New Therapy to Treat Advanced Small Cell Lung Cancer ZEPZELCA® (lurbinectedin) Approved in Singapore

Highlights:

ZEPZELCA® (lurbinectedin) is the first new therapy approved in Singapore to treat 2L metastatic small cell lung cancer (SCLC) in 20 years

ZEPZELCA provisional approval represents an important advance for adult patients whose metastatic SCLC has progressed on or after platinum-based chemotherapy

HSA and US FDA collaborated via 'Project Orbis' initiative to accelerate availability to Singapore patients

SINGAPORE,Sept. 22,2021 -- SINGAPORE patients with an aggressive form of lung cancer (metastatic small celllung cancer) can now access a new therapy that may improve outcomes.

The drug ZEPZELCA (lurbinectedin) has been provisionally approved by Singapore's Health Sciences Authority (HSA) "for the treatment of adult patients with metastatic small cell lung cancer (SCLC) who have progressed after prior platinum-containing chemotherapy".[1]

This means patients who have failed other existing treatment options will now have a further therapeutic option.

ZEPZELCA is the first new therapy approved by the HSA to treat second-line SCLC in more than two decades,and is the third oncology drug in Specialised Therapeutics (ST) portfolio to receive HSA approval.

The Singapore approval follows on from approvals by the US Food and Drug Administration (FDA) decision[2],as well as the Therapeutic Goods Administration (TGA) in Australia.[3]

Lung Cancer Oncologist and past president of Australasian Lung Cancer Trials Group Professor Paul Mitchell from the Olivia Newton-John Cancer and Wellness and Research Centre said SCLC was particularly aggressive and more than two-thirds of patients were diagnosed with extensive stage disease. He said fewer than 5% of these patients currently survived more than five years post diagnosis.[4,5]

"The new availability of ZEPZELCA will be welcomed by patients,families and the medical community,as we strive to improve patient outcomes for this disease," Professor Mitchell said.

"With this approval,we now have another option for patients who have progressed after prior platinum-based treatments. This provides an opportunity for them to continue treatment and potentially,improve outcomes."

The HSA approval of ZEPZELCA has been granted following collaboration with the US FDA via the 'Project Orbis' initiative,due to the high unmet clinical need in SCLC. It is based on monotherapy clinical data from an open-label,multi-centre,single-arm study in 105 adult platinum-sensitive and platinum-resistant patients with SCLC who had disease progression after treatment with platinum-based chemotherapy.[6]

The data,which appeared inThe Lancet OncologyMay 2020issue,demonstrated that in patients with relapsed SCLC,ZEPZELCA provided an ORR of 35% and a median duration of response of 5.3 months as measured by investigator assessment (30% and 5.1 months respectively,as measured by an independent review committee (IRC)).[6]

The provisional approval is the subject of a further confirmatory study in more than 700 patients with 2L SCLC. This study is expected to be completed in 2025.

ZEPZELCA is being made available in Singapore by independent pharmaceutical company Specialised Therapeutics under exclusive license from its international partner PharmaMar.

Specialised Therapeutics Chief Executive Officer Mr Carlo Montagner said lung cancer was the third most common cancer in Singapore,representing more than 22% of all cancer deaths. SCLC represented between 10- 15% per cent of all lung cancer diagnoses.[7,8]

"We are delighted to be able to provide a new therapy option in Singapore for patients with this difficult to treat cancer," he said.

"While patients may initially respond to traditional chemotherapy,they often experience an aggressive recurrence that is historically resistant to treatment.

"We expect that this therapy may now be an option for up to 100 Singapore patients every year and look forward to making a difference for these patients and their families."

PharmaMar president José María Fernández Sousa-Faro,PhD,said the company was delighted South-East Asian patients would now be provided access to ZEPZELCA.

"We are pleased to bring a new treatment choice to relapsed SCLC patients. "Theaccelerated approval ofZEPZELCAunderscores its potential to fill an unmet need in this often-overlooked SCLC community."

ZEPZELCA has been available in Singapore via an Early Access Program since July 2020.

About SCLC in Singapore

SCLC represents a serious condition. It is a particularly aggressive type of lung cancer related to smoking that represents approximately 10-15% of all lung cancers,accounting for more than 275,000 new cases worldwide every year.[9,10]SCLC is characterised by rapid growth,early dissemination that is often asymptomatic and with acquired resistance to drugs. SCLC is staged into limited-stage or extensive-stage disease. Limited-stage disease is potentially curable with aggressive therapy consisting of concurrent chemoradiotherapy,prophylactic cranial irradiation,and occasionally,surgery.[11,12]However,nearly two-thirds of SCLC patients have extensive-stage disease at diagnosis,which is not curable,and patients are treated with palliative intent,with a median survival of 7 to 11 months after diagnosis and with less than 5% survival at 2 years.[13,14]

Lung cancer is the third most common cancer in Singapore and represents 22.3% of all cancer deaths. Between 2014 and 2018,approximately 7,945 new cases of lung cancer were diagnosed in Singapore,with 10-15% of these classified as SCLC (between 150 and 240 new SCLC cases annually).[7,8]While the age-standardised incidence rate of all lung cancer has been in decline since the 1970's (mid-50's per 100,000 in 1968 to mid-30's per 100,000 in 2017),the five-year relative survival has seen a moderate increase to approximately 10% in 2017. Globally,the prognosis of patients with SCLC is dismal with a 5-year survival rate of less than 5% and an average overall survival period of only 2-4 months for patients not receiving any active treatment.[11,12]

Modern studies,including those of recent immunotherapies,suggest that between 40-60% of patients that receive front-line therapy will be clinically eligible for second-line therapy.[15-18] This suggests that,based on 2014-2018 lung cancer incidence figures from the Singapore Cancer registry[8],between 60 to 100 patients would be eligible for second-line SCLC treatment in Singapore.

AboutZEPZELCA®(lurbinectedin)

ZEPZELCA is an alkylating drug that binds guanine residues within DNA. This triggers a cascade of events that can affect the activity of DNA binding proteins,including some transcription factors,and DNA repair pathways,resulting in disruption of the cell cycle and eventual cell death.[1]

ZEPZELCAor injection 4 mg is a prescription medicine used to treat adults with a kind of lung cancer called small cell lung cancer (SCLC) that has spread to other parts of the body (metastatic) and who have received treatment with chemotherapy that contains platinum,and it did not work or is no longer working.ZEPZELCAis approved based on response rate and how long the response lasted. Additional studies will further evaluate the benefit ofZEPZELCAfor this use.

About the Phase II Monotherapy Trial

The Phase 2 trial ofZEPZELCA was an open-label,single-arm study,which enrolled a total of 105 SCLC patients at 26 hospitals in six European countries and theU.S.[6]In the trial,platinum-sensitive and platinum-resistant patients were treated withZEPZELCA 3.2mg/m2,administered as a 60-minute IV infusion repeated every 21 days until disease progression or unacceptable toxicity. The primary endpoint,ORR,was 35%and the median duration of response was 5.3 months as measured by investigator assessment (30% and 5.1 months respectively,as measured by an IRC).[6]ZEPZELCAwas discontinued in 1.9% of patients and was delayed in 30.5% of patients due to an adverse reaction. Dose reductions for an adverse reaction occurred in 25% of patients.[6]

About Specialised Therapeutics

Headquartered in Singapore,Specialised Therapeutics (ST) 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. 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. 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

AboutPharmaMar

Headquartered inMadrid,PharmaMaris a biopharmaceutical company,focused on oncology and committed to research and development which takes its inspiration from the sea to discover molecules with antitumor activity. It is a company that seeks innovative products to provide healthcare professionals with new tools to treat cancer.Its commitment to patients and to research has made it one of the world leaders in the discovery of antitumor drugs of marine origin.

PharmaMarhas a pipeline of drug candidates and a robust R&D oncology program. It develops and commercializes Yondelis®inEuropeand has other clinical-stage programs under development for several types of solid cancers: lurbinectedin (PM1183),PM184 and PM14. With subsidiaries inGermany,Italy,France,Switzerland,Belgium,Austriaandthe United States.PharmaMarwholly owns other companies: GENOMICA,a molecular diagnostics company;Sylentis,dedicated to researching therapeutic applications of gene silencing (RNAi). To learn more aboutPharmaMar,please visit us atwww.pharmamar.com.

References

[1].ZEPZELCA (lurbinectedin) HSA Approved Singapore Prescribing Information.

[2].ZEPZELCA (lurbinectedin) FDA Approved US Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213702s000lbl.pdf

[3].ZEPZELCA (lurbinectedin) TGA Approved Australian Prescribing Information. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2021-PI-02108-1&d=20210914172310101

[4].PDQ Adult Treatment Editorial Board. Small Cell Lung Cancer Treatment (PDQ®) Health Professional Version. Published online: May 1,2019. Available at https://www.ncbi.nlm.nih.gov/books/NBK65909/(accessed 8 October 2019)

[5].Cancer Council https://www.cancer.org.au/about-cancer/types-of-cancer/lung-cancer.html

[6]. Trigo J,Subbiah V,Besse B,et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm,open-label,phase basket trial.Lancet Oncol.2020; 21(5):645–654.

[7]. Singapore Cancer Society. https://www.singaporecancersociety.org.sg/learn-about-cancer/types-of-cancer/lung-cancer.html

[8]. Singapore Cancer Registry Annual Report 2018. https://www.nrdo.gov.sg/docs/librariesprovider3/default-document-library/scr-annual-report-2018.pdf?sfvrsn=bcf56c25_0

[9].Ferlay J,Steliarova-Foucher E,Lortet-Tieulent J,et al.Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012.Eur J Cancer2013; 49:1374-403.

[10]. Slotman B,et al: Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007; 357(7): 664 – 72

[11]. Stinchcombe TE,Gore EM. Limited-stage small cell lung cancer: current chemoradiotherapy treatment paradigms. Oncologist. 2010;15(2):187–95.

[12]. Demedts IK,Vermaelen KY,van Meerbeeck JP. Treatment of extensive-stage small cell lung carcinoma: current status and future prospects. Eur Respir J. 2010; 35(1):202–15.

[13]. Simos D,et al,Third line chemotherapy in SCLC: an international analysis. Clin Lung Cancer 2014; 15 (2): 110-8

[14]. Pelayo Alvarez M,et al. Chemotherapy versus best supportive care for extensive SCLC. Cochrane Database Syst Rev 2013; 11: CD001990

[15]. Puglisi M,et al. Treatment options for SCLC – do we have more choice? Br J Cancer 2010; 102 (4): 629-38

[16]. Paz-Ares L,Dvorkin M,Chen Y,et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised,controlled,phase 3 trial. Lancet. 2019; 394(10212):1929-1939.

[17]. Horn L,Mansfield AS,Szczęsna A,et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018; 379(23): 2220-2229.

[18]. Hanna N,Bunn PA Jr,Langer C,et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006; 24(13): 2038-2043.

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