If the European regulator has sometimes given the impression of being a mere rubber-stamper of its US opposite number’s decisions, this year it certainly showed that it has a mind of its own.
And in the first half of 2013 it is the EU that will be the battleground for midcap players’ key regulatory decisions; many will concern products already given the US green light, such as Medivation’s Xtandi, Arena Pharmaceuticals’ Belviq and Ariad Pharmaceuticals’ ponatinib (see table below). Midcap pharma and biotech will thus watch eagerly for continued signs of independence of thought.
Among the drugs with the highest NPV as calculated by EvaluatePharma, it is perhaps the EU decision facing the obesity pill Belviq that should cause most concern. The read-across comes from Vivus’s competitor Qsymia, which did at long last secure US approval last year, but then fell over at the CHMP.
As far as obesity goes Europe is clearly taking a tough stance, likely relating to risk/benefit considerations. Although normally EU sales represent no more than a significant minority of revenues, the territory forms a major part of Arena’s strategy – hence the importance of the EU verdict on Belviq.
Meanwhile, Xtandi and ponatinib – highly promising cancer drugs – likely have little to fear, although investors will watch eagerly for any additional fallout from the safety issues that recently led the FDA to add a warning to ponatinib’s label (Ariad approval catches bio run-up traders by surprise, December 17, 2012).
Still, the EMA has shown that it can go boldly where the FDA fears to tread: for instance, although Pfizer’s blood thinner Eliquis was hit with a US complete response letter citing data management and verification issues the EU regulator had no qualms about giving it a clean bill of health. This stance could embolden Ariad.
Also awaiting the European green light at some point by mid-2013 is Dendreon’s hugely hyped prostate cancer autologous immunotherapy, Provenge.
US triggers too
Meanwhile, of the most important midcap US catalysts in the next six months the biggest is surely the FDA decision on Theravance’s LABA/steroid combination Breo. This will face a US panel for the COPD indication before a US decision due by March 12. Breo, formerly known as Relovair, carries an NPV of $4.1bn, according to EvaluatePharma data, and could become Theravance’s first approved drug and transform the company.
Analysts still see considerable risk, given the heterogeneity of phase III data and LABA dose concerns; it is uncertain when a US filing for asthma – a problematic indication – might later be made. Breo also faces an EU decision, under the name Relvar, for use both in asthma and COPD.
A broader consideration is that Theravance’s partner GlaxoSmithKline will likely manage the launch process carefully given the current dominance in both asthma and COPD of its own blockbuster, Advair. The companies’ follow-up COPD combination of umeclidinium and vilanterol has just been filed in the US.
Also in the US, ImmunoGen is looking forward to approval of its antibody-drug conjugate Trastuzumab-DM1, following its extension of both progression-free and overall survival in metastatic Her2-positive breast cancer. The product’s approval is a major catalyst for ImmunoGen’s partner Roche, too (Key regulatory decision for big pharma in the first half of 2013, December 20, 2012).
And rare diseases continue to feature on investors’ radars. Here, a duo of small companies – Isis Pharmaceuticals and Aegerion Pharmaceuticals – await regulatory verdicts in the tiny indication of hereditary familial hypercholesterolaemia. The latter’s lomitapide has just secured US approval – hardly surprising given its strong advisory panel endorsement – and awaits an EU ruling.
For Isis’s Kynamro, however, the jury in the US is still out. Not only was its panel backing more cautious, but to add to Isis’s woes the CHMP recently issued a negative opinion on Kynamro, citing safety concerns – another clear example that a positive US outcome is no longer a reliable indicator of the regulatory verdict on the other side of the pond.
The table below is drawn from EvaluatePharma’s Calendar of Events, and highlights some of the biggest regulatory decisions facing mid and micro-cap pharma and biotech companies in the first half of 2013.
|H1 2013 regulatory decisions, companies capitalised at <$30bn|
|Product||Company||Pharmacology class||Event||Indication||Date||Product NPV ($m)||NPV as % of Market Cap|
|Xtandi||Astellas Pharma||Androgen receptor antagonist||EU approval||Prostate cancer||Q1||7,871||33%|
|Xtandi||Medivation||Androgen receptor antagonist||EU approval||Prostate cancer||Q1||4,664||115%|
|Breo/ Relvar||Theravance||Beta 2 adrenoreceptor agonist & corticosteroid||EU (COPD, asthma), adcom (COPD), US approval (COPD||COPD, asthma||Q1, Mar 7, May 12||4,113||172%|
|Belviq||Arena Pharmaceuticals||5-HT2C (serotonin) agonist||EU approval||Obesity||Q1||2,533||124%|
|Provenge||Dendreon||Prostate cancer vaccine||EU approval||Prostate cancer||Mid-2013||2,437||296%|
|Remsima||Celltrion||Anti-tumour necrosis factor alpha MAb||EU approval||rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease and psoriatic arthritis||Q1||2,169||48%|
|Ponatinib||ARIAD Pharmaceuticals||BCR-ABL inhibitor & pan-FGFR inhibitor||EU approval||Chronic myeloid leukemia, acute lymphoblastic leukemia||Mid-2013||1,794||52%|
|Vortioxetine||Lundbeck||5-HT3 & 5-HT7 (serotonin) antagonist, 5-HT1B partial agonist, 5-HT1A agonist & 5-HT re-uptake transporter inhibitor||EU approval||Major depressive disorder||Apr||1,747||62%|
|Opsumit||Actelion||Endothelin receptor antagonist||EU approval||Pulmonary arterial hypertension||Jun||1,730||28%|
|Bronchitol||Pharmaxis||Respiratory agent||Adcom, US approval||Cystic fibrosis||Jan 30, Mar 18||1,625||406%|
|Myrbetriq||Astellas Pharma||Beta 3 adrenoreceptor agonist||EU approval||Urinary incontinence||Q1||1,598||7%|
|Trastuzumab-DM1||ImmunoGen||Anti-HER2 (ErbB-2) MAb-DM1 maytansinoid conjugate||US approval||Breast cancer||Feb 26||1,496||137%|
|Defibrotide||Gentium||Cathepsin G inhibitor||EU approval||Hepatic veno-occlusive disease||Q1||1,419||877%|
|Jetrea||ThromboGenics||Plasmin||EU approval||Vitreomacular adhesion||H1 2013||1,366||72%|
|Herceptin SC||Halozyme Therapeutics||Anti-HER2 (ErbB-2) MAb||EU approval||Breast cancer||Q1||1,101||172%|
|Levadex||MAP Pharmaceuticals||5-HT1B (serotonin) & 5-HT1D agonist||US approval||Migraine||Apr 15||914||171%|
|Nuedexta||AVANIR Pharmaceuticals||N-methyl-D-aspartate & sigma-1 agonist||EU approval||Pseudobulbar affect||Q1||778||214%|
|Cometriq||Exelixis||VEGFr2, RET & Met tyrosine kinase inhibitor||EU approval||Thyroid cancer||Mid-2013||720||84%|
|Augment Bone Graft||BioMimetic Therapeutics||Platelet-derived growth factor||US approval||Bone graft for treatment of foot and ankle fusions||May 13||686||338%|
|Xiaflex||Auxilium Pharmaceuticals||Collagenase||US approval||Peyronie’s disease||May 7||683||74%|
|Rytary||IMPAX Laboratories||Dopamine precursor & dopa decarboxylase inhibitor||US approval||Parkinson's disease||Jan 21||663||47%|
|Lyxumia||Zealand Pharma||Glucagon-like peptide 1 agonist||EU approval||Diabetes||Q1||628||185%|
|Zelrix||NuPathe||5-HT1B (serotonin) & 5-HT1D agonist||US approval||Migraine||Jan 17||418||838%|
|ChemoSAT||Delcath Systems||Alkylating agent||US approval||Metastatic melanoma in the liver||Jun 14||417||448%|
|Abilify Depot||Lundbeck||5-HT1A (serotonin) & dopamine D2 partial agonist & 5-HT2 antagonist||US approval||Schizoprenia||Feb 28||406||14%|
|Procysbi||Raptor Pharmaceutical||Cystine-depleting agent||US and EU approval||Nephropathic cystinosis||Jan 30, H1 2013||340||113%|
|Amitiza||Sucampo Pharmaceuticals||Chloride channel activator||US approval||Opioid-induced constipation||Apr||286||83%|
|Kynamro||Isis Pharmaceuticals||Apolipoprotein B-100 antisense||US approval||Homozygous familial hypercholesterolemia||Jan 29||275||26%|
|Uceris||Santarus||Corticosteroid||US approval||Ulcerative colitis||Jan 16||250||37%|
|Lomitapide||Aegerion Pharmaceuticals||Microsomal triglyceride transfer protein inhibitor||EU approval||Homozygous familial hypercholesterolemia||H1 2013||242||39%|
|Probuphine||Titan Pharmaceuticals||Opioid agonist||US approval||Opioid addiction||Apr 29||215||272%|
|Uceris||Cosmo Pharmaceuticals||Corticosteroid||US approval||Ulcerative colitis||Jan 16||192||41%|
|Lemtrada||BTG||Anti-CD52 MAb||EU approval||Multiple sclerosis||Q2||124||7%|
|Zevtera||Basilea Pharmaceutica||Cephalosporin||EU approval||Community-acquired and hospital-acquired pneumonia||Feb||98||23%|
|Zaltrap||Regeneron Pharmaceuticals||VEGFr kinase inhibitor||EU approval||Colorectal cancer||Q1||90||1%|
|Crofelemer||Salix Pharmaceuticals||Cystic fibrosis transmembrane conductance regulator channel & calcium-activated chloride channel blocker||US approval||HIV-associated diarrhea||Q1||85||3%|
|Stendra||VIVUS||Phosphodiesterase V inhibitor||EU approval||Erectile dysfunction||Q1||55||4%|
|Serada||Depomed||GABA agonist||Adcom, US approval||Menopause||Mar 4, May 31||46||14%|