UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 6-K
REPORT OF FOREIGN PRIVATE ISSUER
PURSUANT TO SECTION 13a-16 OR 15d-16
UNDER THE SECURITIES EXCHANGE ACT OF 1934
For the month of March, 2022
Commission File Number: 001-36815
Ascendis Pharma A/S
(Exact Name of Registrant as Specified in Its Charter)
Tuborg Boulevard 12
DK-2900 Hellerup
Denmark
(Address of principal executive offices)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.
Form 20-F ☒ Form 40-F ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1): ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ☐
Ascendis Pharma A/S (the “Company”) is hereby furnishing as Exhibit 99.1 the attached presentation relating to the Company’s top-line data from the randomized, double-blind, placebo-controlled portion of its Phase 3 PaTHway Trial of TransCon PTH in adult hypoparathyroidism.
The furnishing of the attached presentation is not an admission as to the materiality of any information therein. The information contained in the presentation is summary information that is intended to be considered in the context of more complete information included in the Company’s filings with the Securities and Exchange Commission (the “SEC”) and other public announcements that the Company has made and may make from time to time. The Company undertakes no duty or obligation to update or revise the information contained in this report, although it may do so from time to time as its management believes is appropriate. Any such updating may be made through the filing or furnishing of other reports or documents with the SEC or through other public disclosures.
Exhibit
| 99.1 | Company Presentation. |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Ascendis Pharma A/S | ||||||
| Date: March 14, 2022 | By: | /s/ Michael Wolff Jensen | ||||
| Michael Wolff Jensen | ||||||
| Senior Vice President, Chief Legal Officer | ||||||
TransCon™ PTH Top-Line Data from Phase 3 PaTHway Trial March 13, 2022 Exhibit 99.1
Cautionary Note on Forward-Looking Statements This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, such as statements regarding our future results of operations and financial position, including our business strategy, prospective products, clinical trial results, product approvals and regulatory pathways, collaborations, licensing or other arrangements, the scope, support progress, results and costs of developing our product candidates or any other future product candidates, the potential market size and size of the potential patient populations for our product candidates, timing and likelihood of success, plans and objectives of management for future operations, the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates, and future results of current and anticipated products, are forward-looking statements. These forward- looking statements are based on our current expectations and beliefs, as well as assumptions concerning future events. These statements involve known and unknown risks, uncertainties and other factors that could cause our actual results to differ materially from the results discussed in the forward-looking statements. These risks, uncertainties and other factors are more fully described in our reports filed with or submitted to the Securities and Exchange Commission, including, without limitation, our preliminary prospectus supplement related to the proposed public offering and our most recent Annual Report on Form 20-F filed with the SEC on March 2, 2022 particularly in the sections titled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations”. In light of the significant uncertainties in our forward-looking statements, you should not place undue reliance on these statements or regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified timeframe, or at all. Any forward-looking statement made by us in this presentation speaks only as of the date of this presentation and represents our estimates and assumptions only as of the date of this presentation. Except as required by law, we assume no obligation to update these statements publicly, whether as a result of new information, future events, changed circumstances or otherwise after the date of this presentation. This presentation concerns product candidates that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration, European Medicines Agency or other foreign regulatory authorities. These product candidates are currently limited by U.S. Federal law to investigational use, and no representations are made as to their safety or effectiveness for the purposes for which they are being investigated. Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo, TransCon, and SKYTROFA are trademarks owned by the Ascendis Pharma group. © March 2022 Ascendis Pharma A/S.
TransCon PTH PaTHway Trial Top-Line Data at Week 26 PaTHway Trial met primary and all key secondary endpoints 78.7% of patients (48 of 61) treated with TransCon PTH achieved the primary endpoint, compared to 4.8% (1 of 21) of patients in the control group (p-value <0.0001) Statistically significant improvements observed on all key prespecified secondary endpoints compared to control: HPES Symptom measures: Physical domain score (p-value = 0.0038) and Cognitive domain score (p-value = 0.0055) HPES Impact measures: Physical Functioning domain score (p-value = 0.0046) and Daily Life domain score (p-value = 0.0061) SF-36v2® - Physical Functioning subscale score (p-value = 0.0347) TransCon PTH was generally well tolerated, with no discontinuations related to study drug 82% of TransCon PTH patients and 100% of patients in control group reported treatment-emergent adverse events (TEAEs), the majority of which were Grade 1, 2 in severity. One serious related TEAE in the TransCon PTH arm was reported due to a dosing error One death in the TransCon PTH arm was assessed as unrelated to study drug TransCon PTH-treated patients showed a mean decrease in 24-hour urine calcium excretion into the normal range, from 390 mg/24 hours down to 220 mg/24 hours HPES, Hypoparathyroidism Patient Experience Scales.
Chronic Hypoparathyroidism: Significant Patient Population Estimated Prevalence: ~200K in these 3 regions ~25k–32k ~25k–32k Japan 2017. Shishiba et. al., Prevalence of postsurgical hypoparathyroidism in Japan: Estimated from the data of multiple institutes 1999. Nakamura et. al., Prevalence of Idiopathic Hypoparathyroidism and Pseudohypoparathyroidism in Japan Ascendis market research ~86k–223k 2013, Underbjerg et. al., Cardiovascular and Renal Complications to Postsurgical Hypoparathyroidism: A Danish Nationwide Controlled Historic Follow-up Study 2015, The Epidemiology of Nonsurgical Hypoparathyroidism in Denmark: A Nationwide Case Finding Study 2016, Astor et. al., Epidemiology and Health-Related Quality of Life in Hypoparathyroidism in Norway Europe ~25k–32k ~70k–112k 2013, Powers et. al., Prevalence and Incidence of Hypoparathyroidism in the United States Using a Large Claims Database, JBMR 2011, Clarke et. al., Co-morbid Medical Conditions Associated with Prevalent Hypoparathyroidism: A Population-Based Study USA
Hypoparathyroidism: Multiple Complications Shobak DM et. al. J Clin Endocrinol Metab. 2016 June 01;101(6):2300-2312. Brain fog Fatigue Pain Numbness & tingling Infections Anxiety & depression Abnormal skeletal dynamics Renal failure Abnormal tissue calcifications Arrhythmias Muscle spasms Heart failure Seizures Laryngospasm & bronchospasm
TransCon PTH PaTHway (Phase 3) Trial 1 No increase in prescribed study drug within 4 weeks prior to Week 26 visit. 2 If needed to meet recommended dietary intake of calcium, it was permitted to take calcium supplements ≤600 mg/day as a nutritional supplement. Double-blind, placebo-controlled trial with an open-label extension period adults with chronic hypoparathyroidism randomized 3:1 (TransCon PTH:placebo) TransCon PTH 18 mcg/day TransCon PTH (titrated according to algorithm) Placebo Placebo TransCon PTH TransCon PTH Open-Label Extension period (156 weeks) Double-Blind Main period (26 weeks) Week 26 Primary Objective Confirm treatment effect of TransCon PTH in adults with hypoparathyroidism Key Eligibility Criteria Adults with chronic hypoparathyroidism (i.e. for at least 26 weeks) Age ≥18 years Reliant on calcitriol ≥0.50 mcg per day or alfacalcidol ≥1.0 mcg per day, and therapeutic elemental calcium ≥800 mg/day for at least 12 weeks prior to screening Serum calcium in normal (or just below normal) range: 7.8–10.6 mg/dL (1.96–2.64 mmol/L) No PTH or PTHrP therapy within 4 weeks prior to Screening Countries Europe (Germany, Denmark, Norway, Italy, Hungary) North America (United States, Canada) Primary Composite Endpoint at Week 261 Proportion of patients with: Serum calcium in the normal range (8.3–10.6 mg/dL) and Independence from active vitamin D and Independence from calcium supplements2 Key Secondary Endpoints at Week 26 HPES Symptom - Physical domain score HPES Symptom - Cognitive domain score HPES Impact – Physical Functioning domain score HPES Impact – Daily Life domain score SF-36 - Physical Functioning subscale score
Data on file, Ascendis Pharma 2022. PaTHway Trial Patient Disposition Intention To Treat (ITT): All randomized patients who received at least 1 dose of randomized treatment Safety Analysis Set (SAS): All randomized patients who received at least 1 dose of randomized treatment Randomized N = 84 TransCon PTH N = 63 TransCon PTH Dosed N = 61 TransCon PTH Completed Week 26 N = 60 Placebo N = 21 Placebo Dosed N = 21 Placebo Completed Week 26 N = 19 TransCon PTH Not Treated N = 2 (1 withdrew consent; 1 recurrence of thyroid cancer) TransCon PTH Discontinued Trial N = 1 (death unrelated to study drug) Placebo Discontinued Trial N = 2 (1 withdrew consent; 1 for adverse event of breast cancer) ITT POPULATION
Patients Who Discontinued Trial during Blinded Treatment Period Randomized Arm Off Study Day Off Study Reason Placebo 30 Withdrew consent Placebo 62 Breast cancer TransCon PTH 111 Cardiac arrest Data on file, Ascendis Pharma 2022. All discontinuations were unrelated to study drug
Patient Demographics
Demographics and Baseline Characteristics Data on file, Ascendis Pharma 2022. Characteristics TransCon PTH (N = 61) Placebo (N = 21) Age (years) (n) 61 21 Mean (SD) 49.0 (13.1) 47.3 (11.4) Age Group (years) – n (%) <50 28 (45.9) 14 (66.7) ≥50 33 (54.1) 7 (33.3) Sex at Birth n (%) Female 46 (75.4) 18 (85.7) Body Mass Index (kg/m2) (n) 61 21 Mean (SD) 27.3 (5.8) 29.5 (5.7) Menopausal Status – n (%) 46 18 Postmenopausal 19 (41.3) 3 (16.7)
Demographics and Baseline Characteristics (continued) Data on file, Ascendis Pharma 2022. Characteristics TransCon PTH (N = 61) Placebo (N = 21) Race – n (%) American Indian or Alaska Native 0 0 Asian 3 (4.9) 2 (9.5) Black or African American 0 0 Native Hawaiian or Other Pacific Islander 0 0 White 57 (93.4) 19 (90.5) Other 1 (1.6) 0 Geographic Region – n (%) North America 39 (63.9) 12 (57.1) Europe 22 (36.1) 9 (42.9)
Hypoparathyroidism Disease Etiology and Medical History Data on file, Ascendis Pharma 2022. Characteristics TransCon PTH (N = 61) Placebo (N = 21) Cause of Hypoparathyroidism (HP) Acquired from neck surgery 52 (85.2) 18 (85.7) Autoimmune disease 1 (1.6) 0 Intrinsic genetic defects of the parathyroid glands 3 (4.9) 0 Idiopathic disease 4 (6.6) 3 (14.3) Other 1 (1.6) 0 Duration of HP (Years) (n) 61 21 Mean 12.0 11.1 Min, Max 1, 56 1, 33 Patient History Renal Insufficiency History 5 (8.2) 1 (4.8) Kidney Stones History 15 (24.6) 4 (19.0) Ectopic Calcifications History 0 0 Vascular Calcifications History 1 (1.6) 0 Brain Calcification History 1 (1.6) 0 Cataract History 3 (4.9) 0 Seizure History 0 1 (4.8)
Baseline Conventional Therapy Conventional Therapy Total Daily Dose (TDD) at Baseline TransCon PTH (N = 61) Placebo (N = 21) Calcium Supplement/TDD (mg) (n) 61 21 Mean 1748 2105 Min, Max 600, 5000 800, 7200 Calcitriol (Active Vitamin D) /TDD (µg) (n) 53 17 Mean 0.76 0.69 Min, Max 0.5, 2.0 0.5, 1.75 Alfacalcidol (Active Vitamin D) /TDD (µg) (n) 8 4 Mean 2.5 2.0 Min, Max 1.0, 4.0 1.5, 2.5 2 patients did not have eDiary information confirmed by prescription information. Data on file, Ascendis Pharma 2022.
Baseline Albumin-Adjusted Serum Calcium & 24-Hour Urine Calcium sCA, serum calcium. Data on file, Ascendis Pharma 2022. Lab Summary at Baseline TransCon PTH (N = 61) Placebo (N = 21) Albumin-Adjusted sCa (mg/dL) (n) 61 21 Mean (SD) 8.8 (0.7) 8.6 (0.6) 24-Hour Urine Calcium (mg/dL) (n) 60 21 Mean (SD) 392 (175) 329 (140)
Trial Results
Primary Composite Endpoint at Week 26 1 CMH test controlling for etiology of hypoparathyroidism (post-surgical vs other). 2 The normal range for albumin-adjusted sCa is 8.3-10.6 mg/dL (2.07-2.64 mmol/L). Patients with missing data on one or more of the criteria are considered as non-responders. Data on file, Ascendis Pharma 2022. TransCon PTH (N = 61) Placebo (N = 21) Number of Patients Meeting The Primary Endpoint Criteria at Week 26 (responders) 48 1 Proportion (95% CI), % 78.7% (66.3%, 88.1%) 4.8% (0.1%, 23.8%) Hypothesis Test: p-value (TransCon PTH vs Placebo) 1 <0.0001 Number of Patients Meeting Each Component, (n): Albumin-adjusted sCa within the normal range 2 49 10 Independence from active vitamin D 60 5 Independence from therapeutic doses of calcium supplements 57 1 No increase in prescribed study drug 57 12 Three patients with missing data for at least one of the components are considered as non-responders. TransCon PTH demonstrated a response rate of 78.7% compared to 4.8% for control (p-value <0.0001)
Active Vitamin D Dose (Mean +/- SE) by Visit Data on file, Ascendis Pharma 2022. TransCon PTH patients discontinued active vitamin D completely within four weeks Active Vitamin D Dose µg/day Mean (± SE) Weeks
Calcium Supplement Dose (Mean +/- SE) by Visit TransCon PTH enabled rapid and sustained calcium supplement reduction Calcium Dose mg/day Mean (± SE) Weeks
Albumin-adjusted Serum Calcium (Mean +/- SE) by Visit TransCon PTH patients maintained mean serum calcium levels in the normal range at all study visits Calcium Corrected for Albumin mg/dL Mean (± SE) Weeks
Key Secondary Endpoints: Patient Reported Symptom & Quality of Life Domains P-values are TransCon PTH vs Control. For HPES, lower scores indicate improvement; for SF-36, higher scores indicate improvement. Data on file, Ascendis Pharma 2022. HPES Symptom Physical domain score All prespecified key secondary endpoints demonstrated statistically significant improvement compared to control HPES Symptom Cognitive domain score HPES Impact Physical Functioning domain score HPES Impact Daily Life domain score SF-36 Physical Functioning subscale score Weeks Weeks Weeks Weeks Weeks p-value = 0.0038 p-value = 0.0347 p-value = 0.0055 p-value = 0.0046 p-value = 0.0061 TransCon PTH Placebo
Bone Turnover Markers: P1NP and CTx (Mean +/- SE) by Visit P1NP, procollagen type 1 N-terminal propeptide CTx, C-terminal telopeptides of type I collagen Data on file, Ascendis Pharma 2022. Procollagen 1N-Terminal Propeptide ng/mL Mean (± SE) Similar pattern exhibited at Week 26 in Phase 2 PaTH Forward Trial Mean P1NP Type I Collagen C-Telopeptides ng/L Mean (± SE) Mean CTx Weeks Weeks
Safety Results
Overall TEAE Summary *In the severity categories, patients are displayed for the highest severity category only. **Death due to cardiac arrest Data on file, Ascendis Pharma 2022. TEAE Summary TransCon PTH (N = 61); n (%) Placebo (N = 21); n (%) Treatment-Emergent Adverse Events (TEAE) 50 (82.0) 21 (100.0) Serious TEAE 5 (8.2) 3 (14.3) Severity* Grade ≥3 2 (3.3) 1 (4.8) Grade 2 21 (34.4) 9 (42.9) Grade 1 27 (44.3) 11 (52.4) Related TEAE 30 (49.2) 8 (38.1) Serious Related TEAE 1 (1.6) 0 TEAE Related to Hyper- or Hypocalcaemia Leading to ER/Urgent Care Visit and/or Hospitalization 4 (6.6) 2 (9.5) TEAE Leading to Discontinuation of Study Drug 1 (1.6)** 2 (9.5)
Treatment-Emergent Adverse Events (≥5 patients in total) Data on file, Ascendis Pharma 2022. Preferred Term TransCon PTH (N = 61) Placebo (N = 21) Patients with at least one TEAE, n (%) 50 (82.0) 21 (100.0) TEAEs Injection site reaction 19 (31.1) 0 Headache 13 (21.3) 2 (9.5) Hypocalcaemia 6 (9.8) 9 (42.9) Fatigue 9 (14.8) 5 (23.8) Paraesthesia 11 (18.0) 3 (14.3) Muscle spasms 7 (11.5) 3 (14.3) Nausea 7 (11.5) 2 (9.5) Arthralgia 6 (9.8) 2 (9.5) Diarrhoea 6 (9.8) 1 (4.8) Hypercalcaemia 6 (9.8) 0 Constipation 4 (6.6) 1 (4.8) Insomnia 4 (6.6) 1 (4.8)
24-Hour Urine Calcium (mg/d) by Visit 1 The ANCOVA model with unequal variance includes the change from baseline as the response variable, treatment and etiology of HP as fixed effects and baseline value of the parameter as a covariate. 2 p-values from t-test. Data on file, Ascendis Pharma 2022. 24-Hour Urine Calcium (mg/d) Mean (± SE) Baseline (Week 0) Visit 7 (Week 12) Visit 10 (Week 26) p-value2 <0.0001 p-value2 =0.24 24-Hour Urine Calcium (mg/d), Change from baseline at Week 26 TransCon PTH (N = 61) Placebo (N = 21) ANCOVA Model (n) 1 LS Mean (SE), mg/d -154 (21) -64 (32) 95% CI for LS Mean (-197, -112) (-131, 2) Difference in LS Means (SE) -90 (32) 95% CI for Difference in LS Means (-155, -25) p-value (TransCon PTH vs Placebo) 0.0085 TransCon PTH Placebo
TransCon PTH PaTHway Trial Top-line Data at Week 26 PaTHway Trial met primary and all key secondary endpoints 78.7% of patients (48 of 61) treated with TransCon PTH achieved the primary endpoint, compared to 4.8% (1 of 21) of patients in the control group (p-value <0.0001) Statistically significant improvements observed on all key prespecified secondary endpoints compared to control: HPES Symptom measures: Physical domain score (p-value = 0.0038) and Cognitive domain score (p-value = 0.0055) HPES Impact measures: Physical Functioning domain score (p-value = 0.0046) and Daily Life domain score (p-value = 0.0061) SF-36v2 - Physical Functioning subscale score (p-value = 0.0347) TransCon PTH was generally well tolerated, with no discontinuations related to study drug 82% of TransCon PTH patients and 100% of patients in control group reported treatment-emergent adverse events (TEAEs), the majority of which were Grade 1, 2 in severity. One serious related TEAE in the TransCon PTH arm was reported due to a dosing error One death in the TransCon PTH arm was assessed as unrelated to study drug TransCon PTH-treated patients showed a mean decrease in 24-hour urine calcium excretion into the normal range, from 390 mg/24 hours down to 220 mg/24 hours
Program Status and Next Steps Two Open-Label Extension trials continuing 57 of 59 patients remain in PaTH Forward Trial after two years All 79 patients who completed the blinded period continue in the PaTHway Trial Engage with regulatory authorities regarding registration plans for US and EU Anticipated NDA submission to FDA during Q3, 2022 Anticipated MAA submission to EMA during Q4, 2022 Continue adult TransCon PTH trial in China* Japan Phase 3 top-line data expected in Q3, 2022 Plan to initiate pediatric TransCon PTH trial in Q4, 2022 *In development in Greater China through strategic investment in VISEN Pharmaceuticals.
Thank you Contact Tim Lee ir@ascendispharma.com