DUBLIN – The FDA's surprise rejection of Amgen Inc.'s application for approval of Parsabiv (etelcalcetide) in secondary hyperparathyroidism (SHPT) is now looking even more curious, as the same drug is set to gain approval in Europe. During its September meeting last week, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended its approval in chronic kidney disease patients undergoing dialysis – and formal clearance will follow just over two months from now.

Amgen, of Thousand Oaks, Calif., has yet to disclose why the FDA refused its application for Parsabiv, a peptide-based calcimimetic, on Aug. 24. The CHMP's support for the drug deepens the mystery. Parsabiv is an agonist of the calcium-sensing receptor, a negative regulator of parathyroid hormone, which is elevated in SHPT. It reached the primary endpoint in two phase III placebo-controlled trials and a head-to-head trial against Sensipar (cinacalcet), long the standard of care in that indication. (See BioWorld Today, Aug. 26, 2016.)

At the same meeting, the CHMP also reversed its position on Takeda Pharmaceutical Co.'s application for approval of the oral proteasome inhibitor Ninlaro (ixazomib) in multiple myeloma. Barely more than three months after issuing a negative opinion on the drug, it is now backing its approval for treating relapsed myeloma in combination with Revlimid (lenalidomide, Celgene Corp.) and dexamethasone. The FDA had previously just taken four months to approve the same drug, which Takeda has positioned as a safer, oral successor to its venerable predecessor Velcade (bortezomib). (See BioWorld Today, Nov. 23, 2015.)

Phase III overall survival (OS) data are not yet mature, but Ninlaro combined with lenalidomide and dexamethasone showed a clear progression-free-survival (PFS) benefit vs. lenalidomide and dexamethasone only (20.6 months vs. 14.7 months). The CHMP originally ruled that it had failed to demonstrate sufficiently robustly that the drug worked in relapsed patients. Its reversal follows a Takeda-requested re-examination of the dossier – and consultations with experts who stressed its safety profile, its oral dosing and the future availability of survival data. The European approval is conditional, for now, pending the maturation of that survival data. (See BioWorld Today, June 1, 2016.)

Also recommended for European approval are Eli Lilly and Co.'s Lartruvo (olaratumab) in soft-tissue sarcoma, the type 2 diabetes combo Glyxambi (empagliflozin/linagliptin), developed jointly by Indianapolis-based Lilly and Ingelheim, Germany-based Boehringer Ingelheim GmbH, and Pfizer Inc.'s breast cancer drug Ibrance (palbociclib). New Brunswick, N.J.-based Johnson & Johnson's Janssen unit got a positive CHMP opinion to expand psoriasis drug Stelara (ustekinumab), an IL-12/23 inhibitor, for use in Crohn's disease patients who have had an inadequate response with, lost response to, or were intolerant to either conventional or TNF-alpha therapy.

Advanced Accelerator Applications SA, of Saint-Genis-Pouilly, France, also got a nod for Somakit TOC (edotreotide), a radiopharmaceutical for diagnostic imaging of gastroenteropancreatic neuroendocrine tumors.

Lilly's Lartruvo is still under regulatory review in the U.S. Even allowing for the propensities of the FDA and the EMA to diverge in their decision-making from time to time, a U.S. rebuff for Lartruvo would be a shock. The monoclonal antibody, which binds anti-platelet-derived growth factor receptor alpha, has both fast track and breakthrough therapy designation. In an open-label phase Ib/II trial in 133 patients, those on a combination of Lartruvo plus doxorubicin, the current standard of care, had an 11.8-month survival benefit over those on doxorubicin only (26.5 months vs. 14.7 months). The European approval is conditional, however, and it depends on the outcome of an ongoing phase III trial in 460 patients, dubbed Announce.

The only question mark hanging over Lartruvo is the discrepancy between its OS benefit and the more modest effects it had on PFS – a 2.5-month improvement – according to an analysis by Ian Judson and Winette van der Graaf, which Nature Reviews Clinical Oncology published online on Aug. 2. The sheer diversity of soft-tissue sarcoma could offer some clues, they noted. There are more than 70 histological subtypes, and imbalances in disease biology between the two study arms could have produced an anomalous result. The phase III data, when they appear, should help to clear up any ambiguity.

Janssen's Stelara in Crohn's disease also remains under regulatory review in the U.S.

The FDA approved diabetes drug Glyxambi in February 2015. The once-daily oral therapy is the first combination of an SGLT2 inhibitor and a DPP-4 inhibitor to gain approval. Around the same time, New York-based Pfizer gained FDA approval for Ibrance, its first-in-class inhibitor of cyclin-dependent kinases 4 and 6, for treating estrogen receptor-positive, HER2-negative metastatic breast cancer. The product is already Pfizer's best-selling oncology drug, with second-quarter sales of $514 million. The European approval will help to put a little more daylight between it and a fast follower molecule, ribociclib, which Basel, Switzerland-based Novartis AG is developing.

North Chicago-based Abbvie Inc. withdrew an application for Cokiera, a quad hepatitis C therapy comprising dasabuvir, ombitasvir, paritaprevir and ritonavir, once it became evident that the CHMP was unlikely to support its approval on the basis of the data Abbvie provided. The same regimen is marketed in the U.S. as Viekira XR. An Abbvie spokeswoman downplayed the significance of the refusal. "We do not anticipate any material impact as a result of this decision," she stated.