Who has the richest pipeline of them all? Some of the findings from an analysis of the sales potential of late-stage assets are fairly predictable – GlaxoSmithKline languishes at the bottom of the chart, with its phase II and III projects predicted to bring in just $2.1bn over the next five years. But others are more surprising (see table below).
One startling fact is that Merck & Co tops the forecast, mainly due to its hepatitis C combination pill grazoprevir/elbasvir, set to be a blockbuster drug in its first full year of sales and bring in $3.1bn by 2020. Roche sits in second place, with its biggest contributors the anti-PD-L1 MAb atezolizumab and the dry age-related macular degeneration candidate lampalizumab.
|Forecast sales for phase II + III projects ($bn)|
|Merck & Co||<0.1||0.8||2.0||3.4||4.5||5.4||16.1|
|Johnson & Johnson||-||0.1||0.3||0.7||1.1||1.5||3.7|
Another arguably counterintuitive finding is that those companies with the most late-stage assets are not those set to see the biggest returns – in fact the opposite seems to be true, with Glaxo second in the late-stage project count. This may call to mind the adage concerning quality over quantity.
Hep C combo
Merck filed grazoprevir/elbasvir with the FDA in May and it is already being touted as a rival to Gilead’s Harvoni, helped by promising results from the phase III C-Edge trial. Grazoprevir/elbasvir has the advantage that it can also be used in patients with genotypes 1, 4 and 6, while Harvoni is only effective on genotype 1.
Hep C has of course been a lucrative sector, but drug developers are already facing pressure from payers who baulk at the $1,000-a-day price tag of the likes of Harvoni and Solvadi. If this pressure leads to big discounts it could impact Merck’s future sales. And the company will also have to contend with incoming triple combinations including Gilead’s GS-9857/SOF/GS-5816, which could reach the market in 2018.
Some of Merck’s other potential big earners are on shakier ground. A phase III study of its cholesterol-targeting CETP inhibitor anacetrapib is due to report interim results any time now, and the company will be hoping it does not go the way of Pfizer’s torcetrapib or Roche’s dalcetrapib.
Another high-risk project is the Alzheimer’s candidate MK-8931, which aims to prevent beta-amyloid build-up by inhibiting the beta-secretase cleaving enzyme. Developing disease-modifying drugs based on the amyloid hypothesis has been notoriously difficult – just ask Lilly or Biogen (Glimmers of support, but no Alzheimer’s breakthrough, July 23, 2015).
If both anacetrapib and MK-8931 fail, $1.4bn would be wiped off Merck’s total cumulative forecast sales, according to EvaluatePharma's consensus estimates – a sizeable chunk, although not as big as grazoprevir/elbasvir’s contribution.
Roche immuno-oncology promise
This could work in Roche’s favour. Its most promising prospect, atezolizumab, will soon be filed in its first potential indications, metastatic non-small cell lung cancer and metastatic urothelial bladder cancer – but it is also being trialled in other cancers including breast and colorectal. Roche recently teamed up with Immune Design to investigate atezolizumab in combination with the latter's CMB305 in phase II in soft tissue sarcoma.
AstraZeneca talked up its pipeline when Pfizer came calling, and the analysis suggests that this stance was justified, putting it in third place. Its top late-stage assets are both in phase III in non-small cell cancer the anti-PD-L1 immuno-therapy MEDI4736 and the EGFR-targeting AZD9291.
But these will need to live up to expectations: the UK company will become ever-more reliant on its pipeline as key patent expiries take hold.
At rock bottom in the forecast, Glaxo might be regretting its asset swap with Novartis. And without its asthma antibody Nucala its future would look even grimmer: sales of the product are anticipated to hit a rich-looking $1.1bn by 2020, over half of the company’s cumulative total.
Even Novartis, the world’s biggest drug company by sales, has a far from impressive pipeline, with none of its late-stage assets forecast to bring in $1bn or more by 2020. But it does have two of the biggest approvals of the year already in the bag in the shape of the heart failure pill Entresto and the interleukin-blocking antibody Cosentyx (2015 NME outlook sustains bullish outlook, July 20, 2015).
A look at second-bottom Bristol-Myers Squibb tells a similar story – the company is relying on its immuno-oncology product Opdivo but with 2020 revenues of $7.5bn predicted, this is not a bad position to be in.