A Phase 3, Multicenter, Single Arm, Open-Label Trial, Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Subcutaneously Daily in Japanese Adult Subjects with Hypoparathyroidism - PaTHway Japan Trial

开始日期2021-11-02

申办/合作机构-

NCT04701203 / Active, not recruiting临床3期

PaTHway TRIAL: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial, With an Open-Label Extension, Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Subcutaneously Daily in Adults With Hypoparathyroidism

During the first 26 weeks of the trial, participants will be randomly assigned to one of two groups: one group will receive TransCon PTH and one group will receive placebo. All subjects will start with a fixed dose of study drug and will be individually and progressively titrated to an optimal dose over a 10 week period, followed by an individualized dosing period up to 16 weeks. TransCon PTH or placebo will be administered as a subcutaneous injection using a pre-filled injection pen. Neither trial participants nor their doctors will know who has been assigned to each group. After the 26 weeks, participants will continue in the trial as part of a long-term extension study. During the extension, all participants will receive TransCon PTH, with the dose adjusted to their individual needs. This is a global trial that will be conducted in, but not limited to, the United States, Canada, Germany, and Denmark.

开始日期2021-02-16

申办/合作机构

Ascendis Pharma Bone Diseases A/S

NCT04009291 / Active, not recruiting临床2期

PaTH Forward: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial With an Open-Label Extension, Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Subcutaneously Daily in Adults With Hypoparathyroidism

During the first four weeks of the trial, participants will be randomly assigned to one of four groups: three groups will receive fixed doses of TransCon PTH and one group will receive placebo. TransCon PTH or placebo will be administered as a subcutaneous injection using a pre-filled injection pen. Neither trial participants nor their doctors will know who has been assigned to each group. After the four weeks, participants will continue in the trial as part of a long-term extension study. During the extension, all participants will receive TransCon PTH, with the dose adjusted to their individual needs. This is a global trial that will be conducted in, but not limited to, the United States, Canada, Germany, Denmark, and Norway.

开始日期2019-08-27

申办/合作机构

Ascendis Pharma A/S

100 项与帕罗培特立帕肽相关的临床结果

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100 项与帕罗培特立帕肽相关的转化医学

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100 项与帕罗培特立帕肽相关的专利（医药）

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项与帕罗培特立帕肽相关的文献（医药）

2022-01-01·The Journal of clinical endocrinology and metabolism2区 · 医学

PaTH Forward: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of TransCon PTH in Adult Hypoparathyroidism

2区 · 医学

Article

作者: Pagotto, Uberto ; Karpf, David B ; Rubin, Mishaela ; Vokes, Tamara ; Eriksen, Erik ; Palermo, Andrea ; Brod, Meryl ; Clarke, Bart ; Mourya, Sanchita ; Khan, Aliya A ; Smith, Alden ; Schwarz, Peter ; Pihl, Susanne ; Shu, Aimee D ; Rejnmark, Lars ; Marcocci, Claudio ; Markova, Denka ; Ahmed, Intekhab ; Hofbauer, Lorenz

Abstract:

Context:

Hypoparathyroidism is characterized by insufficient levels of parathyroid hormone (PTH). TransCon PTH is an investigational long-acting prodrug of PTH(1-34) for the treatment of hypoparathyroidism.

Objective:

This work aimed to investigate the safety, tolerability, and efficacy of daily TransCon PTH in adults with hypoparathyroidism.

Methods:

This phase 2, randomized, double-blind, placebo-controlled 4-week trial with open-label extension enrolled 59 individuals with hypoparathyroidism. Interventions included TransCon PTH 15, 18, or 21 µg PTH(1-34)/day or placebo for 4 weeks, followed by a 22-week extension during which TransCon PTH dose was titrated (6-60 µg PTH[1-34]/day).

Results:

By Week 26, 91% of participants treated with TransCon PTH achieved independence from standard of care (SoC, defined as active vitamin D = 0 μg/day and calcium [Ca] ≤ 500 mg/day). Mean 24-hour urine Ca (uCa) decreased from a baseline mean of 415 mg/24h to 178 mg/24h by Week 26 (n = 44) while normal serum Ca (sCa) was maintained and serum phosphate and serum calcium-phosphate product fell within the normal range. By Week 26, mean scores on the generic 36-Item Short Form Health Survey domains increased from below normal at baseline to within the normal range. The Hypoparathyroidism Patient Experience Scale symptom and impact scores improved through 26 weeks. TransCon PTH was well tolerated with no treatment-related serious or severe adverse events.

Conclusion:

TransCon PTH enabled independence from oral active vitamin D and reduced Ca supplements (≤ 500 mg/day) for most participants, achieving normal sCa, serum phosphate, uCa, serum calcium-phosphate product, and demonstrating improved health-related quality of life. These results support TransCon PTH as a potential hormone replacement therapy for adults with hypoparathyroidism.

2021-12-01·Journal of patient-reported outcomes

Psychometric validation of the Hypoparathyroidism Patient Experience Scales (HPES)

Article

作者: Brod, Meryl ; Gianettoni, Jill ; Shu, Aimee ; Smith, Alden ; Markova, Denka ; Lin, Zhengning ; McLeod, Lori ; Mourya, Sanchita

Abstract:

Background:

Hypoparathyroidism (HP) is a rare endocrine disorder characterized by absent or inappropriately low levels of circulating parathyroid hormone with associated significant physical and cognitive symptoms. This study evaluated the psychometric properties of the Hypoparathyroidism Patient Experience Scales (HPES), which were developed as disease-specific, patient-reported outcome (PRO) measures to assess the symptoms and impacts associated with HP in adults.

Methods:

Data from a non-interventional, observational study (N = 300) and a Phase 2 clinical trial (N = 59) were used in the psychometric evaluation. Observational and trial assessments included: an online validation battery (baseline or screening) and retest (approximately 2 weeks after baseline or screening). In the trial, the primary efficacy endpoint was assessed at week 4 through re-administration of the HPES and validation battery subset. The observational study’s larger sample size allowed for evaluation of the HPES descriptive properties, scoring algorithm, test-retest reliability, and construct validity. The trial data examined responsiveness, meaningful within-patient change estimates, and treatment impact on HPES scores.

Results:

Demographic and self-reported medical characteristics results were similar across the 2 studies. Factor analysis confirmed domains in the HPES-Symptom (n = 2) and HPES-Impact (n = 4). For both measures, total and domain scores demonstrated acceptable reliability and validity for both the observational and trial samples. Internal consistency evidence was strong. Test-retest reliability estimates generally approached the recommended 0.70 threshold. The construct validity correlations with other PRO measures were mainly as hypothesized, thus supporting the HPES scores and constructs. Mean scores for both measures also differed as anticipated and significantly across known-groups, thus providing evidence for the scores discriminating between meaningful groups. Trial results supported both HPES total and domain scores’ ability to detect change. The difference in mean total and domain scores for both measures demonstrated statistically significant improvements for TransCon PTH compared to placebo treated subjects despite the small sample and a short 4-week duration on fixed, non-optimized doses.

Conclusions:

The HPES were found to be conceptually sound with adequate evidence supporting their reliability and validity. Incorporation of the HPES into clinical and research settings will help to further elucidate and assess the patient experience of living with HP and identify treatment differences.

2020-12-01·Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial

Article

作者: Vokes, Tamara ; Abbott, Lisa G ; Gagnon, Claudia ; Ukena, Jenny ; Eng, Walter Frank ; Khan, Aliya A ; Sibley, Christopher T ; Rubin, Mishaela R ; Schwarz, Peter ; Clarke, Bart L ; Rejnmark, Lars ; Shu, Aimee D ; Marcocci, Claudio ; Kohlmeier, Lynn ; Pihl, Susanne ; An, Xuebei ; Smith, Alden R ; Palermo, Andrea ; Hofbauer, Lorenz C ; Shoback, Dolores M

ABSTRACT:

Conventional therapy for hypoparathyroidism consisting of active vitamin D and calcium aims to alleviate hypocalcemia but fails to restore normal parathyroid hormone (PTH) physiology. PTH replacement therapy is the ideal physiologic treatment for hypoparathyroidism. The double-blind, placebo-controlled, 26-week, phase 3 PaTHway trial assessed the efficacy and safety of PTH replacement therapy for hypoparathyroidism individuals with the investigational drug TransCon PTH (palopegteriparatide). Participants (n = 84) were randomized 3:1 to once-daily TransCon PTH (initially 18 μg/d) or placebo, both co-administered with conventional therapy. The study drug and conventional therapy were titrated according to a dosing algorithm guided by serum calcium. The composite primary efficacy endpoint was the proportion of participants at week 26 who achieved normal albumin-adjusted serum calcium levels (8.3–10.6 mg/dL), independence from conventional therapy (requiring no active vitamin D and ≤600 mg/d of calcium), and no increase in study drug over 4 weeks before week 26. Other outcomes of interest included health-related quality of life measured by the 36-Item Short Form Survey (SF-36), hypoparathyroidism-related symptoms, functioning, and well-being measured by the Hypoparathyroidism Patient Experience Scale (HPES), and urinary calcium excretion. At week 26, 79% (48/61) of participants treated with TransCon PTH versus 5% (1/21) wiplacebo met the composite primary efficacy endpoint (p < 0.0001). TransCon PTH treatment demonstrated a significant improvement in all key secondary endpoint HPES domain scores (all p < 0.01) and the SF-36 Physical Functioning subscale score (p = 0.0347) compared with placebo. Additionally, 93% (57/61) of participants treated with TransCon PTH achieved independence from conventional therapy. TransCon PTH treatment normalized mean 24-hour urine calcium. Overall, 82% (50/61) treated with TransCon PTH and 100% (21/21) wiplacebo experienced adverse events; most were mild (46%) or moderate (46%). No study drug-related withdrawals occurred. In conclusion, TransCon PTH maintained normocalcemia while permitting independence from conventional therapy and was well-tolerated in individuals with hypoparathyroidism. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).AbstractTransCon PTH is an investigational once-daily prodrug providing sustained release of active PTH designed to maintain stable PTH levels in the physiological range for 24 hours/day. The PaTHway trial met all primary and key secondary endpoints with statistically significant differences from placebo. Most adverse events (AEs) were mild/moderate. Injection-site reactions and headaches were the most common treatment-related AEs.

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项与帕罗培特立帕肽相关的新闻（医药）

2024-09-04

·Endpoints

Vaxcyte aims to raise $1B after sharing pneumococcal vaccine data; More layoffs at Genentech

Plus, news about Anthos, Ascendis, Royalty Pharma, Semnur, Sonoma, Atara, Feldan, Indivior, Aelis Farma and Acepodia: Vaxcyte launches $1B offering: The raise comes fresh off the company’s pneumococcal vaccine data that sent its stock $PCVX soaring on Tuesday. Vaxcyte selected VAX-31 to advance to a Phase 3 trial in mid-2025 over another vaccine, VAX-24. It can tack on an additional $150 million if all the options are exercised. — Max Gelman Genentech to lay off 93 staffers: In another round of layoffs, Roche’s Genentech is cutting 93 roles at its South San Francisco site starting in October, according to a Californian WARN notice. The site houses over 40 buildings and includes scientific research, manufacturing and other business functions. Genentech said earlier this year that it has plans to cut around 400 workers and restructure its portfolio . — Anna Brown Anthos Therapeutics suggests patients can stay on experimental anticoagulant before surgery: The company on Tuesday shared additional data from a clinical study of its once-monthly factor XI antibody treatment in people with atrial fibrillation, suggesting they do not need to interrupt treatment with abelacimab before elective procedures. In the study, people on the control arm received Xarelto and were allowed to stop taking it 24 to 48 hours prior to their procedure. Seven of 852 patients (0.8%) in the abelacimab arm had major procedure-related bleeds, compared to 6 of 428 (1.4%) in the Xarelto arm. — Lei Lei Wu Ascendis snags $150M in new Royalty Pharma deal: Less than a month after snagging FDA approval for Yorvipath, Ascendis is selling off US royalties of the hypoparathyroidism drug. In exchange for paying $150 million upfront, Royalty Pharma gets 3% royalties on new US sales. The length of the payments is contingent on how quickly Royalty earns back its investment. — Max Bayer Semnur hits Wall Street via SPAC: The company is merging with special-acquisition company Denali Capital Acquisition Corp. in a $2.5 billion deal. Semnur is owned by Scilex Holding Company, which itself took the SPAC route to go public in 2022. — Max Bayer Sonoma Biotherapeutics records $45M milestone: The payment from Regeneron Pharmaceuticals stems from a deal inked in 2023 to develop and commercialize T cell therapies for inflammatory bowel disease and two other undisclosed indications. — Jaimy Lee Atara Biotherapeutics seeks $36M: The company raised the money in a registered direct offering, getting funding from Redmile Group, EcoR1 Capital and Adiumentum Capital Management. An unnamed “large public biotechnology company” also participated in the offering. — Max Gelman Feldan Therapeutics closes $21M Series B: The money will go toward completing a Phase 1/2a trial for the company’s non-invasive intralesional treatment for basal cell carcinoma, which is meant to be an alternative to surgery. Genesys Capital and Fonds de solidarité FTQ co-led the round . — Katherine Lewin Indivior, Aelis Farma drug fails Phase 2b trial: A study investigating a treatment for patients with moderate-to-severe cannabis use disorder didn’t hit the primary or secondary endpoints. The primary endpoint was the proportion of participants who reduced their cannabis use to one day or less per week. Indivior said it will not exercise an exclusive option to license the global rights to the treatment. — Katherine Lewin Acepodia inks Pfizer Ignite collab: The company is collaborating with Pfizer Ignite to advance its off-the-shelf cell therapies to treat autoimmune diseases. Financial terms weren’t disclosed. Acepodia said it retained all rights to its lead program, ACE1831, and Pfizer Ignite “will provide strategic guidance and resources.” — Max Bayer

疫苗临床2期细胞疗法临床结果并购

2024-09-03

·BioSpace

Ascendis Pharma Reports Second Quarter 2024 Financial Results

YORVIPATH approved by U.S. Food & Drug Administration (FDA) as the first and only treatment of hypoparathyroidism in adults TransCon CNP (navepegritide) pivotal ApproaCH Trial topline results expected in the coming weeks SKYTROFA Q2 revenue of €26 million – 134% year-over-year volume growth offset by negative adjustment of €27 million, resetting market access for continued growth Revising full year 2024 SKYTROFA revenue outlook to €220 - €240 million Conference call today at 4:30 pm ET COPENHAGEN, Denmark, Sept. 03, 2024 (GLOBE NEWSWIRE) -- Ascendis Pharma A/S (Nasdaq: ASND) today announced financial results for the second quarter ended June 30, 2024, and provided a business update. “The recent FDA approval of YORVIPATH demonstrates why our unrelenting focus on helping patients suffering from hypoparathyroidism and other serious diseases with considerable unmet need is so important for Ascendis,” said Jan Mikkelsen, Ascendis Pharma’s President and Chief Executive Officer. “Already, two out of our three Endocrine Rare Disease TransCon product candidates have been approved by the FDA and European Commission. Our first, SKYTROFA, has achieved U.S. market value leadership, and, we believe, now with broader market access, remains well positioned to reach blockbuster status in the U.S. alone. Looking forward, we are preparing for our second U.S. launch with YORVIPATH and are on track to report pivotal data in the coming weeks for our third TransCon product candidate, TransCon CNP.” Select Highlights & Anticipated 2024 Milestones TransCon hGH: (lonapegsomatropin, marketed as SKYTROFA) SKYTROFA revenue for the second quarter of 2024 totaled €26.2 million, a 27% year-over-year decrease compared to €35.9 million during the same period in 2023. 134% year-over-year volume growth was offset by the cost associated with broader market access for SKYTROFA which also resulted in a negative adjustment to prior period sales deductions of €27.1 million, where €19.5 million and €7.6 million were attributable to the three months ended March 31, 2024, and periods prior to January 1, 2024, respectively. SKYTROFA revenue for the first half of 2024 totaled €91.2 million, a 35% year-over-year increase compared to €67.4 million during the same period of 2023. 159% year-over-year volume growth was offset by the cost associated with broader market access for SKYTROFA which also resulted in a negative adjustment to prior period sales deductions of €7.6 million, which were attributable to periods prior to January 1, 2024. On track to submit a supplemental Biologics License Application to the FDA for adult growth hormone deficiency in the third quarter of 2024. Topline results from Phase 2 New InsiGHTS Trial in Turner syndrome expected in the fourth quarter of 2024. TransCon PTH: (palopegteriparatide, marketed as YORVIPATH) Received U.S. FDA approval for TransCon PTH, under the brand name YORVIPATH, for the treatment of hypoparathyroidism in adults. Completing manufacturing of commercial product for the U.S. market and anticipate initial supply will be available in the first quarter of 2025. The Company is in dialogue with the FDA about commercialization of existing manufactured product, which if agreed, could be introduced in the U.S. in the fourth quarter of 2024. Second quarter YORVIPATH revenue totaled €5.2 million, reflecting the first full quarter of commercial launch in Germany and Austria as well initial revenue in International Markets. Initial revenue in France expected starting in the fourth quarter of 2024. TransCon CNP (navepegritide) Topline data from pivotal ApproaCH Trial expected in the coming weeks, and, if successful, plan to submit a New Drug Application to FDA for children with achondroplasia (age 2-11 years) in the first quarter of 2025. Plan to complete enrollment in the combination TransCon hGH and TransCon CNP COACH trial of children with achondroplasia (ages 2-11 years) during the third quarter of 2024; topline Week 26 data expected in the second quarter of 2025. Expect to initiate teACH, a Phase 2 trial in adolescents with achondroplasia, in the fourth quarter of 2024. Oncology Programs Presented new and updated results from the ongoing Phase 1/2 IL-Believe Trial of TransCon IL-2 β⁄γ in a poster presentation at ASCO 2024. As of the April 16, 2024, data cutoff, 40% of efficacy-evaluable patients (2 out of 5) in the initial cohort of patients with anti-PD-1 refractory melanoma treated with TransCon IL-2 β⁄γ in combination with TransCon TLR7/8 Agonist exhibited confirmed clinical responses with no new safety signals. Initial results from the Phase 2 dose expansion cohort of the IL-Believe Trial of TransCon IL-2 β⁄γ in combination with chemotherapy in platinum-resistant ovarian cancer (PROC) will be presented later this month at the European Society for Medical Oncology (ESMO) 2024 Congress in Barcelona, Spain. Financial Update and Outlook Based on Current Plans As of June 30, 2024, Ascendis Pharma had cash, cash equivalents, and marketable securities totaling €259 million, compared to €399 million as of December 31, 2023. Full year 2024 SKYTROFA revenue expected to be €220 million to €240 million. Expect total operating expenses (SG&A and R&D) to be approximately €600 million for 2024. Pending launch timing of YORVIPATH in the U.S., expect to be operating cash flow breakeven on a quarterly basis in 2024 or 2025 Subsequent to the quarter end, entered into a $150 million capped synthetic royalty funding agreement with Royalty Pharma relating to net sales of YORVIPATH in the United States. More information on this funding can be found in a separate press release issued today and available here on the Investors & News section of the Ascendis Pharma website. Second Quarter 2024 Financial Results Total revenue for the second quarter of 2024 was €36.0 million, compared to €47.4 million during the same period for 2023. Results in the quarter were primarily impacted by a negative adjustment to prior periods’ estimates and assumptions for sales deductions of €27.1 million, where €19.5 million and €7.6 million were attributable to the three months ended March 31, 2024, and periods prior to January 1, 2024, respectively. This was partially offset by increased demand for SKYTROFA in the U.S. and revenue contribution from YORVIPATH. In addition, non-product revenue was €4.6 million in the second quarter of 2024, compared to €11.5 million during the same period for 2023. Total Revenue (In EUR'000s) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Revenue from external customers Commercial sale of products 31,389 35,895 97,888 67,446 Licenses 869 589 25,639 1,203 Other 3,740 10,909 8,365 12,333 Total revenue from external customers 35,998 47,393 131,892 80,982 Research and development (R&D) costs for the second quarter of 2024 were €83.5 million, compared to €105.0 million during the same period in 2023. The decline was largely tied to lower external development costs for TransCon TLR 7/8 Agonist and lower costs for TransCon PTH, as well as lower employee costs as a result of the Eyconis spin-off. Selling, general, and administrative (SG&A) expenses for the second quarter of 2024 were €74.3 million, compared to €70.3 million during the same period in 2023. The increase was primarily due to higher employee costs, including the impact from commercial expansion. Total operating expenses for the second quarter of 2024 were €157.8 million compared to €175.3 million during the same period in 2023. Net finance income for the second quarter of 2024 was €29.4 million compared to a net finance income of €26.4 million during the same period in 2023. For the second quarter of 2024, Ascendis Pharma reported a net loss of €109.4 million, or €1.91 per share (basic and diluted) compared to a net loss of €121.4 million, or €2.16 per share (basic and diluted) for the same period in 2023. As of June 30, 2024, Ascendis Pharma had cash, cash equivalents, and marketable securities totaling €258.7 million compared to €399.4 million as of December 31, 2023. As of June 30, 2024, Ascendis Pharma had 58,231,484 ordinary shares outstanding, including 881,730 ordinary shares represented by ADSs held by the company. Conference Call and Webcast Information Ascendis Pharma will host a conference call and webcast today at 4:30 pm Eastern Time (ET) to discuss its second quarter 2024 financial results. Those who would like to participate may access the live webcast here , or register in advance for the teleconference here . The link to the live webcast will also be available on the Investors & News section of the Ascendis Pharma website at A replay of the webcast will be available on this section of the Ascendis Pharma website shortly after conclusion of the event for 30 days. About Ascendis Pharma A/S Ascendis Pharma is applying its innovative TransCon technology platform to build a leading, fully integrated biopharma company focused on making a meaningful difference in patients’ lives. Guided by its core values of Patients, Science, and Passion, Ascendis uses its TransCon technologies to create new and potentially best-in-class therapies. Ascendis is headquartered in Copenhagen, Denmark and has additional facilities in Europe and the United States. Please visit ascendispharma.com to learn more. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, included in this press release regarding Ascendis’ future operations, plans and objectives of management are forward-looking statements. Examples of such statements include, but are not limited to, statements relating to (i) the timing of topline results from the ApproaCH Trial, (ii) Ascendis’ expectations regarding full year 2024 SKYTROFA revenue, (iii) Ascendis’ expectations regarding SKYTROFA’s potential to reach blockbuster status, (iv) Ascendis’ plan to submit a supplemental Biologics License Application for SKYTROFA for adult growth hormone deficiency in the third quarter of 2024, (v) the timing of topline results from the Phase 2 trial of TransCon hGH in Turner syndrome, (vi) Ascendis’ plan to submit a New Drug Application for TransCon CNP for children with achondroplasia, (vii) Ascendis’ expectations regarding completing manufacturing of YORVIPATH commercial product for the U.S. market and the timing of initial supply, (viii) dialogue with FDA regarding commercialization of existing YORVIPATH manufactured product and, if agreed, the potential timing of introduction, (ix) Ascendis’ expectations regarding initial revenue in France from YORVIPATH, (x) Ascendis’ plan to complete enrollment in the COACH Trial, (xi) the timing of topline Week 26 data from the COACH Trial, (xii) the timing of initiating the teACH Phase 2 trial in adolescents, (xiii) Ascendis’ plan to present initial results from the Phase 2 dose expansion cohort of the IL-Believe Trial, (xiv) Ascendis’ expectations regarding its total operating expenses for 2024, (xv) Ascendis’ expectation to be operating cash flow breakeven on a quarterly basis in 2024 or 2025, (xvi) Ascendis’ ability to apply its TransCon technology platform to build a leading, fully integrated biopharma company, and (xvii) Ascendis’ use of its TransCon technologies to create new and potentially best-in-class therapies. Ascendis may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions, expectations and projections disclosed in the forward-looking statements. Various important factors could cause actual results or events to differ materially from the forward-looking statements that Ascendis makes, including the following: dependence on third party manufacturers, distributors and service providers for Ascendis’ products and product candidates; unforeseen safety or efficacy results in Ascendis’ development programs or on-market products; unforeseen expenses related to commercialization of any approved Ascendis products; unforeseen expenses related to Ascendis’ development programs; unforeseen selling, general and administrative expenses, other research and development expenses and Ascendis’ business generally; delays in the development of its programs related to manufacturing, regulatory requirements, speed of patient recruitment or other unforeseen delays; Ascendis’ ability to obtain additional funding, if needed, to support its business activities; the impact of international economic, political, legal, compliance, social and business factors. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Ascendis’ business in general, see Ascendis’ Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission (SEC) on February 7, 2024 and Ascendis’ other future reports filed with, or submitted to, the SEC. Forward-looking statements do not reflect the potential impact of any future licensing, collaborations, acquisitions, mergers, dispositions, joint ventures, or investments that Ascendis may enter into or make. Ascendis does not assume any obligation to update any forward-looking statements, except as required by law. Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo, TransCon, SKYTROFA ® , and YORVIPATH ® are trademarks owned by the Ascendis Pharma group. © September 2024 Ascendis Pharma A/S. Investor Contacts: Media Contact: Tim Lee Melinda Baker Ascendis Pharma Ascendis Pharma +1 (650) 374-6343 +1 (650) 709-8875 tle@ascendispharma.com media@ascendispharma.com ir@ascendispharma.com Patti Bank ICR Westwicke +1 (415) 513-1284 patti.bank@westwicke.com FINANCIAL TABLES FOLLOW Ascendis Pharma A/S Consolidated Statements of Profit or Loss and Comprehensive Income / (Loss) (In EUR'000s, except share and per share data) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Consolidated Statement of Profit or Loss Revenue 35,998 47,393 131,892 80,982 Cost of sales 11,465 12,929 19,034 17,551 Gross profit 24,533 34,464 112,858 63,431 Research and development costs 83,478 105,021 154,165 211,134 Selling, general and administrative expenses 74,312 70,281 141,095 136,820 Operating profit/(loss) (133,257 ) (140,838 ) (182,402 ) (284,523 ) Share of profit/(loss) of associate (5,322 ) (7,451 ) (11,118 ) (8,677 ) Finance income 49,052 35,761 14,395 80,374 Finance expenses 19,624 9,334 58,553 18,652 Profit/(loss) before tax (109,151 ) (121,862 ) (237,678 ) (231,478 ) Income taxes/(expenses) (229 ) 429 (2,737 ) (868 ) Net profit/(loss) for the period (109,380 ) (121,433 ) (240,415 ) (232,346 ) Attributable to owners of the Company (109,380 ) (121,433 ) (240,415 ) (232,346 ) Basic and diluted earnings/(loss) per share € (1.91 ) € (2.16 ) € (4.21 ) € (4.14 ) Number of shares used for calculation (basic and diluted) 57,345,613 56,218,257 57,114,435 56,155,441 (EUR’000) Consolidated Statement of Comprehensive Income or (Loss) Net profit/(loss) for the period (109,380 ) (121,433 ) (240,415 ) (232,346 ) Items that may be reclassified subsequently to profit or loss: Exchange differences on translating foreign operations 15 (1,016 ) 78 (1,803 ) Other comprehensive income/(loss) for the period, net of tax 15 (1,016 ) 78 (1,803 ) Total comprehensive income/(loss) for the period, net of tax (109,365 ) (122,449 ) (240,337 ) (234,149 ) Attributable to owners of the Company (109,365 ) (122,449 ) (240,337 ) (234,149 ) Ascendis Pharma A/S Consolidated Statements of Financial Position (In EUR'000s) June 30, 2024 December 31, 2023 Assets Non-current assets Intangible assets 4,186 4,419 Property, plant and equipment 104,041 110,634 Investment in associates 20,564 5,686 Other receivables 2,186 2,127 130,977 122,866 Current assets Inventories 251,199 208,931 Trade receivables 49,163 35,874 Income tax receivables 1,841 802 Other receivables 29,679 19,097 Prepayments 36,743 38,578 Marketable securities — 7,275 Cash and cash equivalents 258,696 392,164 627,321 702,721 Total assets 758,298 825,587 Equity and liabilities Equity Share capital 7,819 7,749 Distributable equity (328,952 ) (153,446 ) Total equity (321,133 ) (145,697 ) Non-current liabilities Borrowings 219,052 222,996 Contract liabilities 5,000 5,949 Deferred tax liabilities 7,644 5,830 231,696 234,775 Current liabilities Convertible notes, matures in April 2028 Borrowings 432,190 407,095 Derivative liabilities 159,059 143,296 591,249 550,391 Other current liabilities Borrowings 21,397 14,174 Contract liabilities 1,293 1,184 Trade payables and accrued expenses 99,527 94,566 Other liabilities 26,411 41,176 Income tax payables 1,090 2,299 Provisions 106,768 32,719 256,486 186,118 847,735 736,509 Total liabilities 1,079,431 971,284 Total equity and liabilities 758,298 825,587

临床2期上市批准临床结果财报

2024-09-02

·生物制品圈

2023年全球获批上市的原创新药: 回顾与展望

摘要 2023年对于生物医药行业而言是具有里程碑意义的一年，在这一年中美国、欧洲、日本与中国均积极推动新药创制和新兴技术发展，在针对新型疾病的治疗方案、基因编辑技术等领域获得重大突破，利用人工智能/大数据等先进技术提升了研发效率和质量，全球生物医药行业在创新、市场需求、产业链整合和国际化等方面呈现出积极的发展趋势。本文梳理与总结2023年美国、欧洲、日本和中国获批上市的新药，并对2024年新药研发和生物医药发展态势进行展望，以期为新药研发相关研究提供参考。 _ 正文 _ 随着医药科技的飞速进步和临床需求的日益增长，创新药研发已成为引领全球医疗健康领域前行的核心动力。2023年全球新型冠状病毒感染逐渐受控，经济复苏为创新药研发提供了更多资金与市场机遇，全球生物医药市场规模持续扩大，创新药研发的投入和产出均实现了显著增长，然而地缘政治紧张等因素为全球创新药研发带来了一定的挑战与不确定性。美国在创新药研发的全球竞技场中仍占据主力，欧洲与日本也保持强劲竞争力，中国、印度等新兴市场国家基于庞大的患者群体、独特的疾病谱、不断优化的政策环境和日益增强的研发实力，逐渐成为全球新药研发的重要力量。本文对2023年美国、欧洲、日本和中国获批上市的新药进行梳理和重点介绍，并对2024年新药研发和生物医药发展态势进行展望，旨在为新药研发相关研究提供参考。2023年之前已获批上市药物的相关仿制药、新剂型、新适应证以及血液制品等不列入本文讨论范围内。 1 2023年美国FDA批准的全新药物 2023年美国FDA药品评估和研究中心(Center of Drug Evaluation and Research，CDER)共批准了55款新药(见表1)，其在药物设计、作用机制和治疗效果方面展现出高度创新性。20款(36%)为首创类药物(first-in-class)，其适应证范围广泛，涵盖肿瘤、感染、神经系统疾病、罕见病等多个领域，其中，罕见病领域的成绩尤为突出，有28款药物(51%)以孤儿药资格获批。按治疗领域划分，肿瘤学领域获批药物最多，CDER在2023年批准了13款抗肿瘤药物(24%); 神经学领域排名第2，9款药物(16%)获批; 传染病学和血液学领域并列第3，各有5款药物(9%)获批[1]。CDER通过综合应用各种加速开发与审评审批的方法，使得具有显著疗效或针对严重未被满足临床需求的药物更早惠及患者。55款获批新药中，25款(45%)被授予快速通道(fast track)资格，9款(16%)获突破性疗法(breakthrough therapy)认定，31款(56%)获优先审评(priority review)资格，9款(16%)获加速审批(accelerated approval); 共有36款(65%)使用了快速通道、突破性疗法、优先审评和加速审批中的至少1种加速程序[2]。 2023年美国FDA生物制品评价与研究中心(Center for Biologics Evaluation and Research，CBER)批准了25款产品，涉及细胞和基因疗法、疫苗和血液制品[3]。值得一提的是由Vertex公司与CRISPR公司合作开发的exagamglogene autotemcel(商品名: Casgevy)于2023年12月8日获批上市，该产品是一种基于CRISPR/Cas9基因编辑技术的疗法，用于治疗12岁及以上反复出现血管阻塞性危机(vaso-occlusive crisis，VOC)的镰状细胞病(sickle cell disease，SCD)患者，其作为全球首个获批的CRISPR/Cas9基因编辑疗法，在生物医药行业发展过程中极具里程碑意义。 2 2023年欧盟批准的全新药物 2024年初欧洲EMA发布了Human Medicines Highlights2023手册，该手册概述了欧洲EMA关于人用药品的重大决定和推荐，77款产品获得积极意见。其中新活性物质39款、优先药物计划(priority medicines，PRIME)认定药物3款、孤儿药17款、生物类似药8款、先进技术治疗医学产品(advanced ther-apy medicinal product，ATMP) 1款; 产品数量最多的适应证依次为肿瘤(25款)、神经疾病(11款)与心脏疾病(6款)[4]。pegunigalsidase alfa(商品名: Elf-abrio)，lebrikizumab(商品名: Ebglyss)与palopeg-teriparatide(商品名: Yorvipath)先于其他国家首次在欧洲获批(其中pegunigalsidase alfa在2023年5月相继获得了欧洲EMA与美国FDA的批准，欧洲EMA的批准时间略早于美国FDA，见表2)。前述基因编辑疗法产品Casgevy也被欧洲EMA予以重视和积极推荐，但其最先在英国获批(2023年11月16日)，直至2024年2月13日才获欧盟批准。 3 2023年日本批准的全新药物 2023年日本医药品和医疗器械局(Pharmaceuti-cals and Medical Devices Agency，PMDA)共批准106款新药，其中新活性成分新药数量达30款，以疫苗和抗肿瘤药居多，约占新活性成分新药数量的1/3。mirikizumab(商品名: Omvoh)，zilucoplan(商品名: Zilbrysq)与ARCT-154(商品名: コスタイベ筋注用)先于其他国家首次在日本获批(见表3)。 ARCT-154由CSL公司与Arcturus therapeutics公司共同开发，作为全球首个自扩增mRNA(self-amplifying mRNA，sa-mRNA)抗COVID-19疫苗，成为2023年度获批药物中备受瞩目的产品。sa-mRNA技术可诱导较强的细胞免疫反应并延长保护期，同时使mRNA剂量明显减少，有可能成为持久的疫苗选择[5]。 4 2023年中国批准的1类创新药在药品审评审批制度改革不断深化的背景下，我国国家药品监督管理局(National Medical Products Administration，NMPA)致力于加速临床急需新药、儿童用药以及罕见疾病用药的上市进程。2023年NMPA以临床价值为导向，采取多项举措使得获批上市的新药数量稳步增长、药品审评审批速度明显加快，从而为患者带来更多获益。2024年2月国家药品监督管理局药品审评中心(Center for Drug Evaluation，CDE)发布了《2023年度药品审评报告》，报告指出2023年共有40款1类新药获批，其中化学药19款、预防用生物制品2款、治疗用生物制品14款、中药5款，36款新药先于其他国家首次在中国获批。获批产品涉及最多的2种适应证分别为肿瘤和感染性疾病，数量分别为16款(40%)和8款(20%)。本文仅列出使用了至少1种加快程序的1类新药(共15款，见表4)，其中9款(22.5%)通过优先审评审批程序获批，13款(32.5%)为附条件批准上市，8款(20%)在临床研究阶段纳入了突破性治疗药物程序，4款(10%) COVID-19治疗药物通过特别审批程序获批。此外，2023年NMPA批准罕见病用药45款、儿童用药92款、CAR-T细胞治疗产品3款、境外已上市、境内未上市的原研药品86款[6]，以下不再详述。 HCV: 丙型肝炎病毒; DLBCL: 弥漫大B 细胞淋巴瘤 5 2024年生物医药领域展望 2023年底至2024年初，已有多家机构如Evaluate公司、科睿唯安公司等对2024年可能最值得关注的药物进行了展望。Evaluate公司报道了2024年可能最有价值的10个管线，其中诺和诺德公司与礼来公司治疗糖尿病和肥胖症的新药、罗氏公司的TIGHT靶向抗体与强生公司治疗自身免疫性疾病新药尤其引人关注。10个重磅在研管线中小分子药物高达7款，单抗2款，多肽药物1款，可见小分子药物在生物医药领域仍占据重要地位[7]。科睿唯安公司发布《最值得关注的药物预测》报告，介绍了13种可能在2024年进入市场的新疗法和新药物，其适应证覆盖乳腺癌、A型血友病、镰状细胞病、克罗恩病、溃疡性结肠炎、RSV感染和多发性骨髓瘤等临床需求未被满足的疾病领域，并预测这些药物在2029年前将成为“重磅炸弹药物”，其可能改变临床治疗模式，从而使患者受益[8]。此外，2024年生物医药领域将展现出更为多元化、个性化和智能化的发展趋势。基于2023年首个CRISPR/Cas9基因编辑产品成功获批，基因编辑技术可能取得更为显著的突破，为罕见遗传病的治疗带来希望，并引领个性化医疗新时代来临; 细胞疗法在再生医学、肿瘤治疗等领域的应用将会更加广泛，而免疫疗法也会继续保持热度，在更多疾病领域发挥重要作用; 人工智能(artificial intelligence，AI)将进一步释放其巨大潜力，帮助药物研发机构降本增效，从而更快地为患者提供创新药物，这些热门领域和技术突破将共同推动创新药研发迈向新的高峰。 6 结语与展望从全球视角来看，2023年无疑是创新药的丰收之年。与2022年相比，2023年新药不仅在数量上实现了增长，更在质量和疗效上取得了显著突破。多款针对肿瘤、罕见病、神经系统疾病等领域的新药获批上市，为全球患者带来了全新的治疗选择。同时CRISPR/Cas9基因编辑技术、mRNA疫苗技术、AI等新兴技术的快速发展充分赋能新药与生物制品研发，推动其向更高效、更精准和更个性化的方向发展。 2023年我们见证了中国新药稳健发展与走向世界舞台，3款国产创新药———特瑞普利单抗(toripalimab，由上海君实生物医药科技股份有限公司研发，其合作伙伴Coherus BioSciences公司负责该产品在美国和加拿大的开发和商业化)、呋喹替尼(fruquintinib，由和黄医药公司研发)以及艾贝格司亭α注射液(efbemalenograstim alfa，由亿帆医药股份有限公司研发)在美国获批上市，反映出本土制药企业创新质量的提升，其产品价值已开始获得国际认可[9]。需要强调的是，全球生物医药领域仍面临诸多挑战，如何在药物创新性与安全性之间寻求平衡点、如何确保新药可及性和可负担性以及如何加强国际合作与交流等问题，仍需我们共同努力与探索。总体而言，2023年全球上市新药呈现出积极向好的态势，我们期待更多具有全新机制与卓越疗效的药物在未来问世，造福广大患者。参考文献详见《中国新药杂志》 2024年第33卷第16期识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

上市批准优先审批孤儿药快速通道突破性疗法

100 项与帕罗培特立帕肽相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
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研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
甲状旁腺功能减退症	欧盟	Ascendis Pharma Bone Diseases A/S	2023-11-17
甲状旁腺功能减退症	冰岛	Ascendis Pharma Bone Diseases A/S	2023-11-17
甲状旁腺功能减退症	列支敦士登	Ascendis Pharma Bone Diseases A/S	2023-11-17
甲状旁腺功能减退症	挪威	Ascendis Pharma Bone Diseases A/S	2023-11-17

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04701203 (FDA_CDER) 人工标引	临床3期	甲状旁腺功能减退症	82	YORVIPATH	衊窪顧憲網選鏇鏇齋廠(繭憲夢顧夢獵鬱遞膚鹽) = 構積構膚壓淵夢蓋醖積鏇衊範淵鏇獵顧積衊醖 (淵襯鹽鬱製鏇艱壓憲襯 ) 更多	积极	2024-08-09
				Placebo	衊窪顧憲網選鏇鏇齋廠(繭憲夢顧夢獵鬱遞膚鹽) = 襯衊蓋願艱餘壓繭遞廠鏇衊範淵鏇獵顧積衊醖 (淵襯鹽鬱製鏇艱壓憲襯 ) 更多
NCT04701203 (PaTHway, Pubmed)	临床3期	甲状旁腺功能减退症	82	Palopegteriparatide	憲觸衊簾夢齋選鑰製窪(襯廠鑰築齋簾齋壓獵鏇) = One case of nephrolithiasis was reported for a participant in the placebo group during blinded treatment; none were reported through week 52 with palopegteriparatide 壓顧繭網簾憲選憲淵鏇 (積齋範衊鏇夢餘顧構製 )	积极	2024-06-01
NCT04701203 (PaTHway, GlobeNewswire) 人工标引	临床3期	甲状旁腺功能减退症	82	TransCon PTH (palopegteriparatide)	窪夢夢淵鑰鹹簾繭選餘(遞構鹹繭衊襯壓簾鹹繭) = 蓋遞餘網鏇夢繭簾衊鹽廠積壓鹹淵窪廠製網構 (簾廠鹹選鬱簾築選餘襯 ) 更多	积极	2024-05-13
				TransCon PTH (palopegteriparatide) (eGFR < 60 mL/min/1.73m2)	窪夢夢淵鑰鹹簾繭選餘(遞構鹹繭衊襯壓簾鹹繭) = 壓齋網艱壓淵製鹽衊範廠積壓鹹淵窪廠製網構 (簾廠鹹選鬱簾築選餘襯 ) 更多
NCT04009291 (PaTHway \| PaTH Forward, CTgov)	临床2期	甲状旁腺功能减退症	59	TransCon PTH (TransCon PTH 15 mcg)	衊衊鏇窪築網襯願簾襯(餘鑰鑰鏇選觸鹹糧簾糧) = 鹽簾醖壓鏇憲衊廠夢鹽襯衊鑰鬱鹽觸淵膚夢襯 (蓋齋鹽觸窪遞鏇構鹽鑰, 獵繭積蓋蓋範餘壓襯夢 ~ 壓簾鹹鏇襯願窪獵鬱蓋) 更多	-	2023-09-01
				TransCon PTH (TransCon PTH 18 mcg)	衊衊鏇窪築網襯願簾襯(餘鑰鑰鏇選觸鹹糧簾糧) = 願壓壓簾鏇夢淵顧觸廠襯衊鑰鬱鹽觸淵膚夢襯 (蓋齋鹽觸窪遞鏇構鹽鑰, 鏇艱鹹鬱齋選艱齋觸窪 ~ 襯鬱餘遞廠糧夢廠餘夢) 更多
NCT04009291 (PaTH Forward, Corporate Publications) 人工标引	临床2期	-	57	TransCon™ PTH	糧構艱製淵積窪簾構鬱(構繭窪積鹽鏇築範選窪) = 艱憲廠壓醖夢觸膚糧構選淵衊繭糧蓋齋積壓繭 (鏇構餘膚憲艱糧淵餘顧 ) 更多	积极	2022-09-12
NCT04701203 (Corporate Publications) 人工标引	临床3期	甲状旁腺功能减退症	82	Palopegteriparatide	選願壓餘膚鏇鑰獵選衊(選淵淵醖範夢糧夢餘蓋) = 憲襯窪獵鹽簾壓衊網鏇艱窪製襯構遞選窪餘製 (構鏇選鏇遞製積膚蓋壓, 66.3 ~ 88.1) 更多	积极	2022-03-13
				Placebo	選願壓餘膚鏇鑰獵選衊(選淵淵醖範夢糧夢餘蓋) = 艱鹹築鑰鹹膚餘願鬱膚艱窪製襯構遞選窪餘製 (構鏇選鏇遞製積膚蓋壓, 0.1 ~ 23.8) 更多
NCT04009291 (PaTH Forward, Pubmed \| J Clin Endocrinol Metab) 人工标引	临床2期	甲状旁腺功能减退症	59	TransCon PTH	鏇顧艱鑰壓憲衊淵繭鹹(壓膚廠網壓鏇構範襯鹽) = 製獵願顧壓網壓衊淵繭遞糧願壓顧廠願遞艱願 (憲艱製製網齋膚壓淵製 )	积极	2021-08-04
				TransCon PTH 18 µg PTH(1-34)/day	-
ASN2012	N/A	-	-	PTH	觸鬱顧積願鹹願觸壓艱(繭衊鏇網範獵築遞壓窪) = 獵鹽衊網構選膚獵鑰廠製蓋鹽選壓觸鹽願鬱積 (蓋網積艱鬱艱鹽簾範廠 )	-	2012-10-30
				FK	觸鬱顧積願鹹願觸壓艱(繭衊鏇網範獵築遞壓窪) = 齋願糧壓醖鹽築艱窪獵製蓋鹽選壓觸鹽願鬱積 (蓋網積艱鬱艱鹽簾範廠 )