DUBLIN – Shares in Xbiotech Inc. (NASDAQ:XBIT) fell by 41 percent Friday on news that its European application for its advanced colorectal cancer therapy Xilonix (MABp1), was likely to fail. The stock opened at $10.39 Friday, down $6.63 from its previous close and never regained ground, ending the day at $10.23, down 40 percent.

The EMA's Committee on Human Medicinal Products (CHMP) did not issue a formal refusal to the Austin, Texas-based biotech, but the company learned it was on track to receive one during an oral hearing Thursday. Xilonix, an antibody that targets interleukin-1-alpha (IL-1 alpha), had been in development as a symptomatic therapy. The drug was being assessed for its ability to stabilize or increase body mass in patients with cachexia and to improve pain, fatigue and anorexia, but the CHMP questioned the clinical relevance of the supporting data and raised additional quality assurance problems to boot.

The company had trumpeted the regulatory pathway it was pursuing, which it said "was devised around an EMA mandate" to find new ways of assessing therapies for patients with advanced cancers. Its phase III trial was compromised, however, by several deviations from the study protocol, which meant it had to discard data from 72 of the 333 patients enrolled and lose a lot of its statistical power. Even so, it reported that Xilonix reached the primary endpoint of the study immediately prior to submitting its application – 33 percent of patients demonstrated a clinical response vs. 19 percent of those on placebo, a relative improvement in response rate of 76 percent. (See BioWorld Today, Dec. 8, 2015.)

The data also appeared in the February 2017 issue of The Lancet Oncology, in a paper, "MABp1 as a novel antibody treatment for advanced colorectal cancer: a randomized, double-blind, placebo-controlled, phase 3 study." Xbiotech officials were not available for comment Friday, but CEO and President John Simard stated in a news release that the company "may seek access" to the EMA appeals process "at the appropriate time."

Xbiotech was the biggest casualty of the CHMP's monthly meeting, but it did not actually feature in the agency's formal dispatches. The committee recommended 11 drugs for approval, including two new medicines, four orphan drugs, three biosimilars and two drugs submitted under the generic or hybrid regulatory pathway. Notable approvals included Biogen Inc.'s Spinraza (nusinersen), which already has FDA approval, for treating spinal muscle atrophy, and Biomarin Pharmaceutical Inc.'s Brineura (cerliponase alfa) for treating neuronal ceroid lipofuscinosis type 2, a pediatric brain disorder. The latter decision will buoy Biomarin ahead of the April 27 FDA PDUFA date for the same drug. (See BioWorld Today, Dec. 28, 2016.)

Pfizer Inc. also received a boost, with a positive decision for its antibody-drug conjugate, Besponsa (inotuzumab ozogamicin), in CD22-positive acute lymphoblastic leukemia. That follows a failed phase III program in non-Hodgkin lymphoma. (See BioWorld Today, May 22, 2013.)

Regeneron Pharmaceuticals Inc. and Sanofi SA followed up their recent Health Canada approval of interleukin-6 receptor inhibitor Kevzara (sarilumab) in rheumatoid arthritis with a positive European recommendation. The drug is still stuck at the FDA, following an initial rebuff because of GMP problems. (See BioWorld Today, Oct. 31, 2016.)

DEBATE OVER NEW EMA HOME

How many more CHMP meetings will be held in London is an open question for now – but maybe for not much longer. Some of the heavy hitters of the European and global pharmaceutical industry have added their voice to the debate on a new home for the EMA in the wake of the U.K.'s decision to leave the European Union. In an open letter published by the European Federation of Pharmaceutical Industry Associations (EFPIA), 19 big pharma and biotech R&D heads called on the European Council – the heads of the European Union's member states – to make a quick decision on the EMA's new location, in order to safeguard its continued smooth operation.

The group stated that the decision should be made on the basis of "very essential criteria" and that it should preferably be finalized at the council meeting to be held on June 22-23. Whether that timetable is feasible should become clearer this week, as the council is meeting in Brussels Saturday to adopt guidelines for the upcoming Brexit negotiations.

Those making the call include: Paul Stoffels, of Johnson & Johnson; Patrick Vallance, of Glaxosmithkline plc; Jay Bradner of Novartis AG; Menelas Pangalos, of Astrazeneca plc; Elias Zerhouni, of Sanofi SA; John Reed, of Roche Holding AG; Mads Krogsgaard Thomsen, of Novo Nordisk A/S; Luciano Rossetti, of Merck KGaA; Roger Perlmutter, of Merck & Co. Inc.; Mikael Dolsten, of Pfizer Inc.; Jan Lundberg, of Eli Lilly and Co.; Sean Harper, of Amgen Inc.; Andreas Busch, of Bayer Pharmaceuticals AG; Ismail Kola, UCB SA; Michel Pairet, of Boehringer Ingelheim GmbH; Alexandre LeBeaut, of Ipsen SA; Emmanuel Canet, of Les Laboratoires Servier; Michael Hayden, of Teva Pharmaceutical Industries Ltd.; and Andrew Plump, of Takeda Pharmaceutical Co. Ltd.

Their letter contains a blunt warning to politicians on the necessity of getting the decision right. "For over two decades, EU member states have benefited from and relied upon the critical work undertaken by the EMA in relation to the approval of new medicines, pharmacovigilance and safety monitoring activities," they stated. "It is a stark and alarming reality that such fundamental activities would undoubtedly be impeded were the operations of the agency to be disrupted as a result of the United Kingdom's exit from the EU. To put it concisely: in the event of obstruction or failure, Europe possesses no backup option."

Morale among EMA staffers is reportedly low. The collective mood can't be helped much by the spectacle of politicians lining up across most of the EU's remaining 27 member states to claim the agency as some sort of a prize, based more on domestic political considerations and intergovernmental horse-trading than on any real engagement with the intricate workings of the EMA. While the agency has a core staff of about 900 people, it relies on the expert input of 4,000 more drawn from national regulators.

Key criteria for its new home include excellent transport connections and the year-round availability of about 400 hotel rooms every night, as well as access to good housing and schools for its permanent staff and their families. Quite a few of the cities putting themselves forward as candidates to host the agency would fail to meet those very basic criteria.

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