LONDON – Novartis U.K. Ltd. and Bayer plc have lost a legal action they launched in the U.K. to prevent the cancer drug Avastin (bevacizumab) from being used in preference to their more expensive products in the treatment of wet age-related macular degeneration (AMD).

The judge ruled clinicians can lawfully choose Avastin on the grounds of cost, even though it is not licensed for ophthalmic use.

The "extraordinary judgment" potentially undermines the regulation of all medicines, said the Association of the British Pharmaceutical Industries (ABPI) in response to the ruling, while Bayer called it "a setback for public health."

Novartis said the ruling jeopardizes a "well-established legal and regulatory framework that is there to protect both patients' safety, and to ensure health care professionals can prescribe with confidence."

But the defendants in the case, 12 clinical commissioning groups (CCGs) in the north of England, said Avastin is "undeniably, equally effective and much less expensive" than the two licensed AMD anti-VEGF treatments, Bayer's Eylea (aflibercept) and Novartis' Lucentis (ranibizumab).

"It's a victory for common sense over commercial interests," said David Hambleton, chief officer of South Tyneside CCG, speaking on behalf of the 12 CCGs.

Unlike in other markets, there has been limited use to date of Avastin in AMD, and analysts said there could be a significant impact on U.K. sales of Eylea and Lucentis.

The two pharmas took the 12 CCGs to court to prevent them from implementing a joint policy of offering Avastin as the preferred treatment for wet AMD. The companies claimed the policy was unlawful because the EMA has not licensed the cancer drug in ophthalmic indications and its use undermined patients' rights of access to treatment with Eylea and Lucentis.

The high court ruling will usher in a decisive shift in the U.K., where the official government position has been that it is illegal and against the wider public interest to use Avastin to treat AMD.

That position was set out in March 2015, in response to a call for clarity from CCGs following five years' of inconclusive consultations on the issue.

The government's attempt to hold the line was undermined last year when the health technology assessment body, the National Institute of Health and Care Excellence (NICE), issued a provisional guideline on AMD – subsequently made definitive in January – which stated the three anti-VEGF agents have equivalent safety and clinical effectiveness.

That led the 12 CCGs to adopt their policy of preferring Avastin on the grounds that it is more cost-effective than Lucentis and Eylea, prompting Bayer and Novartis to ask for a judicial review in November 2017.

The high court judgment quotes list prices of £28 (US$36.75) per injection for Avastin, £816 for Eylea and £551 for Lucentis. In fact, it is impossible to make a precise evaluation of how much can be cut from the drugs bill by using Avastin rather than Eylea or Lucentis because Bayer and Novartis have agreed to confidential discounts with the U.K. Department of Health, and CCGs also may negotiate discounts.

However, there are undoubtedly savings to be made. The 12 CCGs that were taken to court by Bayer and Novartis said they will save in excess of £13.5 million per annum. Translated to the U.K. as whole, that could amount to £500 million.

The ruling is a vindication for the Royal College of Ophthalmologists, which has been campaigning since 2012 for Avastin to be used for wet AMD, said Andrew Lotery, the college's scientific chair. "Our members can now feel assured they can offer the best treatment for their patient's individual needs," he said.

Avastin 'will penetrate' AMD space

A study carried out in 2015 found Lucentis accounted for 61 percent of treatments in the U.K., Eylea 36 percent and Avastin 3 percent.

The high court ruling could make a big dent in U.K. sales of Eylea and Lucentis, according to Edit Kovalcsik, pharma analyst at the market research firm Globaldata. The fact that the government has held out against unlicensed use of Avastin means the U.K. is the second largest market for the two approved anti-VEGF AMD treatments after the U.S., accounting for 18 percent of global sales.

That is about to change. As a result of the NICE guidance and the court ruling, Avastin "will penetrate the U.K. wet AMD space," Kovalcsik said.

Sheuli Porkess, deputy chief scientific officer of ABPI, reacted strongly against the ruling. It "potentially undermines the regulation of all medicines," she said. As a result, "neither patients nor doctors have clarity in what information to trust." The confusion is all the more worrying, given the U.K.'s hopes for regulatory cooperation with the EMA after Brexit.

Both Novartis and Bayer issued hard-hitting statements saying they are considering appealing the decision.

"The ruling threatens to jeopardize a world-leading system that has protected patients for many years by ensuring medicines have been tested rigorously and carefully scrutinized for delivering value," Novartis said.

Bayer said using Avastin for AMD "risks increasing the number of clinic visits and injections a patient needs for proper monitoring." That would place "more of a strain on [the] National Health Service and the already-stretched workload of NHS staff."

Advocates of using Avastin in AMD point out its lack of a license is not because the EMA has found against it, but rather that its owner, Roche Holding AG, has not applied for marketing approval in the indication.

However, there is plenty of real-world evidence from unlicensed use and from trials sponsored, among others, by the NIH and NICE, indicating Avastin has equivalent efficacy and safety. (See BioWorld Today, May 9, 2012.)

"Novartis and Bayer have argued long and hard for the more expensive drugs they'd rather sell to be the only ones available to people [with AMD], but thankfully the court has recognized there is no medical basis for that argument," Hambleton said.