Date: 2017-10-23
Type of information: Milestone
Compound: Cresemba® (isavuconazole)
Company: Basilea Pharmaceutica (Switzerland) Astellas Pharma (Japan)
Therapeutic area: Infectious diseases
Type agreement: development - licensing - commercialisation - promotion
Action mechanism:
- systemic antifungal agent. Isavuconazole is an intravenous and oral broad-spectrum antifungal. It has a fungicidal effect by blocking the synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of the enzyme lanosterol 14 alpha demethylase. In collaboration with Astellas Pharma Inc., isavuconazole is being investigated in phase 3 clinical studies for the treatment of severe invasive fungal infections. The drug demonstrated in-vitro and in-vivo coverage of a broad range of yeasts (such as Candida species) and molds (such as Aspergillus species) as well as in-vitro activity against less prevalent but often fatal molds including those that cause mucormycosis. In clinical studies to date, isavuconazole achieved predictable drug levels supporting reliable dosing and a switch from intravenous administration to a once-daily oral dose. The intravenous formulation of isavuconazole, which is water-soluble, does not contain potentially kidney damaging solubilizers and has the potential to be given also to patients with pre-existing renal impairment.
Disease: aspergillosis, invasive mucormycosis
Details:
- • On February 28, 2014, Basilea Pharmaceutica has announced the amendment of the isavuconazole License, Co-Development and Co-Promotion Agreement with Astellas Pharma Inc. originally executed in 2010, providing Basilea full rights to isavuconazole in all markets outside of the U.S. and Canada in return for Basilea\'s right to co-promote the product in the U.S. and Canada and its right to receive payments related to co-promotion and EU milestone payments. Through this agreement Basilea complements its global ceftobiprole rights with rights for isavuconazole in Europe, Asia and the rest of the world outside of the U.S. and Canada, providing Basilea a unique opportunity to optimize the value of two highly complementary and synergistic anti-infective drugs.
- Under the terms of the amended agreement, Astellas will remain responsible for the continued development and funding of the isavuconazole global candidemia phase 3 study. Astellas will be responsible for the regulatory filing for the primary treatment of invasive aspergillosis and invasive mucormycosis in the U.S. and Canada and will support preparation of the European filing dossier which Basilea will submit as applicant in Europe.
Basilea and Astellas will continue to coordinate their development and manufacturing activities and each company will be responsible for commercial activities in its respective territory. A transition plan for the development, manufacture and commercialization of isavuconazole outside of the U.S. and Canada is currently being developed.
- Isavuconazole recently successfully completed the phase 3 non-inferiority SECURE study in invasive aspergillosis showing significant safety advantages. In addition, isavuconazole treated patients with renal impairment and emerging molds such as mucormycosis in the open-label VITAL study, which with the SECURE study data, will form the basis of a regulatory filing in the U.S. and EU. Results from the randomized, double-blind invasive aspergillosis SECURE phase 3 study showed that isavuconazole was non-inferior to the standard-of-care, voriconazole, as assessed by the primary endpoint of all-cause mortality through day 42. Study drug-related adverse events were significantly lower in the isavuconazole group (42.4%) compared to the voriconazole group (59.8%). In addition to a potentially improved safety profile, isavuconazole, through its spectrum of activity against molds causing mucormycosis (zygomycosis) and its predictable drug exposure, has the potential to overcome a number of limitations of the current standard-of-care for the treatment of invasive mold infections.
- The open-label phase 3 VITAL study enrolled 149 patients. The study included patients with invasive fungal disease caused by emerging fungal pathogens such as Mucormycetes and patients with aspergillosis who had pre-existing renal impairment for which i.v. voriconazole can only be used with caution. VITAL study results show that day 42 all-cause mortality in renally-impaired patients with invasive aspergillosis (n = 20) was 15%. In the SECURE study, which due to the comparator did not allow for enrollment of patients with moderate or severe renal impairment, the mortality rate in patients treated with isavuconazole (n = 258) was 18.6%. In addition, day 42 all-cause mortality in VITAL study patients with confirmed mucormycosis (n = 37), which included patients refractory or intolerant to other antifungal therapies, was 37.8%, which is similar to the mortality rates reported in the literature for the treatment of mucormycosis.
Financial terms:
- Basilea will continue to be entitled to receive the same regulatory milestone and royalty payments in terms of value from Astellas relating to the U.S. and Canadian territories, with total milestone payments of up to CHF 374 million , including sales milestones.
Latest news:
- • On October 23, 2017, Basilea Pharmaceutica announced that the sales of the antifungal Cresemba® (isavuconazole) in the United States exceeded the threshold triggering the first sales milestone payment from Astellas Pharma to Basilea in the amount of CHF 5 million. Under the agreement with Astellas, Basilea is still eligible for additional sales milestone payments of up to CHF 285 million in addition to tiered, double-digit royalties on U.S. sales.
Is general: Yes
