Novartis Triumphs At EMA With Jetrea, But Merck Has Suspension of Three Merck Products Confirmed

The EMA has given the nod to Novartis subsidiary Alcon’s vitreomacular traction drug Jetrea and agreed to an indication extension for its Ilaris product to treat gouty arthritis. EMA’s Committee for Medicinal Products for Human Use also confirmed a recommendation to suspend the marketing authorizations of three Merck Sharp & Dohme products used to treat adults with dyslipidemia.

It was a good day for Novartis AG at the European Medicines Agency on Jan.18, with the Swiss company getting a positive opinion for an indication extension for llaris (canakinumab, ACZ885) to treat gouty arthritis. Novartis’ U.S.-based eye-care subsidiary Alcon Inc. also received a positive recommendation for its vitreomacular traction (VMT) drug Jetrea (ocriplasmin), a first-in-class product with a potential patient population of up to 300,000 in Europe.

A Breakthrough Product

It was actually the Belgian biopharmaceutical company ThromboGenics NV that filed the application for Jetrea at the EMA. However, Alcon gained exclusive ex-U.S. rights for the product, with an upfront payment of about $100 million in March 2012. Jetrea was approved in the U.S. in October 2012, for the treatment of patients with symptomatic vitreomacular adhesion (VMA), and ThromboGenics launched the product there earlier this month (Also see "ThromboGenics Takes Its Time On Solo Launch Of Eye Drug Jetrea" - Pink Sheet, 18 Oct, 2012.).

The Novartis-Alcon-ThromboGenics setup seems to be on to a winner with what the EMA’s Committee for Medicinal Products for Human Use (CHMP) has classed as a drug that serves an unmet medical need. Jetrea could have the VMT market sewn up, as the only other option currently on offer in Europe is observation until a patient becomes eligible for surgical intervention in the form of a vitrectomy – the removal of the vitreous from the eye – and repair of the retina. Still, the success of the drug ultimately will depend on intelligent pricing as it navigates its way through the European health technology assessment processes.

It’s not just the medicines agency and the manufacturers who believe the product is a breakthrough.

Albert Augustin, professor of ophthalmology and chairman of the Department of Ophthalmology at the Klinikum Karlsruhe in Germany, said, “Jetrea represents an important breakthrough for both physicians and patients and is expected to establish a new standard of care for patients with VMT and small macular holes.”

The EU regulatory submission was based on data from two pivotal Phase III clinical trials that evaluated the safety and efficacy of a single administration of Jetrea. Both studies met their primary endpoint and demonstrated that Jetrea successfully resolved VMT and macular hole compared to placebo. While reimbursement authorities would be looking to see Jetrea matched against a non-placebo comparator, the company is likely to have an easy ride given the drug’s unique position in the treatment pathway.

A Definitive Marketing Strategy

Novartis’s other triumph of the day was securing an indication extension for Ilaris. The drug was originally indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS) in adults, adolescents and children aged 2 years and older, now also will be used in patients with gouty arthritis.

More specifically, Ilaris is indicated for the symptomatic treatment of adult patients with frequent gouty arthritis attacks – at least 3 attacks in the previous 12 months – in whom non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate.

Studies show that Ilaris was more effective than placebo at treating patients with CAPS. None of the 15 patients who received Ilaris during the 24-week treatment period experienced a disease flare, compared with 81% of patients who received placebo (13 out of 16).

Ilaris has an interesting history at the EMA. It initially was approved under "exceptional circumstances" because Novartis was unable to provide comprehensive data on the efficacy and safety of the medicine, due to the rarity of the condition for which it was intended. Moreover, it was originally designated an orphan medicine on March 20, 2007, but this status was revoked at the request of the manufacturers. The latter move seems part of a Novartis strategy whereby it gets a foothold in the market for an initial indication and then seeks to expand this by providing data from additional studies at a later stage.

Novartis was the first Big Pharma to spearhead a rare diseases research initiative, but its approach is different from the rare disease efforts more recently adopted by its rivals. Building on the success of its leukemia drug Gleevec (imatinib), which launched in a rare disease and grew into one of the company’s best-selling drugs as it became licensed for additional types of cancer, Novartis is studying molecules first in small indications with well characterized, genetically defined patient populations, with the goal of eventually extending the research to broader disease areas (Also see "Novartis's Research Experiment" - In Vivo, 1 May, 2006.).

The drug’s progress in Europe is in stark contrast to its situation in the U.S. market. It received a complete response letter from FDA in August 2012, with the agency seeking more information, including clinical data to evaluate the biologic's benefit-risk profile in refractory patients (Also see "Novartis Takes Stock Of Ilaris For Gout Following FDA's Complete Response Letter" - Pink Sheet, 29 Aug, 2011.).

Another Jan. 18 winner at the CHMP included Pfizer Inc.’s chronic myelogenousleukemia (CML) treatment, Bosulif (bosutinib). Designated as an orphan medicinal product in August 2010, Bosulif has good hematological or cytogenetic response rates in patients with CML who were previously treated with one or more tyrosine kinase inhibitors and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.

But Bosulif’s marketing authorization will be conditional because the EMA panel decided that the data package was not comprehensive enough to satisfy its risk/benefit requirements. The authorization may be converted into a full marketing authorization at a later date, when more information becomes available. Pfizer will have to revisit the agency within a year to ensure that it has met the requirements for maintaining the conditional authorization.

Other products that received positive recommendations on extensions of therapeutic indications included Abbott Laboratories Inc.’s Humira (adalimumab), for polyarticular juvenile idiopathic arthritis; Bristol-Myers Squibb Co.’s Komboglyze (saxagliptin/metformin hydrochloride) for improving glycemic control in adult patients with type 2 diabetes mellitus; AstraZeneca PLC’s Onglyza (saxagliptin), also for improving glycemic control in adult patients with type 2 diabetes mellitus; and Roche’s Pegasys (peginterferon alfa-2a) in combination with ribavirin for the treatment of chronic hepatitis C in treatment-naïve children and adolescents 5 years of age and older, who are positive for serum HCV-RNA.

Trouble For Merck

As expected, the CHMP also confirmed a recommendation from the EMA’s Pharmaceutical Risk Assessment Committee to suspend the marketing authorizations of three Merck Sharp & Dohme Ltd. products used to treat adults with dyslipidemia (abnormally high blood levels of fats such as triglycerides and cholesterol), due to undesirable side effects.

A review of Tredaptive, Pelzont and Trevaclyn (nicotinic acid/laropiprant) began in December 2012, after new data from a large, long-term study called HPS2-THRIVE became available. Although the results are still preliminary, they suggest that taking nicotinic acid/laropiprant together with a statin has no significant additional benefit in reducing the risk of major vascular events such as heart attack and stroke, compared with statin therapy alone. In addition, a higher frequency of non-fatal but serious side effects was seen in patients taking these medicines.

The European Commission has also suspended the marketing authorization and supply of the medicines in the EU and Merck itself has announced that it is taking steps to suspend availability of the medicines across the region.