DUBLIN – The EMA closed the doors on its London office for the last time on Friday, bringing to an end a 24-year history during which drug regulation in Europe evolved from a set of stand-alone, national competencies to a seamless shared endeavor across the European Union's member states. Long one of the EU's largely invisible successes, its very lack of public profile was testament to the quiet efficiency with which it went about its business. Although the whole Brexit process is still mired in myriad uncertainties, the EMA is preparing for a new chapter in which the U.K.'s influential Medicines and Healthcare Products Regulatory Agency (MHRA) will no longer play an active role in pan-European drug regulation, once the U.K. exits the European Union. Although that is supposed to happen on March 29, whether it will is still an open question.

Amid all the history, it was also business as usual at the EMA last week, as the agency's Committee on Human Medicinal Products (CHMP) disclosed Friday the key regulatory decisions taken during its February meeting. Chief among those was a decision to diverge from the FDA in recommending the antisense drug Waylivra (volanesorsen) for conditional approval as a treatment for patients with familial chylomicronemia syndrome (FCS) who have a high risk of developing pancreatitis. It's a boost for its developers, Boston-based Akcea Therapeutics Inc. and its parent firm Carlsbad, Calif..-based Ionis Pharmaceuticals Inc., as they seek a path forward in the U.S. after receiving a complete response letter for the same drug last year. (See BioWorld, Aug. 29, 2018).

The rare genetic condition, which arises from a lack of lipoprotein lipase (LPL) activity, leads to the accumulation of triglycerides in the blood. Those are carried in large lipid particles called chylomicrons, which can block blood flow in the pancreas and cause acute pancreatitis attacks. Volanesorsen is designed to counteract that process by inhibiting production of Apolipoprotein (ApoC-III), which controls plasma triglyceride levels by inhibiting LPL and by inhibiting additional pathways that are independent of LPL.

Although the CHMP noted that the use of the drug can lead to reduced blood platelet counts, as well as injection site reactions, it decided that the benefits of sharply reducing fasting triglyceride levels – by 77 percent from baseline in the phase III Approach study – outweigh the accompanying risks. Although the FDA's Endocrinologic and Metabolic Drugs Advisory Committee had voted narrowly in volanesorsen's favor, it did question the clinical relevance of triglyceride reduction as an endpoint, given the lack of evidence for the drug's effects on abdominal pain and reducing pancreatitis attacks. (See BioWorld, May 9, 2018, and May 11, 2018.)

Another big winner was Lexicon Pharmaceuticals Inc., of The Woodlands, Texas, whose stock (NASDAQ:LXRX) rose as much as 31 percent – closing Friday at $6.81 – on news that the CHMP backed approval of Zynquista (sotagliflozin), a dual inhibitor of sodium glucose co-transporter (SGLT) 1 and SGLT2, as an add-on to insulin for patients with type 1 diabetes. The drug showed positive effects on glycemic control, weight loss and lowering of blood pressure, while also decreasing the variability of patients' blood sugar levels.

The drug, which Lexicon co-developed with Paris-based Sanofi SA, received a tied vote from the FDA's Endocrinologic and Metabolic Drugs Advisory Committee in January. Like other SGLT inhibitors, sotagliflozin increases the risk of diabetic ketoacidosis, a potentially fatal complication arising from the breakdown of fat into ketones. The CHMP has accordingly recommended that use of the drug be limited to patients who are overweight or obese, with a body mass index of 27 kg/m2 or higher. The FDA's regulatory decision is expected by March 22.

Portola Pharmaceuticals, Inc., of South San Francisco, also enjoyed a stock market bounce, on a positive CHMP vote for Ondexxya (andexanet alfa), its antidote to two anticoagulants, rivaroxaban (Xarelto, Janssen Pharmaceuticals Inc.) and apixaban (Eliquis, Pfizer Inc./Bristol-Myers Squibb Co.) for patients in receipt of either therapy who experience uncontrolled or life-threatening bleeding. The stock (NASDAQ:PTLA) closed Friday at $34.72, up $4.01.

The CHMP also voted in favor of North Chicago-based Abbvie Inc.'s interleukin-23 (IL-23) inhibitor Skyrizi (risankizumab) as a psoriasis treatment. The drug, a potential blockbuster according to some analysts, is still undergoing FDA review, with an estimated PDUFA date of April 24. San Rafael, Calif.-based Biomarin Pharmaceutical Inc., was another winner, with a positive vote for Palynziq (pegvaliase), its enzyme substitution therapy for adult patients with phenylketonuria (PKU), which gained FDA approval last year. The treatment is not a direct replacement for phenylalanine hydroxylase, which is absent from PKU patients – it comprises a pegylated form of another enzyme, phenylalanine ammonia lyase, which also breaks down phenylalanine, the accumulation of which, if untreated, causes intellectual disability. (See BioWorld, May 29, 2019.)

New York-based Pfizer Inc. followed up its FDA approval last November for lorlatinib in anaplastic lymphoma kinase (ALK)-positive metastatic non-small-cell lung cancer (NSCLC) with a nod for the same indication in Europe, on a conditional basis initially. The drug is marketed as Lorbrena in the U.S., but will be branded as Lorviqua in Europe. (See BioWorld, Nov. 6, 2018.)

London-based Glaxosmithkline plc secured backing for Dectova (zanamivir), a new formulation for infusion of its neuraminidase inhibitor, for treating complicated and potentially fatal influenza infections in adult and pediatric patients whose infections are resistant to other antivirals or for whom other drugs, including inhaled zanamivir (marketed as Relenza), are not considered appropriate.

The EMA will start to move into temporary accommodations in its new home city of Amsterdam from March 11. Its permanent home is due to be completed in November. Its personnel will work remotely next week.