Key data readouts in the second half of 2012

The second half of the year holds some important data readouts for the industry’s smaller players in both oncology and the much rarer orphan diseases.

While both Clovis and AB Science are studying drugs in the notoriously hard-to-treat pancreatic cancer, Amicus, Swedish Orphan Biovitrium and Biomarin are anticipating results in Fabry disease, haemophilia A and Morquio Syndrome, respectively.

Other results include Oncolytics’ attempt to treat head and neck cancer with an oncolytic virus and Active Biotech’s antibody for renal cell cancer. Rheumatoid arthritis continues to feature in the second half of the year for MorphoSys while the rollercoaster ride continues for Resverlogix with its second attempt to get its atherosclerosis approach to work (see table).

Cancer read outs

Oncolytics is awaiting interim phase III results of its lead product, head and neck cancer treatment Reolysin. The trial uses Reolysin in combination with carboplatin and paclitaxel and the results could validate the company’s approach of using a Ras-activated oncolytic virus to fight cancer.

Despite limited success of oncolytic virus-based drugs, which have all previously fallen at phase III, expectations around the drug are high with 2018 forecast sales of $911m (Event - Oncolytics prepares for big test with cancer data, April 16, 2012).

In June a data monitoring committee recommended continued enrolment in the study after reviewing safety data. The company plans to enrol between 100 and 400 patients in the second stage of the trial; the first stage included 80 patients.

Top line phase II results of Clovis Oncology’s biggest growth driver CP-4126 are expected in the fourth quarter (Clavis making hay while sun shines on cancer candidate, January 18, 2012).

The company, which licensed the drug from Clavis Pharma back in 2009, is testing the drug in a subset of pancreatic cancer patients whose tumours express low levels of a cell surface transporter called hENT1. hENT1 is a dominant transporter for gemcitabine, the current standard of care in inoperable pancreatic cancer, and tumours with low levels of the transporter have shown to be resistant to gemcitabine therapy.

In a phase II trial in 21 patients, those treated with CP-4126 lived for median 9.1 months versus 3.3 for those treated with gemcitabine. The big test is yet to come with top-line survival data from the Leap study in 360 patients, 64% of which were classified as hENT-1 low.

AB Science is expecting phase III results from its oral tyrosine kinase inhibitor AB1010 (masitinib) in advanced metastatic pancreatic cancer. The trial in 350 patients compares masitinib in combination with gemcitabine to placebo and gemcitabine with overall survival as the primary endpoint (Event - AB Science awaiting first test of scattergun approach, September 22, 2011).

Masitinib has already shown positive results in gleevec-resistant GIST: after 18 months 82% of patients treated with the drug were still alive versus 33% of those treated with Sutent.

Results of the pancreatic trial were due to be released in April this year. However the company announced a postponement because data analysis, and in particular genetic data analysis, was taking longer than expected. Analysts at Edison note that characterising a sub-population would be significant for the drug.

Results of Active Biotech’s renal cell cancer MAb Anyara are expected in the second half of the year (Active gets boost as pipeline hopes rise, May 22, 2012).

The binary phase II/III trial is studying the effect of Anyara in combination with interferon-alpha compared with interferon-alpha alone in patients with advanced renal cell cancer. With a primary endpoint of overall survival, 384 deaths will trigger the final analysis.

Based on a small phase I trial in just 53 patients analysts at Jefferies are assuming only a 20% probability of success in renal cancer, while analysts at JP Morgan note that the drug would be entering a crowded field if successful.

Niche targets

After Biomarin’s recent cash call phase III results are eagerly anticipated for its biggest predicted growth driver GALNS, due in the fourth quarter of the year. The enzyme replacement therapy would be the first to treat Morquio A Syndrome, a lysosomal storage disorder that causes difficulties with walking and breathing, hearing loss and heart valve disease (BioMarin needs to follow cash call with clinical successes, June 1, 2012).

The phase III trial, which recruited 176 patients,12 more than planned, is testing a dose at weekly and fortnightly administration for a period of 24 weeks. The primary endpoint is the six-minute walk test.

In the phase I/II extension study with total follow up of two years, patients maintained improvement in the walk test, stair climb and pulmonary function. Although the median walking distance declined from 42 meters to less than 3, which raises questions about the long-term effectiveness of the drug, some believe the decline seen could be due to the progressive nature of the disease.

Amicus Therapeutics is expecting the results from its Fabry disease drug Amigal in the third quarter.

Analysts at JP Morgan believe that the phase III monotherapy has a high probability of success and should be a transformational catalyst for Amicus.

GSKs interest in the company has recently expanded, mainly due to its Fabry disease drug, with Amicus responsible for the full commercialisation of the drug in the US (Event – Glaxo endorsement puts focus on Amicus phase III result and more, July 19, 2012).

For Swedish Orphan Biovitrium phase III results of its biggest growth driver, haemophilia A treatment rFVIIIFc, are expected in the second half of the year. The drug, partnered with Biogen Idec, is a fully recombinant clotting factor.

The long acting drug has the potential to reduce the frequency of dosing for haemophilia A sufferers. In phase I/II trials disclosed last year the drug had a half life 1.7 times that of market leader Advate (Therapeutic focus - Long-acting haemophilia agents set to shake things up, July 26, 2011).

The phase III study called A-long has enrolled 165 patients measuring the median annualised number of bleeding episodes. The company also recently announced the start its paediatric clinical trial in haemophilia A.

Further results

In rheumatoid arthritis Phase Ia/IIb results are expected from MOR103. The drug is wholly owned by MorphoSys and is an antibody directed against granulocyte-macrophage-colony stimulating factor, an inflammatory mediator. Results are due in the third quarter, if positive they could lead to a licensing deal for the company.

Canadian Resverlogix’s lead compound RVX-208 is expected to report top line results from a phase IIb study in the third quarter. The company describes the drug as the first known BET Bromodomain inhibitor to be studied in humans. It works by raising apolipoprotein A-I (ApoA-1) production leading to enhanced reverse cholesterol transport, in the hope of treating atherosclerosis.

Back in 2010 the drug failed to increase levels ApoA-1 sufficiently, but there were significant increases in HDL, known as ‘good cholesterol’, prompting the company to have another go at success (AHA 2010 – Resverlogix falls back to earth, November 18, 2010).

In the phase IIb Sustain trial, 172 patients received standard of care (including Lipitor or Crestor) and 200 mg/day RVX-208 or placebo for 24 weeks. Dosing completed in May and success second time round could mark a turnaround for the company.

In the first quarter of next year top line results from the parallel phase IIb trial Assure will be reported. This trial uses intravascular ultrasound to study the regression of atherosclerotic plaques with RVX-208 treatment.

Data read outs
Product Pharmacological Class Company Event- trial results Indication Date Product  NPV ($m) NPV as % of Market Cap Trial IDs
Reolysin Oncolytic virus - Ras activated Oncolytics Biotech III Head and neck cancers H2 2,693 980% NCT01166542
Plecanatide Guanylate cyclase type-C receptor agonist Synergy Pharmaceuticals III Chronic idiopathic constipation Q4 2,655 907% NCT01429987
GALNS N-acetyl-galactosidase-6-sulfatase BioMarin Pharmaceutical III Morquio Syndrome Q4 799 15% NCT01275066
Vosaroxin Naphthyridine analogue Sunesis Pharmaceuticals III AML H2 769 494% NCT01191801
Allovectin-7 HLA-B7 gene therapy Vical III Melanoma Q4 678 216% NCT00395070
CP-4126 Pyrimidine analogue Clovis Oncology II Pancreatic cancer Q4 639 113% NCT01124786
Naloxegol Mu opioid antagonist Nektar Therapeutics III Opoid induced constipation H2 610 63% NCT01309841
Zymafos Alkylating agent ZIOPHARM Oncology III Soft tissue sarcoma H2 590 122% NCT01168791
GRN163L Telomerase inhibitor Geron II Breast Cancer and NSCLC Q4 476 228% NCT01256762
TZP-102 Ghrelin agonist Tranzyme Pharma II Diabetic gastroparesis Q4 449 405% NCT01452815 
CXA-201 Cephalosporin & beta-lactamase inhibitor Cubist Pharmaceuticals III Urinary tract infections Q4 310 12% NCT01345929 
Amigal Alpha galactosidase chaperone Amicus Therapeutics III Fabry disease Q3 309 110% NCT00925301
OMS302 Anti-inflammatory agent & anti-cholinergic Omeros III Intra-ocular lens replacement surgery H2 256 105% NCT01579565
rFVIIIFc Factor VIII Swedish Orphan Biovitrum III Hemophilia A H2 202 20% NCT01181128
Arbaclofen placarbil GABA agonist XenoPort III Spasticity in MS Q3 183 78% NCT01359566 
QVA149 LAMA & LABA Vectura III COPD H2 108 28% NCT01490125
Zerenex Phosphate binder Keryx Biopharmaceuticals III Hyperphosphatemia H2 102 70% NCT01191255
OMS103HP Anti-inflammatory agent & analgesic Omeros III Postoperative pain H2 69 28% NCT01406561
Prochymal Mesenchymal stem cell Osiris Therapeutics II and III Acute Myocardial Infarction and Crohn's disease and Q4 57 17% NCT00877903
AZD9773 Anti-tumour necrosis factor alpha TNFa polyclonal MAb BTG II Sever sepsis H2 55 3% NCT01145560
Anyara Anti-5T4 MAb-SEA/E-120 toxin conjugate Active Biotech III Renal cancer H2 9 2% NCT00420888
AB1010 c-kit tyrosine kinase & platelet-derived growth factor receptor inhibitor AB Science III Pancreatic cancer Q3 - - NCT00789633
ADX71149 mGluR2 agonist Addex Therapeutics II Schizophrenia Q3 - - NCT01323205
BVF-036 5-HT2A (serotonin) antagonist ACADIA Pharmaceuticals III Parkinson's disease Q3 - - NCT01174004
Cevira Photodynamic therapy Photocure II HPV infections H2 - - NCT01256424
MOR103 Anti-GM-CSF MAb MorphoSys II RA Q3 - - NCT01023256
RVX-208 Apolipoprotein A-I enhancer Resverlogix II Atherosclerosis Q3 - - NCT01067820
Talactoferrin Immunomodulator Agennix III NSCLC Q3 - - NCT00707304

Data source: EvaluatePharma's Calendar of Events.

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

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