Optimer's Fidaxomicin Among Three NMEs Given Positive Review By Europe's Regulators

EU's scientific advisory panel also recommends approval for Takeda's azilsartan and Tibotec's rilpivirine, and grants positive opinions on new indications for Bayer/Johnson & Johnson's rivaroxaban and Alexion's eculizumab.

Optimer Pharmaceuticals Inc.'s anti-clostridial antibiotic, fidaxomicin (Dificlir), was among three new molecular entities granted positive opinions by the EU's scientific advisory panel, the Committee for Medicinal Products for Human Use (CHMP), on Sept. 23.

CHMP that day also gave its okay to Takeda Pharmaceutical Company Ltd.'s angiotensin II receptor inhibitor, azilsartan medoxomil (Edarbi) for hypertension, and Tibotec Pharmaceuticals Inc.'s HIV therapy, rilpivirine (Edurant).

In addition, the Committee issued positive opinions on major new indications for Bayer AG/Johnson & Johnson's oral anticoagulant, Xarelto (rivaroxaban) and Alexion Pharmaceuticals Inc.'s Soliris (eculizumab), and gave a green light to AstraZeneca plc/Bristol-Myers Squibb & Co's new combination antidiabetic, Komboglyze and Novartis AG's triple combination antihypertensive, Rasitrio. Final approvals will be granted by the European Commission over the next several months.

Fidaxomicin Welcomed By EMA

The European Medicines Agency took the unusual step of welcoming CHMP's positive opinion on fidaxomicin, which will be marketed in Europe by Astellas Pharma Europe Ltd under a $200 million licensing deal signed with Optimer in February (Also see "Emboldened By Strong Data, Optimer Licenses Antibiotic Candidate To Astellas" - Pink Sheet, 7 Feb, 2011.)).

"Infection with Clostridium difficile is one of the leading causes of disease in hospitals," the EMA pointed out. The bacterium causes inflammation of the gut and severe diarrhea, particularly in patients treated with other antibiotics, and the number of cases is on the increase following the emergence of a new, more virulent strain that has spread to 17 European countries, the agency said. The infection costs the EU economy more than €3 billion ($4 billion) annually, and EMA's targets include reducing the deleterious impact of infectious diseases on the region.

Fidaxomicin was approved for marketing in the U.S in May as Dificid, and has been recommended for a similar indication in Europe as that granted in the U.S. -treatment of adults with C difficile infection, also known as C difficile-associated diarrhea (" (Also see "Optimer Looking At Prophylaxis As Next Frontier For C. Difficile Agent Dificid" - Pink Sheet, 6 Jun, 2011.)). Fidaxomicin is a macrocyclic antibiotic which inhibits bacterial RNA polymerase at a site distinct from that of the rifamycins, a class of antibiotics with a similar mode of action. Astellas also has marketing rights to the product for certain countries in the Middle East, Africa and the Commonwealth of Independent States.

Azilsartan Joins Crowded Market

Azilsartan medoxomil was recommended for the treatment of essential hypertension in adults, but will join a crowded marketplace for antihypertensive therapies when it is finally approved. The EU positive opinion comes six months after the product was approved for the same indication in the U.S. (Also see "Takeda's Edarbi Joins Busy Hypertension Field With Comparative Data" - Pink Sheet, 7 Mar, 2011.)).

Azilsartan, an angiotensin II receptor antagonist, will have to contend with products with the same mode of action being available as generics, such as Merck & Co.'s losartan (Cozaar). Generics of the leading angiotensin II receptor antagonist, Novartis' Diovan (valsartan) already are available in Spain, and are expected shortly in other European countries (Also see "Novartis Boosted By Alcon, Generic Sales And Gilenya Launch in Second Quarter" - Pink Sheet, 19 Jul, 2011.)).

Rilpivirine: Alone Or In Gilead's Combination

Rilpivirine is a non-nucleoside reverse transcriptase inhibitor developed by Tibotec with another Johnson & Johnson affiliate, Janssen-Cilag International NV, and was recommended by CHMP for the treatment of HIV-1 infection either alone, as Edurant 25mg tablets, or in combination with two other HIV therapies, emtricitabine and tenofovir disoproxil, as Gilead Sciences Inc.'s Eviplera.

Gilead entered into a collaboration with Tibotec in June 2009 to develop and market the triple combination in the U.S., Europe and other markets. It was approved in August in the U.S. as Complera (Also see "Gilead Complera Launch Imminent Following FDA Approval" - Pink Sheet, 11 Aug, 2011.)).

The recommendation is the second piece of good news from Europe for Tibotec/Janssen in the past few days. On Sept. 20, the European Commission approved its protease inhibitor, Incivo (telaprevir), for the treatment of hepatitis C in combination with peginterferon alfa and ribavirin, following a positive opinion issued by CHMP in July (Also see "Positive Opinions in Europe For J&J's Zytiga And Telaprevir, Pfizer's Tafamidis And Orion's Dexmedetomidine" - Pink Sheet, 22 Jul, 2011.)). Teleprevir was developed in collaboration with Vertex Pharmaceuticals Inc. and Mitsubishi Tanabe Pharma, with Janssen/Tibotec holding marketing rights in Europe and certain other countries.

New Strengths For Xarelto

Additional indications cleared by CHMP for products already marketed in Europe include Xarelto being recommended for the prevention of atrial fibrillation-related stroke, and the treatment of deep vein thrombosis (DVT) and the prevention of recurrent DVT and pulmonary embolism (PE) following an acute DVT.

The two new indications were recommended for two new strengths of Xarelto, 15 mg and 20 mg tablets, while the current indication, prevention of venous thromboembolism in adult patients undergoing hip and knee replacement, was maintained for the marketed 10 mg tablet. Being able to administer 20 mg of rivaroxaban once daily may be a key advantage for Xarelto over other new oral anticoagulants, although other regulators, such as FDA, are thought to favor twice-daily dosing for its efficacy and safety advantages (Also see "ROCKET AF’s Design Causes Headaches For Xarelto Sponsors" - Pink Sheet, 19 Sep, 2011.)).

CHMP gave a green light to Solaris' indications being extended to include the treatment of pediatric and adult patients with atypical hemolytic uremic syndrome. Soliris already is marketed in Europe for the treatment of paroxysmal nocturnal hemoglobinuria. A supplemental BLA for the same indication has been submitted to the U.S.FDA.

AstraZeneca's Komboglyze Okayed

AstraZeneca and Bristol-Myers Squibb received a boost from CHMP with its positive opinion on their antidiabetic combination tablet, Komboglyze (saxagliptin and metformin). Approval of the combination is expected to allow the companies to compete more effectively with the market leader, Merck & Co.'s Januvia (sitagliptin).

Novartis gained a positive recommendation from the committee for another of its single-pill combination antihypertensive therapies, this time a triple combination of the rennin inhibitor, aliskiren, the calcium channel blocker, amlodipine and the diuretic hydrochlorothiazide, which will be marketed as Rasitrio. The triple combination was approved in the U.S. in December 2010 as Amturnide.

The Swiss company already markets a dual combination of aliskiren and HCTZ in Europe as Razilez HCT, and an aliskiren plus amlodipine combination as Rasilamlo. However, it removed Rasilamlo from the German market earlier this month because it disputed new requirements for the pricing and reimbursement of new drugs (Also see "German Reimbursement Assessment Process Fells Third Rx Victim" - Pink Sheet, 6 Sep, 2011.)).

- John Davis ([email protected])