Products

Date: 2016-11-15

Type of information: Product launch

Product name: Cresemba®

Compound: isavuconazonium sulfate

Therapeutic area: Infectious diseases - Rare diseases

Action mechanism:

• systemic antifungal agent. Isavuconazole is an investigational 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.

Company: Basilea Pharmaceutica (Switzerland) Astellas Pharma (Japan)

Disease: mucormycosis

Latest news:

• • On November 2, 2017, Basilea Pharmaceutica announced that its licensing partner Pfizer recently launched Cresemba® (isavuconazole) in Spain. Pfizer is now commercializing the product in the major EU markets and Austria. In addition, Swissmedic approved Cresemba for the treatment of adult patients with invasive aspergillosis and for the treatment of adult patients with mucormycosis for whom amphotericin B is inappropriate.
• Cresemba® is currently being marketed in the U.S. by Basilea's licensing partner Astellas Pharma US; in Germany, Italy, the United Kingdom, France, Spain and Austria by Pfizer; and in the Nordic countries by Basilea's distribution partner Unimedic Pharma AB.
• • On November 15, 2016, Basilea Pharmaceutica announced that it has launched its antifungal Cresemba® (isavuconazole) in France and that it has sponsored a symposium on current challenges and recent opportunities in the treatment of invasive mold infections.• On June 27, 2016, Basilea Pharmaceutica announced that it has launched Cresemba®(isavuconazole) in Italy and has sponsored a continuing medical education event on current challenges and recent developments in the management of invasive fungal infections in Bologna, Italy. • On March 4, 2016,  Basilea Pharmaceutica Ltd. (SIX: BSLN) hosts a symposium to support the launch of Cresemba® (isavuconazole) in Germany. The focus of the symposium is on current challenges and recent developments in the management of invasive mold infections.
• • On March 3, 2016, Basilea Pharmaceutica hosted a symposium to support the launch of Cresemba® (isavuconazole) in the UK.
• • On October 16, 2015, Basilea Pharmaceutica announced that the European Commission has approved isavuconazole for the treatment of adult patients with invasive aspergillosis and for the treatment of adult patients with mucormycosis for whom amphotericin B is inappropriate.  The European Commission followed the positive opinion of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency recommending the approval of isavuconazole. The marketing authorization for isavuconazole will be valid in all 28 European Union (EU) member states, as well as in Iceland, Liechtenstein and Norway. With the approval of Cresemba® (isavuconazole) in Europe, Basilea expects to initiate a commercial launch of the drug in major European countries in early 2016.
• • On 23 July 2015, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Cresemba®, intended for the treatment of mucormycosis. Cresemba® will be available as 100 mg capsules and as a 200 mg powder for concentrate for solution for infusion. Cresemba®, through its antifungal action, has been shown to be effective at treating invasive aspergillosis and mucormycosis, which are life-threatening diseases with limited treatment options. The full indication is:"Cresemba® is indicated in adults for the treatment of invasive aspergillosis and for the treatment of mucormycosis in patients for whom amphotericin B is inappropriate. The positive CHMP opinion is based on results from the isavuconazole development program. The safety and efficacy profile of isavuconazole in patients with mucormycosis was demonstrated based on data from the VITAL study, which included a subpopulation of 37 patients with mucormycosis. All-cause mortality at Day 42 was 38% which is similar to mortality rates reported in literature for the treatment of mucormycosis. The efficacy of isavuconazole for the treatment of mucormycosis has not been evaluated in concurrent, controlled clinical trials.The most frequent adverse events for patients treated with isavuconazole in clinical phase 3 studies were nausea (26%), vomiting (25%), diarrhea (22%), headache (17%), elevated liver chemistry tests (17%), hypokalemia (14%), constipation (13%), dyspnea (12%), cough (12%), peripheral edema (11%), and back pain (10%).
• • On March 6, 2015, the FDA approved Cresemba® (isavuconazonium sulfate), a new antifungal drug product used to treat adults with invasive aspergillosis and invasive mucormycosis, rare but serious infections. Cresemba® is the sixth approved antibacterial or antifungal drug product designated as a Qualified Infectious Disease Product (QIDP). This designation is given to antibacterial or antifungal drug products that treat serious or life-threatening infections under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act. As part of its QIDP designation, Cresemba® was given priority review, which provides an expedited review of the drug’s application. The QIDP designation also qualifies Cresemba for an additional five years of marketing exclusivity to be added to certain exclusivity periods already provided by the Food, Drug, and Cosmetic Act. As these types of fungal infections are rare, the FDA also granted Cresemba® orphan drug designations for invasive aspergillosis and invasive mucormycosis.
• The approval of Cresemba® to treat invasive aspergillosis was based on a clinical trial involving 516 participants randomly assigned to receive either Cresemba or voriconazole, another drug approved to treat invasive aspergillosis. Cresemba’s approval to treat invasive mucormycosis was based on a single-arm clinical trial involving 37 participants treated with Cresemba and compared with the natural disease progression associated with untreated mucormycosis. Both studies showed Cresemba was safe and effective in treating these serious fungal infections. The most common side effects associated with Cresemba include nausea, vomiting, diarrhea, headache, abnormal liver blood tests, low potassium levels in the blood (hypokalemia), constipation, shortness of breath (dyspnea), coughing and tissue swelling (peripheral edema). Cresemba may also cause serious side effects including liver problems, infusion reactions and severe allergic and skin reactions.
• • On January 22, 2015, Basilea Pharmaceutica announced that the FDA Anti-Infective Drugs Advisory Committee voted eight to two with one abstention to recommend approval for the treatment of invasive mucormycosis (also known as zygomycosis), life-threatening fungal infections predominantly occurring in immunocompromised patients. Basilea's partner Astellas presented the data to the FDA and, if approved, intends to market the drug as Cresemba® in the United States. The Advisory Committee's recommendation is based on data from the isavuconazole development program, which included analyses from two phase 3 clinical trials in adult patients with invasive fungal infections: SECURE, a randomized, double-blind, active-control study of adult patients with invasive aspergillosis, and VITAL, an open-label non-comparative study of isavuconazole in adult patients with invasive aspergillosis and renal impairment or in patients with invasive fungal disease caused by other fungi, including those causing mucormycosis. Enrollment of patients into a third phase 3 study, ACTIVE, which assesses isavuconazole in the treatment of candidemia and other invasive Candida infections, was completed in January 2015 and topline data are anticipated for the second half of this year, following completion of treatment and follow-up periods.
• • On  September 6, 2014, Basilea Pharmaceutica announced that the FDA has accepted for filing the New Drug Application for isavuconazole submitted by Basilea's license partner Astellas Pharma Inc. The NDA seeks approval of isavuconazole for the treatment of invasive aspergillosis and invasive mucormycosis in adults. In accordance with the FDA Prescription Drug User Fee Act (PDUFA), the FDA designated the date of March 8, 2015 for the completion of the review. Based on the FDA's acceptance of filing of the U.S. NDA, Basilea will receive a CHF 12 million milestone payment from Astellas. The European regulatory review of Basilea's MAA could be completed by the fourth quarter of 2015.
• • On August 21, 2014, Basilea Pharmaceutica announced that the European Medicines Agency (EMA) has accepted its isavuconazole Marketing Authorization Application (MAA) for review. Basilea's MAA seeks approval of isavuconazole for the treatment of invasive aspergillosis and mucormycosis (zygomycosis) in adults. The EMA will review the application under the centralized marketing authorization procedure. If approved by the EMA, isavuconazole would receive marketing authorization in all 28 member states of the European Union (EU), as well as in Iceland, Liechtenstein and Norway.
• In July 2014, Basilea's co-development partner Astellas Pharma Inc. submitted a U.S. New Drug Application (NDA) seeking isavuconazole approval for the treatment of invasive aspergillosis and mucormycosis. Basilea is eligible to receive a milestone payment from Astellas upon the FDA's acceptance of Astellas' U.S. NDA submission. Basilea holds full rights to isavuconazole in markets outside of the U.S. and Canada where Astellas is the exclusive license holder.
• • On July 9, 2014, Astellas  announced it has submitted a New Drug Application (NDA) to the FDA seeking approval for isavuconazole for the treatment of invasive mucormycosis (also known as zygomycosis). In February, the FDA designated isavuconazole as a Qualified Infectious Disease Product (QIDP) for invasive mucormycosis. QIDP status provides priority review and a five-year extension of market exclusivity in the United States. Basilea will be eligible to a milestone payment upon FDA acceptance of the U.S. NDA submission.
• • On 8-9 April 2014, the Committee for Orphan Medicinal Products (COMP) has recommended the granting of an orphan designation for isavuconazonium sulfate for treatment of mucormycosis.
• • On February 27, 2014, Basilea Pharmaceutica has announced that the FDA designated isavuconazole as a Qualified Infectious Disease Product (QIDP) for the treatment of invasive mucormycosis (also known as zygomycosis). QIDP status provides priority review and a five-year extension of market exclusivity in the United States. In 2013, isavuconazole also received QIDP designation for the treatment of invasive aspergillosis, a severe fungal infection caused by widespread molds. These incentives were granted under the 2012 U.S. Generating Antibiotic Incentives Now (GAIN) Act as part of the FDA Safety and Innovation Act. In the event isavuconazole is approved in the United States, the five years QIDP market exclusivity would be in addition to the seven-year exclusivity based on isavuconazole\'s orphan drug designation for the treatment of zygomycosis that was granted by the FDA in 2013. In the U.S., isavuconazole also has FDA fast-track status and has received orphan drug designation for the treatment of invasive aspergillosis. Isavuconazole is currently in phase 3 clinical development. The results of the two recently completed phase 3 studies (SECURE and VITAL) are planned to form the basis of a potential regulatory filing for the U.S. and Europe mid-2014.
• • On November 18, 2013,  Basilea Pharmaceutica has reported that the FDA has granted orphan drug designation to isavuconazole for the treatment of zygomycosis (also known as mucormycosis), a life-threatening fungal infection. Due to their limited activity against Zygomycetes, voriconazole, fluconazole and the echinocandins are not indicated for the treatment of zygomycosis.
• Isavuconazole is currently in phase 3 of clinical development. Enrollment in the open-label phase 3 isavuconazole study (VITAL) including patients with invasive fungal disease caused by emerging fungal pathogens such as Zygomycetes and patients with aspergillosis and pre-existing renal impairment is complete (N=150). Based on the investigator reported data, approximately 45 patients were enrolled with mucormycosis (zygomycosis) and a similar number of patients were enrolled with pre-existing renal impairment. Review of diagnosis and outcomes by an Independent Data Review Committee is ongoing.
• Recently, positive topline results from the isavuconazole phase 3 invasive aspergillosis study (SECURE) were reported. Isavuconazole demonstrated non-inferiority versus voriconazole for the primary treatment of invasive fungal disease caused by Aspergillus species or certain other filamentous fungi. Isavuconazole was effective as determined by the primary endpoint of all-cause mortality through day 42 in the intent-to-treat population (N=516). Study drug-related adverse events were reported in 42.4% of the isavuconazole and 59.8% of the voriconazole treatment group. Overall drug- and non-drug-related adverse events were reported in 96.1% and 98.5% of patients in the isavuconazole and voriconazole treatment groups, respectively.

Patents:

Submission of marketing authorization application USA : 2014-07-09

Submission of marketing authorization application UE: 2014-07-17

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2015-03-06

UE authorization: 2015-10-15

Favourable opinion UE: 2015-07-23

Favourable opinion USA: 2015-01-22

Orphan status USA: 2013-10-25

Orphan status UE: 2014-06-04

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

• Astellas Pharma and Basilea Pharmaceutica have a License, Co-Development and Co-Promotion Agreement. This agreement has been amended in February 2014. Under the terms of the amended agreement, Astellas remains 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.

Is general: Yes