "RESUBMISSION" in large font, bolded type at the beginning of the cover letter of the submission. The cover letter should clearly state that you consider this resubmission a complete response to the deficiencies outlined in this letter. A partial response to this letter will not be processed as a resubmission and will not start a new review cycle. You may request a meeting or teleconference with us to discuss what steps you need to take before the application may be approved. If you wish to have such a meeting, submit your meeting request as described in the draft guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products. The product may not be legally marketed until you have been notified in writing that this application is approved. U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov Reference ID: 5810235, NDA 217644 Page 6 If you have any questions, contact Sincerely, {See appended electronic signature page} Center for Drug Evaluation and Research U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov Reference ID: 5810235 Signature Page 1 of 1 This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record. (b) (4) 06/04/2026 10:20:25 AM Reference ID: 5810235