First inves­ti­ga­tional prod­uct being rec­om­mended for Break­­through Therapy Desig­na­tion in China

{{image}}Somerset, NJ (Press Release) – Legend Bio­tech Corpo­ra­tion (NASDAQ:LEGN) an­nounced to­day that the China Center for Drug Evaluation, National Medical Products Admin­istra­tion (CDE, NMPA) has rec­om­mended Break­­through Therapy Desig­na­tion (BTD) for ciltacabtagene autoleucel (cilta-cel; LCAR-B38M CAR-T cells), an inves­ti­ga­tional B-cell maturation an­ti­gen (BCMA) targeted chi­meric an­ti­gen re­cep­tor (CAR) T-cell ther­apy being studied for the treat­ment of adults with re­lapsed or re­frac­tory mul­ti­ple myeloma (RRMM).

The BTD for cilta-cel (LCAR-B38M CAR-T cells) is based on the on­go­ing Phase 2 CARTIFAN-1 study being con­ducted in China (MMY2002, NCT03758417, CTR20181007), the on­go­ing Phase 1b/2 CARTITUDE-1 study of cilta-cel (JNJ-4528) being con­ducted in the US (MMY2001, NCT03548207) and Japan and the Phase 1, first-in-human LEGEND-2 study con­ducted in China (NCT03090659). Ciltacabtagene autoleucel (cilta-cel) refers to both LCAR-B38M CAR-T cells and JNJ-4528. LCAR-B38M CAR-T cell identifies the inves­ti­ga­tional prod­uct being studied in China and JNJ-4528 identifies the inves­ti­ga­tional prod­uct being studied out­side of China, both of which are rep­re­sentative of the same CAR-T cell ther­apy.

The BTD pro­ce­dure is part of the recently revised Drug Reg­is­tra­tion Regulation which went into effect on July 1, 2020. The BTD process is de­signed to expedite the de­vel­op­ment and re­view of ther­a­pies that are in­tended for treat­ment of serious dis­eases for which there is no existing treat­ment and where pre­lim­i­nary evi­dence in­di­cates ad­van­tages of the ther­apy over avail­able treat­ment op­tions.¹ Cilta-cel is the first prod­uct that has been rec­om­mended for BTD in China.² As per the work­ing pro­ce­dure for BTD (2020 No.82) issued by NMPA on July 8, 2020, CDE had com­pleted the re­view and rec­om­mended to grant the BTD on August 4th, and BTD will be granted after 5 work­ing days of pub­licity period (August 5 to 12) on the CDE website.

In De­cem­ber 2017, Legend Bio­tech entered into a world­wide col­lab­o­ration and license agree­ment with Janssen Bio­tech, Inc., one of the Janssen Pharma­ceu­tical Com­panies of John­son & John­son, to jointly de­vel­op and com­mer­cial­ize cilta-cel in patients with mul­ti­ple myeloma. Cilta-cel is a structurally dif­fer­en­ti­ated CAR-T cell ther­apy con­taining a 4-1BB co-stimulatory domain and two BCMA-targeting single domain anti­bodies de­signed to confer avidity.

“Breakthrough desig­na­tion recom­men­da­tion by the China CDE of NMPA rep­re­sents an im­por­tant regu­la­tory mile­stone in the con­tinued de­vel­op­ment of cilta-cel in mul­ti­ple myeloma patients in China,” said Frank Zhang, PhD, CEO of Legend Bio­tech. “Legend, in col­lab­o­ration with Janssen, will con­tinue to ad­vance this inves­ti­ga­tional ther­apy in China and globally.”

Previously, the fol­low­ing regu­la­tory desig­na­tions have been granted to Janssen for cilta-cel:

• In July 2020, the Korea Ministry of Food and Drug Safety granted orphan drug desig­na­tion.³
• In June 2020, the Japan Ministry of Health, Labor and Welfare granted orphan drug desig­na­tion.⁴
• In Feb­ru­ary 2020, the Euro­pean Com­mis­sion granted orphan desig­na­tion.⁵
• In De­cem­ber 2019, the U.S. Food and Drug Admin­istra­tion (FDA) granted Break­­through Therapy Desig­na­tion.⁶
• In April 2019, the Euro­pean Medicines Agency granted Janssen a PRIME (PRIority MEdicines) desig­na­tion.⁷
• In Feb­ru­ary 2019, the FDA granted Janssen orphan drug desig­na­tion for the treat­ment of mul­ti­ple myeloma.⁸

About the Clinical De­vel­op­ment Program

CARTIFAN-1

The Phase 2 CARTIFAN-1 con­firmatory trial (MMY2002, NCT03758417, CTR20181007) is being con­ducted in China to fur­ther eval­u­ate cilta-cel (LCAR-B38M CAR-T cells) in patients with RRMM who have re­ceived at least 3 prior lines of ther­apy and have re­ceived a pro­te­a­some in­hib­i­tor (PI) and an immuno­modu­la­tory drug (IMiD®); and doc­u­mented dis­ease pro­gres­sion within 12 months of start­ing the most recent ther­apy.⁹

CARTITUDE-1

Cilta-cel (JNJ-4528) is cur­rently being in­ves­ti­gated in the Phase 1b/2 CARTITUDE-1 (MMY2001, NCT03548207) pivotal study con­ducted in US and Japan for the treat­ment of patients with mul­ti­ple myeloma who have re­ceived at least 3 prior lines of ther­apy or are double re­frac­tory to a PI and IMiD®; re­ceived a PI, an IMiD and anti-CD38 anti­body; and doc­u­mented dis­ease pro­gres­sion within 12 months of start­ing the most recent ther­apy.¹⁰

CARTITUDE-2

The global, multi-cohort Phase 2 CARTITUDE-2 (MMY2003, NCT04133636) study, cilta-cel (JNJ-4528) is actively recruiting patients with mul­ti­ple myeloma in var­i­ous clin­i­cal settings. This study is being con­ducted to eval­u­ate the over­all minimal residual dis­ease (MRD) neg­a­tive rate of par­tic­i­pants who re­ceive JNJ-4528 to fur­ther explore ef­fi­cacy and safety in earlier patient pop­u­la­tions.¹¹

CARTITUDE-4

The global, Phase 3 CARTITUDE-4 (MMY3002, NCT04181827) study, cilta-cel (JNJ-4528) is actively recruiting patients with mul­ti­ple myeloma who have re­ceived 1-3 prior lines of ther­apy in­clud­ing a PI and IMiD and are re­frac­tory to lena­lido­mide. The study is being con­ducted to eval­u­ate the ef­fi­cacy of JNJ-4528 com­pared to stan­dard ther­a­pies7 in­clud­ing dara­tu­mu­mab, poma­lido­mide and low-dose dexa­meth­a­sone (DPd) or poma­lido­mide, bor­tez­o­mib and low-dose dexa­meth­a­sone (PVd).¹²

LEGEND-2

LEGEND-2 (NCT03090659) is an on­go­ing, Phase 1, single-arm, open-label, first-in-human, study of 74 patients being con­ducted at four participating hos­pi­tals in China eval­u­ating the ef­fi­cacy and safety of LCAR-B38M CAR-T cells for the treat­ment of patients with re­lapsed or re­frac­tory mul­ti­ple myeloma.¹³

About Multiple Myeloma

Multiple myeloma is an incurable blood can­cer that starts in the bone mar­row and is char­ac­ter­ized by an excessive pro­lif­er­a­tion of plasma cells.¹⁴

Although treat­ment may re­­sult in remission, unfortunately, patients will most likely relapse as there is cur­rently no cure.¹⁵ Re­frac­tory mul­ti­ple myeloma is when a patient’s dis­ease is non-responsive or progresses within 60 days of their last ther­apy.^16,17 Re­lapsed myeloma is when the dis­ease has re­turned after a period of initial, partial or com­plete remission and does not meet the definition of being re­frac­tory.¹⁸ While some patients with mul­ti­ple myeloma have no symp­toms at all, most patients are diag­nosed due to symp­toms that can in­clude bone prob­lems, low blood counts, cal­cium elevation, kidney prob­lems or in­fec­tions.¹⁹ Patients who relapse after treat­ment with stan­dard ther­a­pies, in­clud­ing protease in­hib­i­tors and immuno­modu­la­tory agents, have poor prognoses and few treat­ment op­tions avail­able.²⁰

About Legend Bio­tech

Legend Bio­tech is a global clin­i­cal-stage bio­pharma­ceu­tical com­pany engaged in the dis­cov­ery and de­vel­op­ment of novel cell ther­a­pies for on­col­ogy and other in­di­ca­tions. Our team of over 700 em­ploy­ees across the United States, China and Europe, along with our dif­fer­en­ti­ated tech­nology, global de­vel­op­ment and manu­fac­tur­ing strategies and ex­per­tise, provides us with the strong po­ten­tial to dis­cov­er, de­vel­op and com­mer­cial­ize best-in-class cell ther­a­pies for patients in need.

We are engaged in a stra­te­gic col­lab­o­ration with Janssen Bio­tech to de­vel­op and com­mer­cial­ize our lead prod­uct can­di­date, cilta-cel, an inves­ti­ga­tional BCMA-targeted CAR-T cell ther­apy for patients living with mul­ti­ple myeloma. This can­di­date is cur­rently being studied in reg­is­tra­tional clin­i­cal trials.

To learn more about Legend Bio­tech, visit us on LinkedIn, or on Twitter @LegendBiotech or at www.legendbiotech.com.

Cautions Concerning Forward-Looking State­ments

This press re­lease con­tains “forward-looking state­ments” within the meaning of The Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995 relating to the business of Legend Bio­tech Corpo­ra­tion, in­clud­ing ex­press or im­plied dis­cus­sions re­gard­ing prod­uct de­vel­op­ment, the po­ten­tial ben­e­fits and treat­ment im­pact of LCAR-B38M CAR-T cells/JNJ-4528, and the regu­la­tory ap­prov­al process for these prod­uct can­di­dates. Such for­ward-looking state­ments reflect the cur­rent views of Legend’s man­age­ment re­gard­ing future events, and in­volve known and un­known risks, un­cer­tainties and other factors that may cause actual re­­sults to be ma­teri­ally dif­fer­en­t from any future re­­sults, per­for­mance or achieve­ments ex­pressed or im­plied by such state­ments. Actual re­­sults may differ ma­teri­ally from those in­di­cated by such for­ward-looking state­ments as a re­­sult of var­i­ous im­por­tant factors, in­clud­ing, among other things, un­cer­tainties in­volved in the de­vel­op­ment of new pharma­ceu­tical prod­ucts; un­ex­pected clin­i­cal trial re­­sults, in­clud­ing addi­tional analysis of existing clin­i­cal data or un­ex­pected new clin­i­cal data; un­ex­pected regu­la­tory actions or delays or gov­ern­ment reg­u­la­tion generally; Legend’s ability to obtain or main­tain pat­ent or other pro­pri­e­tary in­tel­lec­tual prop­er­ty pro­tec­tion, in­clud­ing the un­cer­tainties in­volved in the U.S. lit­i­ga­tion process; com­pe­ti­tion in general; gov­ern­ment, industry, and general pub­lic pricing and other political pres­sures, and the other factors discussed in the “Risk Factors” section of Legend Bio­tech’s pros­pectus filed with the Se­cu­ri­ties and Ex­change Com­mis­sion on June 8, 2020. Any for­ward-looking state­ments con­tained in this press re­lease speak only as of the date hereof, and Legend Bio­tech spe­cif­i­cally disclaims any obli­ga­tion to up­date any for­ward-looking state­ment, whether as a re­­sult of new in­for­ma­tion, future events or other­wise.

References

1. China Drug Reg­is­tra­tion Regulation: http://www.gov.cn/gongbao/content/2020/content_5512563.htm
2. Proposed Break­­through Therapy Type Announcement: http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=26. Accessed August 2020
3. Korea Ministry of Food and Drug Safety. https://www.mfds.go.kr/brd/m_76/view.do?seq=14749. Accessed August 2020.
4. Japan Ministry of Health, Labor and Welfare. https://www.mhlw.go.jp/hourei/doc/tsuchi/T200629I0030.pdf. Accessed August 2020.
5. European Medicines Agency. Public summary of opinion on orphan desig­na­tion. Available at: https://www.ema.europa.eu/en/documents/orphan-designation/eu/3/20/2252-public-summary-positive-opinion-orphan-designation-autologous-human-t-cells-genetically_en.pdf. Accessed August 2020.
6. Legendbiotech.com. U.S. Food and Drug Admin­istra­tion Grants Break­­through Therapy Desig­na­tion for JNJ-68284528, an Inves­ti­ga­tional BCMA CAR-T Cell Therapy. Available at: https://www.legendbiotech.com/pdf/JNJ4528_Breakthrough_Therapy_Designation_Release.pdf. Accessed August 2020.
7. Legendbiotech.com. Euro­pean Medicines Agency Grants Janssen PRIME Desig­na­tion for JNJ-68284528 (LCAR-B38M), an Inves­ti­ga­tional BCMA CAR-T Therapy Discovered by Legend Biotech. Available at: https://www.legendbiotech.com/pdf/Legend_LCAR_PRIME_Designation_Press%20Release_4-1-2019.pdf. Accessed August 2020.
8. Accessdata.fda.gov. U.S. Food & Drug Admin­istra­tion. Available at: https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=20186721. Accessed August 2020.
9. CARTIFAN-1 (NCT03758417). Available: https://clinicaltrials.gov/ct2/show/NCT03758417. Accessed August 2020.
10. CARTITUDE-1 (NCT03548207). Available: https://clinicaltrials.gov/ct2/show/NCT03548207. Accessed August 2020.
11. CARTITUDE-2 (NCT04133636). Available: https://clinicaltrials.gov/ct2/show/NCT04133636. Accessed August 2020.
12. CARTITUDE-4 (NCT041818270. Available: https://clinicaltrials.gov/ct2/show/NCT04181827. Accessed August 2020.
13. LEGEND-2 (NCT03090659). Available: https://clinicaltrials.gov/ct2/show/NCT03090659. Accessed August 2020.
14. American Society of Clinical Oncology. Multiple myeloma: in­tro­duc­tion. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction. Accessed August 2020
15. Abdi J, Chen G, Chang H, et al. Drug re­sis­tance in mul­ti­ple myeloma: latest findings and new concepts on molecular mech­a­nisms. Oncotarget. 2013;4:2186–2207.
16. National Cancer In­sti­tute. NCI dictionary of can­cer terms: re­frac­tory. Available: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=350245. Accessed August 2020.
17. Richardson P, Mitsiades C, Schlossman R, et al. The treat­ment of re­lapsed and re­frac­tory mul­ti­ple myeloma. He­ma­tol­ogy Am Soc Hematol Educ Program. 2007:317-23.
18. National Cancer In­sti­tute. NCI dictionary of can­cer terms: re­lapsed. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=45866. Accessed August 2020.
19. American Cancer Society. Multiple myeloma: early detection, diag­nosis and staging. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8740.00.pdf. Accessed August 2020.
20. Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of pro­gres­sion and sur­vival in mul­ti­ple myeloma relapsing after ther­apy with IMiDs and bor­tez­o­mib: a multi­center inter­na­tional myeloma work­ing group study. Leukemia. 2012;26:149-57.

Source: Legend Bio­tech.