Key clinical trial readouts for big pharma in the second half

Data on the Alzheimer’s disease candidates bapineuzumab and solanezumab might remain the most hotly expected clinical trial results this year, but the world’s biggest drug makers have several other late-stage candidates in the locker due to report make-or-break data before 2012 is out.

Gilead investors will be keenly awaiting further data on GS-7977, the hepatitis C candidate the company bought with Pharmasset for $11bn, and strong results are needed to justify that acquisition price. From the big pharma camp Merck & Co is looking for boosts to already-marketed products from closely watched trials of Vytorin and Tredaptive, the Improve-IT and HPS2-Thrive studies. Meanwhile Eli Lilly is awaiting results from six late-stage candidates, making this a crucial period for one the industry’s most beleaguered big pharma players (see table).

Sky high

Expectations about the commercial potential of GS-7977 might have been tempered in recent months – largely due to an increasingly competitive environment – but hopes are still sky high for Gilead’s most valuable pipeline candidate. Consensus has sales reaching $5.3bn by 2018, and the product needs to shine in pivotal studies to hope to achieve these revenues.

Due in the fourth quarter are readouts from two phase III studies, Fission and Positron, in genotype 2/3 patients, while phase II studies testing the agent in combination with other oral drugs, including Bristol-Myers Squibb’s daclatasvir, should also yield data.

Merck could have a big year end for data, although both events could slip into 2013.

The Improve-IT study, a huge 18,000-patient outcome study started in 2005, is testing whether Vytorin – a combination of a statin and a cholesterol absorption inhibitor, Zetia – is more effective at preventing cardiovascular events and deaths than using the statin alone. Sales of Vytorin dropped from a peak of $2.8bn in 2007 to $1.9bn after evidence emerged suggesting this was not the case, a scandal of withheld trial data that still taints the reputation of Merck today.

The Improve-IT study is unlikely to complete until next year but an independent monitoring board said in March that it would be conducting its next analysis in about nine months time. That means late 2012, and while few expect the results at that stage to be so overwhelmingly positive that the trial stops, there is still a slim chance that this might happen.

With many commentators expecting the trial to fail to show any benefit, a positive readout could stem declines for a fading product that is still fairly important for Merck – sales are seen reaching $1.8bn this year. Should the trial find the drug causes harm, the US company is looking at an even bigger disaster on the PR front.

Also in the cardiovascular space, the even more substantial 26,000 HPS2-Thrive study with the HDL-boosting agent Tredaptive might yield results towards the end of the year, although this could well not emerge until 2013. Again, evidence that the miacin-based product is cardioprotective would likely give a big boost to a currently insignificant product for Merck – sales reached $26m last year – and help provide valuable evidence in the ongoing HDL debate (Vantage Point - Functionality in focus as HDL hypothesis awaits confirmation, September 8, 2011).

Hard to beat

As recently discussed by EP Vantage, Eli Lilly has a big period of data readouts approaching, and as a trenchant defender of the R&D model it needs some wins. The failure of pomaglumetad a few weeks ago in phase II does not bode well for an interim look at a larger phase III study, due later this year (After Lilly shrugs off schizophrenia failure pipeline must deliver, July 12, 2012).

The Indianapolis company will be hoping that its other CNS and diabetes hopefuls deliver the goods. Data on Eli Lilly and partner Boehringer Ingelheim’s biosimilar insulin product LY2963016, a version of Sanofi’s Lantus, will be closely watched, particularly given the delay to Novo Nordisk’s new insulin entrant, degludec.

Of course the readout on solanezumab and Pfizer and Johnson & Johnson’s bapineuzumab will be hard to beat in terms of big clinical events this year, even though both are widely expected to fail to show any benefit (Event – Amyloid-targeting Alzheimer’s therapies seek crumbs of comfort, June 26, 2012).

Lilly has said that it expects to report information in the latter half of the third quarter while J&J confirmed recently that the bapi data would also come this quarter, with the first detailed presentation at a European medical conference shortly afterwards, likely the EFNS Congress in Stockholm.

Data read outs
Product Pharmacological Class Company Event- trial results Indication Date Product  NPV ($m) NPV as % of Market Cap Trial IDs
GS-7977 Hepatitis C nucleoside NS5B polymerase inhibitor Gilead Sciences II and III Hepatitis C Q3 18,398 47% NCT01260350 NCT01329978
Afinitor Rapamycin analogue (mTOR inhibitor) Novartis III Breast cancer Q4 7,004 5% NCT00876395
Vytorin Statin/ HMG CoA reductase inhibitor & cholesterol absorption inhibitor  Merck & Co III Hyperlipidaemia Q4 3,083 2% NCT00202878
Tredaptive Vitamin B3 & prostaglandin D2 receptor antagonist Merck & Co III Lipid disorders Q4 2,287 2% NCT00461630
Abraxane Taxane Celgene III Pancreatic cancer Q4 2,234 8% NCT00844649
Nexavar Multi-kinase inhibitor Bayer III Breast cancer Q3 1,985 3% NCT01234337
New insulin glargine product Insulin Eli Lilly III Diabetes Q3 1,856 4% NCT01421147
Riociguat Guanylate cyclase activator Bayer III Pulmonary hypertension Q3 1,790 3% NCT00810693
Dulaglutide GLP-1 agonist Eli Lilly III Diabetes Q3 1,081 2% NCT01064687
Pomaglumetad Methionil mGluR2/3 agonist Eli Lilly III Schizophrenia Q4 886 2% NCT01307800
LY2216684 Norepinephrine reuptake inhibitor Eli Lilly III Major Depressive Disorder Q4 819 2% NCT01185340
Bapineuzumab Anti-beta amyloid MAb Pfizer III Alzheimer's Disease Q4 770 0% NCT00575055
Bapineuzumab Anti-beta amyloid MAb Johnson & Johnson III Alzheimer's Disease Q4 491 0%
Solanezumab Anti-beta amyloid MAb Eli Lilly III Alzheimer's Disease H2 675 1% NCT00905372
Atacicept B lymphocyte stimulator & proliferation-inducing ligand  inhibitor Merck KGaA II Systemic Lupus Erythematosus Q3 461 2% NCT00624338
BI10773 (empagliflozin) Sodium-glucose cotransporter-2 (SGLT2) inhibitor Eli Lilly III Type 2 Diabetes Q4 396 1% NCT01210001
Cilengitide Integrin inhibitor Merck KGaA III Glioblastoma Q3 348 2% NCT00689221
AMG 103 Anti-CD19 MAb Amgen II ALL Q4 306 1% NCT01207388
rFVIIIFc Factor VIII Biogen Idec III Hemophilia A Q4 265 1% NCT01181128
IDegLira GLP-1 agonist & insulin Novo Nordisk III Diabetes Q4 19 0% NCT01336023
AMG 145 Anti-PCSK9 MAb Amgen II Hyperlipidaemia Q4 - - NCT01380730
Talimogene laherparepvec Oncolytic virus Amgen III Melanoma H2 - - NCT00769704

Data source: EvaluatePharma's Calendar of Events.

To contact the writer of this story email Amy Brown in London at [email protected] or Joanne Fagg at [email protected].

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