Products

Date: 2017-12-14

Type of information: Positive opinion for the granting of a Market Authorisation in the EU

Product name: Alofisel® (Cx601 - darvadstrocel)

Compound: darvadstrocel - adipose derived allogeneic stem cell therapy

Therapeutic area: Autoimmune diseases – Inflammatory diseases - Digestive diseases

Action mechanism:

• Cell therapy. Cx601 is a suspension of expanded allogeneic adult stem cell (eASCs) product derived from human adipose (fat) tissue (expanded Adipose derived Stem Cells or eASCs) that is delivered locally in the fistula through intra-lesional injection. Cx601 is currently in Phase III of clinical development for the treatment of complex perianal fistulas in patients with Crohn's disease.
• Cx601 has been licensed to Takeda for the exclusive development and commercialization outside the US. TiGenix retains full rights to the product in the U.S. and is currently conducting a global Phase III clinical trial (ADMIRE-CD II) intended to support a future U.S. Biologic License Application.
• TiGenix retains full rights to the development of Cx601 in other indications and has identified a number of areas across fistulising disease where serious unmet medical needs exist, and which share similarities with complex perianal fistulas in Crohn's disease in terms of disease development and treatment approaches.

Company: Tigenix (Belgium)

Disease: complex perianal fistulas in patients with Crohn's disease

Latest news:

• • On December 14, 2017,  Cx601 had received a positive CHMP opinion for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn's disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy. The Company is working with its Scientific Advisory Board on the most appropriate clinical development plan for each of these indications prior to discussing with Regulators in Scientific Advice meetings.
• TiGenix is also advancing its Phase I/II clinical SEPCELL trial to evaluate Cx611 for the treatment of severe sepsis secondary to community-acquired pneumonia (sCAP) in patients who require mechanical ventilation and/or vasopressors.  A favorable safety and tolerability profile for Cx611 was demonstrated in a Phase I sepsis challenge trial completed in 2015.
• Given the focus on Cx601 and the allogeneic adipose-derived stem cell technology, TiGenix will not be investing in further R&D of its allogeneic cardiac stem cell technology and will review alternatives for further investment in this technology.
• • On November 16, 2017, Tigenix announced  that the European Medicines Agency’s (EMA) Committee for Human Medicinal Products (CHMP) has approved the company’s proposed trade name Alofisel® for Cx601, a treatment for complex perianal fistulas in patients with Crohn’s disease. The trade name Alofisel will be used from now onwards in the ongoing centralized drug approval process of Cx601 with the EMA, covering all 28 member states of the EU, plus Norway, Iceland and Lichtenstein, as well as from the time of launch following marketing authorization.
• TiGenix has also received approval from the United States Adopted Names (USAN) Council and the International Nonproprietary Names (INN) Expert Group at the World Health Organization (WHO) for the use of the nonproprietary name darvadstrocel for Cx601.
• • On June 20, 2017, Takeda and TiGenix announced that the Swiss Agency for Therapeutic Products (Swissmedic) has accepted for review the file on Cx601 to treat complex perianal fistulas in patients with Crohn's disease. Filing follows Swissmedic granting orphan drug status for Cx601 in September 2016, which recognizes the rare and debilitating nature of the disease. The marketing authorization application (MAA) for Cx601 is already under review by the EMA (See below). The Swissmedic filing submission included the Phase III ADMIRE-CD trial data for Cx601.
• • On May 31, 2017, TiGenix announced that it will submit responses to the Cx601 Marketing Authorization Application Day 180 List of Outstanding Issues (LoOI) during the month of August. The submission of the responses to the Committee for Medicinal Products for Human Use (CHMP) Day 180 LoOI is part of the standard regulatory procedure, under which on the so called Day 181 the European Medicines Agency (EMA) continues the review of a file following a clock stop. The Day 181 for the Cx601 file falls within the first week of September, which may trigger a CHMP opinion in October.
• • On March 6, 2017, TiGenix announced that it has received the Day 180 List of Outstanding Issues (LoOI) from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). The company has entered a "clock stop" period as part of the centralized review process related to the Marketing Authorization Application (MAA) for Cx601. After reviewing the LoOI, TiGenix is confident in its ability to provide detailed and clarifying responses to the CHMP and remains on track to receive a Marketing Authorization (MA) decision for Cx601 in 2017. Receipt of the MA will trigger a milestone payment from Takeda to TiGenix of Euro 15 million. The D180 LoOI is part of the EMA's official review and approval process.
• • On December 22, 2016, TiGenix announced that it has submitted its responses to the Day 120 List of Questions issued by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) as part of the centralized review process of the Marketing Authorization Application (MAA) of Cx601 for the treatment of perianal fistula in Crohn's disease patients. The company now expects to receive the  Day 180 List of Outstanding Issues in February 2017 and anticipates a decision from the EMA on Cx601 Marketing Approval during 2017.
• • On October 17, 2016, TiGenix announced that Cx601 has been granted Orphan Drug Designation status in Switzerland. This is the second orphan drug designation granted to Cx601. This decision was based on the recognition of the European Commission's Orphan Drug Designation in 2009, as well as the supporting data provided to the agency, which addressed proof of quality, efficacy and safety, as well as the rarity of the disease.
• • On March 2, 2016, TiGenix announced the submission of a centralized Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for Cx601 for the treatment of complex perianal fistulas in adult patients with Crohn's disease. Tigenix's goal is now to make its therapy  available to European patients in the second half of 2017. "The EMA filing is the culmination of the milestones set by TiGenix over the last eight months," said Eduardo Bravo CEO. "This achievement follows the completion of the ADMIRE-CD trial in August, the recently granted license to manufacture Cx601 commercially in Europe and the agreement from the FDA through a Special Protocol Assessment (SPA) on our proposal to conduct a Phase III pivotal trial in the USA. Our capacity to execute timely on these objectives reassures us about our ultimate goal of launching Cx601 in the coming years at both sides of the Atlantic."
• • On February 23, 2016, TiGenix announced that it has successfully obtained the license for commercial production of Cx601, TiGenix's product for the treatment of complex perianal fistulas in Crohn's disease patients. The manufacturing license has been issued by the Spanish Medicines Agency (AEMPS). Following the successful completion of its Phase III ADMIRE-CD clinical trial in August, the approval marks a new milestone  to bring Cx601 to European patients suffering from complex perianal fistulas.
• • On June 11, 2015, TiGenix announced that it has submitted to the European Medicines Agency (EMA) a letter of intent to file, and a request for the assignment of Rapporteur/Co-Rapporteur, for the Marketing Authorisation Application (MAA) of Cx601 in the treatment of complex perianal fistulas in patients with Crohn's disease. The letter of intent, which must be filed at least seven months prior to the submission of a MAA, initiates a process to address a number of pre-submission requirements, including the assignment of a Rapporteur and Co-Rapporteur, who are members of the Committee for Advanced Therapies (CAT), and two Co-ordinators from the Committee for Human Medicinal Products (CHMP). For advanced-therapy medicines, CAT prepares a draft opinion on the product's quality, safety and efficacy, based on which the CHMP adopts a final opinion.
• In parallel, TiGenix has submitted the request in order to be eligible for the centralised procedure for the approval of medicinal products in the European Union (EU). Cx601 falls within the mandatory scope of the procedure because it is an Advanced Therapy Medicinal Product and an Orphan-designated product.
• • On September 8, 2014, TiGenix announced  that the Paediatric Committee of the European Medicines Agency (EMA) has issued a positive opinion on the Company's Paediatric Investigation Plan (PIP) for Cx601, a locally injected stem cell product in Phase III of clinical development for the treatment of complex perianal fistulas in patients with Crohn's disease. The PIP for Cx601 consists of one open-label, multi-centre, non-comparative trial to evaluate the activity of Cx601 for the treatment of complex anal fistulas in at least 20 Crohn's disease patients aged from 4-17 years. The study will assess efficacy and safety. The primary endpoint will be remission of perianal fistulising Crohn's disease at week 24, defined as closure of all external openings that were draining at the start of the study. The study will have a follow-up period of one year. However the study will not begin before 2020, three years after Tigenix's planned launch of Cx601 in 2017.

Patents:

• • On April 8, 2015, TiGenix announced that the United States Patent and Trademark Office (USPTO) has issued US Patent 8,999,709 relating to the use of an adipose-derived stromal cell population in the treatment of fistula. The patent, entitled "Use of adipose tissue-derived stromal stem cells in treating fistula", expires in 2030 and provides coverage for the company's lead development product, Cx601, in the key US market. The issuance of this patent further strengthens TiGenix's intellectual property portfolio of 24 patent families which now includes 15 granted patents related specifically to its eASC platform. The pending and granted patents in TiGenix's intellectual property portfolio include patent families that are directed to its eASC platform; more specifically, to eASC compositions and therapeutic applications as well as to cell therapy delivery mechanisms and other eASC technology improvements.

Submission of marketing authorization application USA :

Submission of marketing authorization application UE:

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization:

UE authorization:

Favourable opinion UE: 2017-12-14

Favourable opinion USA:

Orphan status USA:

Orphan status UE: 2009-10-14

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes