Zalmoxis (nalotimagene carmaleucel) / Megapharm, TTY Biopharm, AGC Biologics - LARVOL DELTA

TK008: Efficacy Study on the Strategy of HSV-Tk Engineering Donor Lymphocytes to Treat Patients With High Risk Acute Leukemia (clinicaltrials.gov) - P3; N=92; Terminated; Sponsor: AGC Biologics S.p.A.; N=170 ➔ 92; Recruiting ➔ Terminated; EMA withdrew the marketing Authorisation at the request of AGC Biologics S.p.A (formerly MolMed S.p.A), which decided to permanently discontinue the marketing of the product for commercial reasons

Clinical • Enrollment change • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

[VIRTUAL] Market Access Landscape for Advanced Therapy Medicinal Products in the EU-5 (ISPOR-EU 2020) - "The reimbursement and pricing vary between countries as outlined below: France: 7/11 ATMPs were assessed (vs 6/10 in 2019) and 6 (vs 5 in 2019) obtained a positive reimbursement decision: three (vs 0 last year) have a public price (Yescarta, Kymriah, Alofisel)...Italy: 5/11 drugs (vs 2/10 in 2019) are reimbursed to date (Strimvelis, Holoclar, Zalmoxis, Kymriah, Yescarta)...UK: 7/11 drugs (vs 6/10 in 2019) are approved by NICE: Spherox via STA with the two CAR-Ts included in the CDF. Three technologies (Holoclar, Imlygic and Luxturna) were recommended with a simple discount Patient Access Scheme. Two ATMPs, Zynteglo and Zolgensma are currently being evaluated by NICE. CONCLUSIONS Most ATMPs are granted patient access in EU5 even though HTA bodies have imposed monitoring requirements to ensure the value reflects the price."

[VIRTUAL] Atmps Scenario across Europe, What HAS Changed and What Should WE Expect? (ISPOR-EU 2020) - "Regarding the authorised ATMPs, 5 were withdrawn from the market due to commercial reasons (the most recent case was Zalmoxis)... The arrival of CAR-Ts has initiated a profound change in ATMPs approach, confirming the great clinical expectations on these technologies. Indeed, all EU5 granted CAR-Ts access and reimbursement, despite sustainability issues related to price and organizational impact. In Italy these issues were overcome by introducing novel and ad hoc agreements and strategies."

"$MLM & Dompé: breakout only 1.5y after the deal was signed for Zalmoxis... MolMed $MLM and Dompé announce the mutual termination of the license and distribution agreement for Zalmoxis® https://t.co/B3UwgMjsFo" (@BiotechRadar)

"Disappointing End For MolMed’s Zalmoxis Cell Therapy In EU https://t.co/vKqDGkQYiY #PinkSheet" (@PharmaPinkSheet)

THE REIMBURSEMENT STATUS OF ADVANCED THERAPY MEDICINAL PRODUCTS IN EUROPE (ISPOR-EU 2019) - "RESULTS : Fourteen ATMPs were approved in Europe: Chondrocelect®, Glybera®, MACI®, Provenge®, Holoclar®, Imlygic®, Strimvelis®, Zalmoxis®, Spherox®, Alofisel®, Kymriah®, Yescarta®, Luxturna® and Zynteglo®. Conditional reimbursement is increasingly considered as useful policy to mitigate uncertainty. It allows gathering long-term evidence without delaying patient access to ATMPs."

Reimbursement

INNOVATIVE ATMPS- MARKET ACCESS AND REIMBURSEMENT DECISIONS IN THE EU5- AVAILABILITY OR NOT, THAT IS THE QUESTION... (ISPOR-EU 2019) - "OBJECTIVES: Since 2015, innovative ATMPs (Alofisel, Kymriah, Holoclar, Imlygic, Spherox, Strimvelis, Yescarta, Zalmoxis, Luxturna and Zynteglo) have been reached market authorization through the EMA. There is no difference in market access processes for ATMP therapies in comparison to standard pathways in Europe. Innovative and sustainable pricing schemes are under discussions within all payers in Europe."

Reimbursement

THE USE OF MANAGED ENTRY AGREEMENTS FOR ADVANCED THERAPIES IN EU5 (ISPOR-EU 2019) - "...RESULTS : In Italy, outcomes-based MEAs are widely used; Holoclar® and Strimvelis® are reimbursed with a payment by result agreement and Zalmoxis® has a flat cost per patient...The 2 CAR-Ts Kymriah® and Yescarta® are funded through the cancer drugs fund that allows developers to collect further clinical evidence to mitigate uncertainties...In view of the important number of ATMPs expected to reach the market, the call for innovative funding models is becoming ever louder. There is an urgent need of developing an infrastructure to harmonize and foster the use of MEAs."

ANALYSIS OF REIMBURSEMENT STATUS OF 8 APPROVED CELL AND GENE THERAPIES IN THE USA, 6 MAJOR EUROPEAN COUNTRIES, AUSTRALIA, AND JAPAN (ISPOR 2019) - " Four gene therapies (Voretigene neparvovecrzyl, Alipogene tiparvovec, Nusinersen, GSK-2696273) and four CGTs [CAR-T: Tisagenlecleucel, Axicabtagene ciloleucel, Talimogene laherparepvec, TBI-0301 (HSV-Tk)] were identified. The lack of evidence on long-term efficacy followed by the high price and impact on the budget are the main reasons for not approving reimbursement of the CGTs. Thus, new reimbursement models are necessary for financing these treatments and make them available for the patients and affordable for the health care systems."

Reimbursement

Generation of High-Titer Self Inactivated (SIN) γ-Retroviral Vectors in Stable Producer Cells (ASGCT 2019) - "Successful examples of therapies using this vector are Strimvelis, Yescarta and Zalmoxis that have been recently approved for commercialization. Vectors with the long COL7A1 cDNA (8.9 kb) had titers in transient transfections of 2 x 105IU/ml with or without WPRE, and the best stable 293Vec-Ampho clone released vectors at 9 x 105IU/ml.Thus, a simple and efficient process was established for the generation of stable 293Vec-derived retrovirus producer cells that release high-titer SIN vectors. We conclude that the stable production of SIN ?-retroviral vectors with the 293Vec platform will be a more efficient, a more reliable and a cheaper option for late stage trials and commercialization than the production in transient transfection."

"MolMed $MLM Germany confirms the reimbursement of Zalmoxis® at a price of 130,000 Euro per infusion https://t.co/aqeTzZqWGv" (@BiotechRadar)

Pricing • Reimbursement