The following story appeared on 7NEWS August 2023.
When nature delivers new medicine: Our soft tissue sarcoma therapy Yondelis® (trabectedin) has this month been listed on the Pharmaceutical Benefits Scheme for patients with advanced liposarcoma and leiomyosarcoma, but you may be surprised where scientists originally sourced this novel compound.
Singapore, 8 May 2023: Independent biopharmaceutical company Specialised Therapeutics Asia (ST) is pleased to announce that a new therapy to treat rare gastrointestinal stromal tumours (GIST) shown to improve survival has been approved for use in Singapore.
The therapy, QINLOCK (ripretinib) is now approved by the Health Sciences Authority (HSA) “for the treatment of adult patients with advanced gastrointestinal stromal tumours (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib, sunitinib, and regorafenib”.
Singapore-based senior consultant in medical oncology Dr Richard Quek said QINLOCK represented a major treatment advancement for patients with advanced GIST.
“Since 2013, despite multiple attempts and studies, no therapy was shown to be effective for 4th line GIST patients whose cancers have progressed on existing treatment, until the discovery of QINLOCK,” Dr Quek said.
In the pivotal INVICTUS study that led to QINLOCK’s approval, QINLOCK was shown to significantly delay cancer progression.
“This approval in Singapore clearly provides an opportunity for us to improve the outcomes of our GIST patients who are refractory to the current existing treatment.”
QINLOCK is an oral medication used to treat GIST in people who have received at least three prior treatments. It belongs to a drug class called tyrosine kinase inhibitors and works by blocking specific tumour proliferation pathways.2
A pivotal Phase 3 clinical trial of QINLOCK – the INVICTUS study – demonstrated that QINLOCK was able to significantly reduce the risk of disease progression by 85% (hazard ratio of 0.15, p<0.0001) with a median progression-free survival of 6.3 months in patients administered QINLOCK, compared to 1.0 month in the placebo arm.1 QINLOCK was associated with clinically meaningful overall survival of 15.1 months vs 6.6 months and reduced the risk of death by 64% (hazard ratio of 0.36). The objective response rate by Blinded Independent Central Review using modified Response Evaluation Criteria in Solid Tumors (RECIST) was 9.4% with QINLOCK vs 0.0% with placebo (p=0.0504).1,3
In addition, in a long-term follow up analysis of the INVICTUS trial, patients in the QINLOCK arm demonstrated a median overall survival of 18.2 months compared to 6.3 months in the placebo arm and reduced the risk of death by 59% (hazard ratio of 0.41).The objective response rate was 11.8% with QINLOCK vs 0.0% with placebo.3
ST Chief Executive Officer Carlo Montagner said the Singapore approval followed the recent approval of QINLOCK in New Zealand, as well as regulatory and reimbursement approval in Australia.
“Achieving these critical regulatory milestones is testament to the dedication of our regulatory teams to make QINLOCK available to all eligible patients in Singapore who are impacted by this rare gastrointestinal cancer.”
ST commercialises QINLOCK in Singapore under an exclusive distribution agreement from US based Deciphera Pharmaceuticals.
Further Inquiries can be directed to ST Senior Manager Communications and Corporate Affairs Emma Power on + 65 31589910 epower@stbiopharma.com
About GIST
Gastrointestinal stromal tumour (GIST) is a cancer affecting the digestive tract or nearby structures within the abdomen, most often presenting in the stomach or small intestine. GIST growth usually begins in the connective tissue in the wall of the affected organ and grows outwards. The common location of GIST is in the stomach (50 to 60%) and small intestines (30 to 40%) but can occur in any site in the digestive system. Other possible GIST sites are the oesophagus, rectum, and colon. GIST cases are rare and estimated to cause between 0.1% and 3% of GI cancer. The risk of GIST diagnosis increases with age, with GIST incidence peaking among people in their fifties and sixties.4
About QINLOCK (ripretinib)
QINLOCK is a switch-control tyrosine kinase inhibitor that was engineered to broadly inhibit KIT and PDGFRA mutated kinases by using a dual mechanism of action that regulates the kinase switch pocket and activation loop. QINLOCK inhibits primary and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18 involved in GIST, as well as the primary exon 17 D816V mutation. QINLOCK also inhibits primary PDGFRA mutations in exons 12, 14, and 18, including the exon 18 D842V mutation, involved in a subset of GIST.5,6
About Specialised Therapeutics
Headquartered in Singapore, Specialised Therapeutics (ST) is an international biopharmaceutical company established to commercialise new therapies and technologies to patients in Australia, New Zealand and across South-East Asia. ST and its regional affiliates collaborate with leading global pharmaceutical and diagnostic companies to bring novel, innovative and life-changing healthcare solutions to patients affected by a range of diseases. Our mission is to provide therapies that would otherwise not be available to communities in our regions. The company’s broad therapeutic portfolio currently includes novel agents in oncology, haematology, neurology, ophthalmology and supportive care. Additional information can be found at www.stbiopharma.com
About the INVICTUS Phase 3 Study
INVICTUS is a Phase 3 randomised, double-blind, placebo-controlled, international, multicenter clinical study evaluating the safety, tolerability, and efficacy of QINLOCK compared to placebo in patients with advanced GIST whose previous therapies have included at least imatinib, sunitinib, and regorafenib. Patients were randomized 2:1 to either 150 mg of QINLOCK once daily (n=85) or placebo (n=44). The primary efficacy endpoint was progression-free survival (PFS) as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST). The median PFS in the study was 6.3 months in the QINLOCK arm compared to 1.0 month in the placebo arm and significantly reduced the risk of disease progression or death by 85% (hazard ratio of 0.15, p<0.0001) compared to placebo.1 Secondary endpoints included Objective Response Rate (ORR) as determined by independent radiologic review using modified RECIST and Overall Survival (OS). QINLOCK demonstrated an ORR of 9.4% compared with 0% for placebo (p=0.0504), which was not statistically significant.1 QINLOCK demonstrated a median OS of 15.1 months compared to 6.6 months in the placebo arm and reduced the risk of death by 64% (hazard ratio of 0.36).1 In a long-term follow up of 19 months after the primary analysis, QINLOCK also demonstrated a median OS of 18.2 months compared to 6.3 months in the placebo arm and reduced the risk of death by 59% (hazard ratio of 0.41).3 The most common (>2%) grade 3 or 4 treatment related adverse events in the QINLOCK group included lipase increase (5%), hypertension (4%), fatigue (2%), and hypophosphataemia (2%); and in the placebo group, anaemia (7%), fatigue (2%), diarrhoea (2%), decreased appetite (2%), dehydration (2%), hyperkalaemia (2%), acute kidney injury (2%), and pulmonary oedema (2%).1,4
References
Singapore, 9 September 2021: A globally regarded sarcoma therapy that has been shown to improve progression free survival1 is now being re-introduced in key regions of South-East Asia by independent pharmaceutical company Specialised Therapeutics Asia (STA).
The compound YONDELIS® (trabectedin) will be available to advanced sarcoma patients via their treating oncologists in Singapore, Malaysia and Brunei, following a license agreement between STA and its international pharmaceutical partner, PharmaMar S.A.
YONDELIS has been approved in Singapore, Malaysia and Brunei since 2009 and was previously provided to patients in these regions under a separate pharmaceutical arrangement with former product licensee, Janssen Products, L. E. Full marketing authorisation has now been formally transferred to STA.
YONDELIS – which has been shown to improve progression-free survival when used subsequent to anthracycline-based therapy for patients with unresectable or metastatic liposarcoma (LPS) or leiomyosarcoma (LMS)1 – is approved in Singapore and has been available to patients in the United States since 2015,2 and in Europe since 2007.3
Malaysian sarcoma specialist Dr Aminudin Rahman Bin Mohd Mydin, Consultant Clinical Oncologist at the KPJ Damansara Specialist Hospital, welcomed the renewed availability of YONDELIS for appropriate patients in South East Asia.
Dr Aminudin commented: “This is exciting news. YONDELIS is an established therapy that has already been extensively used globally to treat advanced sarcoma patients in South East Asia and globally.
“We expect that the reintroduction of this important therapy in key South East Asian regions will provide a new treatment option for many of our patients, as we strive to provide new therapy options and improve outcomes.”
STA Chief Executive Officer Mr Carlo Montagner said YONDELIS had been previously available to South East Asian patients and is recognised as a global standard of care therapy.
Mr Montagner commented: “Our company has a strong and extensive foundation in oncology and this product is a valuable inclusion to our therapeutic portfolio. We look forward to working with the sarcoma community in multiple regions of South East Asia to improve access to YONDELIS and ensure that it is considered as a new therapy option for all appropriate patients.”
STA markets YONDELIS under an exclusive license arrangement with an international partner, PharmaMar.
Ends.
Headquartered in Singapore, Specialised Therapeutics Asia Pte Ltd (STA) is an international biopharmaceutical company established to commercialise new therapies and technologies to patients throughout South East Asia, as well as in Australia and New Zealand. STA and its regional affiliates collaborate with leading global pharmaceutical and diagnostic companies to bring novel, innovative and life-changing healthcare solutions to patients affected by a range of diseases. Its mission is to provide therapies where there is an unmet need. The company’s broad therapeutic portfolio currently includes novel agents in oncology, haematology, neurology, ophthalmology and supportive care. Additional information can be found at www.stbiopharma.com
Headquartered in Madrid, PharmaMar is a biopharmaceutical company focused on oncology and committed to research and development, taking its inspiration from the sea to discover molecules with antitumor activity. It is a company seeking innovative products to provide health care professionals with new tools to treat cancer. Its commitment to patients and to research has made it a world leader in the discovery of antitumor drugs of marine origin.
PharmaMar has a pipeline of drug candidates and a robust R&D oncology program. It develops and commercializes YONDELIS® in Europe and has other clinical stage programs under development for several types of solid cancers: lurbinectedin (PM1183), PM184 and PM14.
YONDELIS® (trabectedin) is a novel, multimodal, synthetically produced antitumor agent, originally derived from the sea squirt, Ecteinascidia turbinata. The anti-cancer medicine works by preventing tumor cells from multiplying and is approved in 76 countries in North America, Europe, South America and Asia for the treatment of advanced soft-tissue sarcomas as a single-agent, and in 69 countries for relapsed ovarian in combination with DOXIL®/CAELYX® (doxorubicin HCl liposome injection).
The approval was based on the results of a pivotal phase 3, randomised, open-label controlled study which evaluated YONDELIS versus dacarbazine in over 500 patients with unresectable or metastatic liposarcoma (LPS) or leiomyosarcoma (LMS) previously treated with an anthracycline and at least one additional chemotherapy regimen. LPS and LMS are subtypes of soft tissue sarcoma (STS) and represent more than 35% of all STS cases.4
The median progression-free survival (PFS) among the YONDELIS treatment group was 4.2 months compared to 1.5 months in the dacarbazine treatment group, representing a 45% reduction in the risk of disease progression or death with YONDELIS (HR=0.55; 95% CI: 0.44 – 0.70; p<0.001).1
Among the 340 patients who received YONDELIS and were included in the safety analysis in the randomised trial, the most common (≥20%) adverse reactions were nausea (73%), fatigue (67%), vomiting (44%), constipation (36%), decreased appetite (34%), diarrhoea (34%), dyspnoea (25%), peripheral oedema (24%) and headache (23%). The most common (≥20%) laboratory abnormalities were neutropenia (49%), increased alanine transaminase (ALT) (45%), anaemia (39%), increased aspartate aminotransferase (AST) (35%), thrombocytopaenia (30%) and increased blood alkaline phosphatase (20%).1
Soft tissue sarcoma is a rare type of cancer that forms as a painless lump (tumour) in any one of the soft tissues connecting all the organs and body structures – including fat, muscle, nerves, deep skin tissue, blood vessels and the tissue surrounding joints (synovial tissue). Soft tissue sarcomas commonly develop in the thigh, shoulder and pelvis and may sometimes develop in the abdomen or chest.5
Metastatic or locally advanced STS is generally considered incurable, with the mainstay of treatment being systemic chemotherapy. For some patients with limited disease burden however, long-term remission can be achieved through a multimodality approach involving medical, surgical and radiation therapy.5
YONDELIS is a registered trademark of PharmaMar SA. YONDELIS is under license from PharmaMar SA.
Emma Power, Corporate Affairs and Communications Manager, Specialised Therapeutics Asia +65 3158 9940 or +61 419 149 525 or epower@stbiopharma.com
References:
1. Demetri G. et al. J Clin Oncol. 2016; 34(8): 786-793
2. Barone A. et al. Clin Cancer Res; 2017; 23(24): 7448-7453
3. YONDELIS (trabectedin) European Medicines Agency Summary of Product Characteristics
4. Cancer Council Victoria Fact Sheet – Soft tissue sarcoma. Available at https://www.cancervic.org.au/cancer-information/types-of-cancer/soft_tissue_cancers/soft-tissue-cancers-overview.html. Last Accessed: October 2019.
5. Bae S. et al. Clin Sarcoma Res. 2016; 6:11