Amgen/UCB To Appeal EMA’s 'Over Cautious' Evenity Rejection
Executive Summary
Amgen and UCB say that the European Medicines Agency’s re-examination process should allow them to clarify their position on the data supporting the marketing authorization application for their osteoporosis drug, Evenity. Meanwhile, three other drugs received a positive opinion from the EMA this week for pan-EU approval, including La Jolla’s Giapreza.
Amgen and UCB will ask the European Medicines Agency to re-examine its decision to recommend against EU-wide marketing approval of their osteoporosis drug, Evenity (romosozumab). The drug is already authorized for use in the US and several other countries.
Serious cardiovascular safety concerns prompted the EMA's drug evaluation committee, the CHMP, to recommend against EU approval of the marketing authorization application (MAA) for Evenity. The product was up for an opinion at the CHMP's latest monthly meeting, which took place on 24-27 June. (Also see "Romosozumab Among Latest Drugs Up For CHMP Opinion" - Pink Sheet, 25 Jun, 2019.) The MAAs for the other three medicines – La Jolla Pharmaceutical’s Giapreza (angiotensin II), azacytidine from Celgene and lacosamide, also from UCB – all got the thumbs up.
Datamonitor Healthcare analyst Michael Haydock said it was "a bit harsh" of the CHMP to recommend against Evenity’s approval. "The drug could have been approved with a warning to exclude patients with previous CV events or other comorbidities that put them at high CV risk," as has been done in the US, Haydock told the Pink Sheet.
"I think the drug is clearly efficacious… but I think the EMA are probably being over cautious because it isn’t clear yet exactly which patient groups are at higher CV risk when receiving Evenity," Haydock added. The EMA said it was unclear why the medicine appeared to increase the risk of heart and circulatory problems, and there was no obvious group of patients in whom these risks were lower, due to which measures to reduce the risk could not readily be put in place.
No Joy For Novartis or PTC Therapeutics
There was also disappointment for Novartis and PTC Therapeutics, which failed to convince the CHMP to recommend extensions of the existing indications for their respective products, Revolade (eltrombopag) and Translarna (ataluren).
Novartis had wanted the indication for Revolade to be extended to include first line treatment of adult and pediatric patients aged two years and older with severe aplastic anaemia. PTC Therapeutics had applied for the indication of Translarna to be extended to include non-ambulatory patients with Duchenne muscular dystrophy. In both cases, the EMA opined that the risk:benefit balance in the requested indications could not be established and so recommended refusing the changes.
MAA Positive Opinions
The three MAAs that received a positive opinion from the CHMP were for:
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- La Jolla Pharmaceutical’s Giapreza (angiotensin II) for the treatment of refractory hypotension in adults with septic or other distributive shock. Giapreza was approved in the US in December 2017 following a priority review.
- Azacitidine Celgene, for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukemia and acute myeloid leukemia. Celgene submitted its marketing authorization application (MAA) for the product via an informed consent application. An informed consent application is one which makes use of data from the dossier of a previously authorized medicine, with the marketing authorization holder of that medicine giving consent for the use of their data in the application.
- Lacosamide UCB, for the treatment of partial-onset seizures with or without secondary generalisation. This was also submitted as an informed consent application by UCB.
New T2D Pediatric Indication For Victoza
The CHMP also recommended extensions of indication for 12 products, including for Novo Nordisk’s Victoza (liraglutide), in this case to include the treatment of children and adolescents aged ten years or older with type 2 diabetes.
The recommendation comes hot on the heels of the US approval earlier this month of Victoza for the treatment of type 2 diabetes in children aged 10 -17. (Also see "US FDA Approval Of Novo Nordisk's Victoza For Young T2D Patients A Treatment Milestone" - Scrip, 18 Jun, 2019.) Novo Nordisk said of the European development: “As the first GLP-1 receptor agonist approved for children and adolescents with type 2 diabetes, Victoza provides this population with a new treatment option, with the last new treatment approved back in 2000.”
The CHMP’s recommendations are forwarded to the European Commission for the final say; the commission usually takes 67 days to issue a legally binding decision.
Evenity Not Safe Enough For EU?
Although Evenity is approved in several markets, including the US, Japan and South Korea, the EU regulator continues to have concerns regarding the safety of the drug. Amgen and UCB had been scheduled to give an oral explanation regarding their MAA at the CHMP's meeting in May, indicating that the committee still had concerns at this late stage of the evaluation process. (Also see "Companies Keep The Faith As New Products Await EMA Verdict " - Pink Sheet, 28 May, 2019.)
At its latest meeting, the CHMP concluded that Evenity posed an increased risk of serious effects on the heart or circulatory system, such as heart attacks or strokes. Overall data showed that there were more deaths in patients aged over 75 years who were given the medicine.
The CHMP found that the drug was effective in reducing the risk of fracture in patients with severe osteoporosis, but it said that the benefit was "not so convincing in patients with less severe disease." It concluded that Evenity's benefits did not outweigh its risks as an osteoporosis treatment in women who have been through the menopause and men at increased risk of bone fractures.
Cardiovascular concerns regarding EVENITY are well known. In the US, for example, the product’s label contains a boxed warning stating that the drug may increase the risk of heart attack, stroke and cardiovascular death, and should not be used in patients who have had a heart attack or stroke in the previous year.
Haydock explained the black-box warning in the US means physicians are likely to only prescribe it to patients who they consider have low CV risk. Also, the US Food and Drug Administration has asked for a post-marketing CV study to explore further the drug’s CV safety, he added.
Haydock says the drug is "clearly efficacious" and causes relatively rapid increases in bone mass density - over 12 months compared to 24 months with Eli Lilly's Forteo (Teriparatide).
Amgen and UCB are planning to ask the CHMP to re-examine its negative opinion. They said the re-examination process would give them "the opportunity to clarify our position on the submitted data with the goal of making EVENITY available to postmenopausal women at high risk of fracture in the EU." The companies maintained the body of evidence it had submitted supported a positive benefit-risk profile for the drug.
While Amgen and UCB co-developed Evenity, Amgen filed for and received approval in the US and UCB filed for approval in the EU.
Amgen Withdraws Infliximab MAA
Also of note at the CHMP meeting, Amgen has withdrawn its MAA for infliximab (ABP 710), citing a change in strategy for the product.