It has been said that 2016 was a comparatively slow year on the R&D news front – an opinion that is confirmed by a look at how the sell-side’s view of the industry’s pipeline has shifted. No development stage product received “blockbuster” upgrades to their outlook last year, EvaluatePharma data reveal, in stark comparison to previous years.
The biggest upgrade of the year was Dupixent, the Sanofi/Regeneron antibody that should reach the market later this year. There were notable downgrades, however, with the collapse of Fovista weighing heavy and worsening prospects for Puma’s neratinib; both of these drugs saw more than $1bn wiped from their 2020 sales forecasts.
The analysis was constructed using archived sell-side consensus sales forecasts for 2020, ranked to show the biggest movements; yesterday included a look at marketed products (Darzalex and Keytruda win 2016’s sell-side popularity contest, February 8, 2017). Today this was restricted to products that remain in development.
When EP Vantage has run these numbers the last few years, the output has held at least three products that have received billion-dollar upgrades to their outlooks (Roche gets back to business – R&D upgrades and downgrades, February 10, 2016).
Interestingly, Merck’s Alzheimer’s candidate verubecestat has seen substantial upgrades since May – well before the solanezumab failure in December, which dealt a blow to the anti-amyloid hypothesis. Verubecestat, a BACE inhibitor, is also designed to reduce beta-amyloid levels but via a different mechanism to beta-amyloid antibodies like sola.
And in spite of the sola setback, there are still people who believe in the amyloid hypothesis in the absence of another unifying theory of Alzheimer’s. Verubecestat will soon be put to the test, with data from the pivotal Epoch study due mid-year.
|Five biggest upgrades to R&D assets over the past 12 months|
|Product||Company||Therapeutic Subcategory||2020e sales ($m)||Change ($m)|
|Verubecestat||Merck & Co||BACE inhibitor; Alzheimer's||782||744|
|Tremelimumab||Astrazeneca||Anti-CTLA-4 cancer antibody||986||691|
|Apalutamide||Johnson & Johnson||Anti-androgen; prostate cancer||822||672|
|Emicizumab||Roche||Haemophilia bispecific antibody||786||646|
Another highly anticipated read out involves Astra’s tremelimumab, which is being tested in combination with its PD-L1 inhibitor durvalumab in the Mystic trial in first-line lung cancer. Forecasts for treme soared in August, but this was before recent amendments to Mystic that might hint at fading confidence in the product (Astra’s Mystic mystery and other surprises in store, January 17, 2017).
Anything less than efficacy in patients who do not express high levels of PD-L1 could put treme on the wrong side of this analysis next time.
Meanwhile, Johnson & Johnson’s Zytiga follow-on apalutamide is expected to offset declining sales of the older drug, should it succeed in the Spartan trial and get approved. The entrance of apalutamide is expected to hit Astellas’s Xtandi, which was among the marketed products with the biggest downgrades yesterday.
An old fashioned clinical setback was responsible for Fovista's massive downgrade – it failed to show a benefit when combined with Novartis’s Lucentis in wet age-related macular degeneration in December (Ophthotech flop opens up Novartis nightmare scenario, December 12, 2016). By this time, though, forecasts had already fallen after a similar combo being tested by Regeneron flunked in October.
|Five biggest downgrades to marketed assets over the past 12 months|
|Product||Company||Therapy area||2020e sales ($m)||12-mth change ($m)|
|Neratinib/PB272||Puma Biotechnology||Breast cancer; kinase inhibitor||921||-1,380|
|Fovista||Ophthotech||Anti-PDGF; macular degeneration||32||-1,142|
|Lampalizumab||Roche||Anti-complement factor D; macular degeneration||543||-438|
|ITI-007||Intra-cellular Therapies||Anti-psychotic; schizophrenia||211||-434|
|CTL019||Novartis||CAR-T therapy; leukaemia||394||-337|
Roche’s dry AMD candidate lampalizumab has not had a comparable disaster, but seems to have been hit by delays, with the first data from phase III trials, begun in 2014, now not due until the second half of 2017.
Puma’s breast cancer candidate neratinib had already had problems with its side effect of severe diarrhoea, but its outlook could get even bleaker if the Aphinity trial of Roche’s rival Perjeta comes in positive – and this is now expected to read out before neratinib’s May 19 FDA action date (Event – Roche has Aphinity for Perjeta trial success, but not Puma, January 5, 2017).
Confidence in CTL019 likely waned when Novartis disbanded its cell and gene therapy unit in August. A bullish R&D day in January might have gone some way to restoring its fortunes, but too late for this analysis.
2016 was relatively quiet on R&D news, but with some important read outs set for this year, this analysis could see some bigger movements next time.