Arzerra gains NICE nod - but Imbruvica is waiting in the wings

GlaxoSmithKline has secured NICE approval for Arzerra, its chronic lymphocytic leukaemia (CLL) treatment – with a little help from a major discount.

The company has failed to make a success out of Arzerra since its launch in 2010, the drug earning just $70 million worldwide in the first nine months of this year, with Europe contributing just $28 million.

GSK has taken the decision to cut the drug's UK price as a wave of new, more effective treatments come onto the market.

Yesterday NICE gave preliminary approval to Arzerra (ofatumumab) in combination with chlorambucil as first line treatment for CLL, the most common form of leukaemia in England, for patients unable to take the standard fludarabine combination therapy (FCR) or bendamustine.

The NICE recommendation is the first for Arzerra (ofatumumab) since it was launched in 2010, having been rejected that year for patients with refractory disease.

The recommendation has been secured with the help of price reduction (which as usual, remains confidential) – but its low cost will now make it competitive with the existing first-line FCR combination, and offer fewer severe side-effects.

But in many ways, the move is too little, too late.

A triumvirate of new 'next generation' competitors is set to transform CLL treatment: Roche's Gazyva (obinutuzumab), Gilead's Zydelig (idelalisib) and Janssen and Pharmacyclics' Imbruvica (ibrutinib).

Gazyva and Zydelig have been launched in the UK in the last few months, and now Janssen's Imbruvica is poised to join the fray – and all look likely to provide superior efficacy compared to Arzerra.

Change ahead for Cancer Drugs Fund

However, market access for the new drugs won't be plain sailing. NICE has already issued preliminary guidance on Roche's Gazyva, rejecting its use in a first line setting (similar to Arzerra) because of 'data uncertainties'.

Roche's list price for a course of treatment of Gazyva is £26,496 – more than double the list price of Arzerra at £11,466, a cost cut further by the confidential discount.

Since 2011, companies with new cancer treatments either awaiting or refused NICE approval have been able to gain access to patients in England via the Cancer Drugs Fund (CDF).

The fund has been very helpful in providing an alternative route for cancer drugs, but the CDF is currently undergoing a major review, which looks likely to impose greater scrutiny on price and efficacy.

The consultation on how to reform the CDF (just concluded) means that no new treatments are currently being added to its approved list – including Gazyva, Zydelig and Imbruvica.

Despite these hold ups, analysts predict Janssen's Imbruvica and Gilead's Zydelig will emerge as the eventual leaders in CLL in global markets.

Zydelig is approved in Europe for use in combination with rituximab for adults with CLL who have received at least one prior therapy, or as first line treatment in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy.

Imbruvica is approved for use in CLL patients who have received at least one prior therapy, or first-line in those with the chromosomal abnormalities deletion 17p or TP53 mutation, as well as patients with the rarer Mantle Cell Lymphoma (MCL).

Janssen pitted Imbruvica against Arzerra in a phase 3 study, which saw Imbruvica win hands down: patients taking the drug saw a 78 per cent reduction in risk of disease progression or death compared to Arzerra.

Analysts forecasts this efficacy will propel Imbruvica to sales in excess of $3 billion by 2018, helped by combinations with other innovative cancer treatments.

Novartis to take on Arzerra

A further irony of GSK's belated NICE breakthrough with Arzerra is that the firm will soon hand it over to Novartis as part of a multi-billion dollar franchise swap. GSK is set to complete the exchange of its full oncology portfolio for Novartis' vaccines business in the first half of 2015. This should make the CLL field even more competitive: Novartis has achieved considerably more success in marketing oncology products than GSK, and is also working on a promising early-stage novel T-cell immunotherapy for CLL.