Unanimous FDA panel votes in favour of biosimilar versions of Avastin and Herceptin need not be reasons for Roche to panic just yet. Legal wrangling in the biosimilar world has meant that of the five copycat monoclonal antibodies approved in the US, only one, Pfizer’s Remicade biosimilar Inflectra, has been launched.
Still, Roche cannot delay the inevitable forever, and the eventual entry of biosimilars could put a sizeable dent in Avastin and Herceptin’s combined $14bn sales. And worryingly for the Swiss company, its current pipeline does not look capable of picking up the slack. Of the projects with EvaluatePharma sellside consensus forecasts attached, only lampalizumab and crenezumab come close in terms of peak sales (see tables below).
|MAb biosimilar status in the US|
|Phase I||Phase II||Phase III||Submitted||Approved||Marketed|
|Avastin||1||-||4||1 - Allergan/Amgen||-||-|
|Enbrel||-||2||-||-||1 - Novartis||-|
|Herceptin||1||-||3||1 - Mylan/Biocon||-||-|
|Humira||-||-||7||1 - Boehringer||1 - Amgen||-|
|Remicade||1||1||2||1 - Pfizer||2 - Samsung and Celltrion||1 - Pfizer|
Crenezumab is particularly risky as a potential replacement after its failure in phase II, as well as late-stage blow-ups with other anti-amyloid MAbs in Alzheimer’s disease. Roche still hopes that targeting earlier-stage disease will eventually lead to success, and in February started a second phase III trial in prodromal to mild Alzheimer’s.
Roche also has gantenerumab, another project targeting beta-amyloid, but with a slightly different mechanism of action. It is also in two phase III trials with results due in the next couple of years. However, Barclays analysts only give crenezumab and gantenerumab a respective 10% and 5% chance of success. With Alzheimer’s drug development notoriously tricky, Roche would be unwise to pin its hopes here.
|Roche's mid-to-late stage pipeline|
|Global sales estimate ($m)|
|Project||Indication||Pharmacology class||2022||Peak sales|
|Lampalizumab||Dry age-related macular degeneration||Anti-complement factor D MAb||1,210||4,499|
|Emicizumab||Haemophilia A||Anti-factor IXa/X bispecific MAb||1,007||-|
|Etrolizumab||Ulcerative colitis, Crohn's disease||Anti-beta 7 integrin MAb||439||1,500|
|Polatuzumab Vedotin||Non-Hodgkin lymphoma||Anti-CD79 MAb-monomethyl auristatin E conjugate||119||1,500|
|Crenezumab||Alzheimer's disease||Anti-beta-amyloid MAb||87||4,499|
|Taselisib||Breast cancer||Phosphatidylinositol 3-kinase inhibitor||75||1,250|
|Idasanutlin||Acute myeloid leukaemia||Murine double minute 2 inhibitor||48||-|
|Gantenerumab||Alzheimer's disease||Anti-beta-amyloid MAb||43||-|
|RG6168||Optic neuromyelitis||Anti-IL-6 MAb||24||-|
|Danoprevir||Hepatitis C||Hepatitis C NS3/4A protease inhibitor||3||-|
|RG6046||Breast cancer||Selective oestrogen receptor degrader||101||-|
|RG7314||Autism spectrum disorders||Vasopressin 1a receptor antagonist||55||-|
|RG7716||Wet age-related macular degeneration||Vascular endothelial growth factor A & angiopoietin 2 MAb||54||-|
|Lebrikizumab||Eczema/dermatitis, idiopathic pulmonary fibrosis||Anti-IL-13 MAb||54||1,281|
|Codrituzumab||Hepatoma||Anti-glypican 3 MAb||28||-|
|Olesoxime||Spinal muscular atrophy||Mitochondrial pore modulator||27||-|
|Ipatasertib||Prostate, breast, stomach cancers||Protein kinase B/Akt inhibitor||18||-|
Meanwhile, the consensus forecast for the dry age-related macular degeneration project lampalizumab has come down in the past year after delays to its phase III readout. Investors should finally get a look at the data in the second half of this year.
Perhaps a surer bet is the haemophilia A candidate emicizumab, which recently reported positive data from the Haven 1 and 2 trials at the International Society on Thrombosis and Haemostasis (ISTH) meeting in Berlin (Roche brings new blood to haemophilia A, June 26, 2017).
The project is now filed with the FDA and, with breakthrough therapy designation in patients who have developed inhibitors – antibodies to factor VIII – could be approved in this population by the end of the year. But with emicizumab linked with safety concerns and rival haemophilia candidates progressing – including Alnylam’s once-monthly subcutaneous injection fitusiran and gene therapies potentially on the horizon – the haemophilia market could become crowded.
Other attempts by Roche to expand its existing products into new areas have also fallen flat, with the breast cancer drug Perjeta disappointing in the adjuvant setting.
Approvals for the Avastin and Herceptin biosimilars – Amgen’s ABP 215 and Mylan’s MYL-1401O, respectively – now look imminent, but Roche might have a bit of breathing space before their launch. Even so, it looks like it needs some fresh blood.
|Gantenerumab||Mild AD phase III||NCT02051608||Jul 2018|
|Prodromal AD phase III||NCT01224106||Dec 2019|
|Cread 2||NCT03114657||Oct 2021|