Midcap players ask Europe to bring it on in 2013

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.

Tough stance

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%

To contact the writers of this story email Jacob Plieth or Joanne Fagg in London at news@epvantage.com or follow @JacobEPVantage and @JoEPVantage on Twitter

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