Evaluating Late-Stage Pipelines and Potential - Pharmaceutical Technology

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Evaluating Late-Stage Pipelines and Potential
Will 2011 be a more promising year for new molecular entities? A review of Big Pharma's late-stage pipeline shows what might lie ahead.

Pharmaceutical Technology
Volume 35, Issue 2, pp. 52-56

Other late-stage drugs by sanofi include: ombrabulin (AVE8062), which is currently being investigated in Phase III for treating refractory advanced soft tissue sarcoma. Phase III studies also are planned in non-small-cell lung cancer. Another late-stage candidate is alvocidib, a cyclin-dependent kinase (CDK); CDKs are involved in both cell-cycle progression and transcription. sanofi aventis also is partnered with the Danish biopharmaceutical firm Zealand Pharma for lixisenatide, a glucagon-like peptide-1 (GLP-1) drug to treat diabetes. sanofi also is developing otamixaban, an anti-Xa intravenous anticoagulant.

Novartis . Novartis reported in November 2010 that it has 142 pipeline projects in pharmaceuticals at various stages of clinical development, of which more than 35% are in Phase III or registration. The company plans to submit 30 regulatory submissions in pharmaceuticals before the end of 2012, inclusive of NMEs as well as additional indications for existing drugs or new formulations.

Novartis was targeting to complete eight regulatory submissions in 2010. These candidates included: a single-pill combination for Tekturna (aliskiren) and amlodipine for treating hypertension; Lucentis (ranibizumab) for treating visual impairment due to macular edema secondary to retinal vein occlusion; Afinitor (everolimus) for treating subependymal giant-cell astrocytoma associated with tuberous sclerosis; and SOM230, an investigational compound to treat Cushing's disease. In 2011, Novartis expects to complete a further 13 regulatory submissions with an additional nine planned for 2012, according to a Nov. 17, 2010, Novartis press release.

Novartis experienced a setback in its pipeline when it decided in October 2010 to discontinue development of two compounds: albinterferon alfa-2b, a drug being developed with Human Genome Sciences to treat chronic hepatitis C, and Mycograb (efungumab), an antifungal agent. The company took an impairment charge of $590 million in the third quarter 2010 for discontinuing these programs, $230 million for stopping development of albinterferon alfa-2 and $360 million for stopping development of efungumab.

GlaxoSmithKline (GSK) . GSK has approximately 30 drug candidates in late-stage development, according to a January 2011 company overview of its portfolio, and the company recently highlighted progress on some of those candidates. In January 2011, GSK started two global Phase III studies in patients with advanced or metastatic melanoma that have a BRAF V600 mutation. The studies will separately assess the efficacy and safety of two investigational agents, GSK2118436 and GSK1120212, to determine their individual ability to stop or slow the progression of skin cancer in patients whose tumors contain a BRAF V600 mutation, which the company said occurs in 50–60% of melanoma patients. GSK also will evaluate these compounds alone and in combination with other agents in other difficult-to-treat forms of cancers, including pancreatic cancer, refractory or relapsed leukemia, and other solid tumors.

Also in January 2011, GSK received a positive recommendation from EMA for Trobalt (retigabine) as an adjunctive treatment for partial onset seizures (i.e., a form of epilepsy where a seizure begins in a specific area in one side of the brain), with or without secondary generalization in adults aged 18 years and older with epilepsy. Retigabine received preliminary approval from the Swiss Agency for Therapeutic Products, Swissmedic, in December 2010. Retigabine, referred to as ezogabine in the US, is being jointly developed by GSK and Valeant.

GSK also began Phase III studies for GSK2402968, an antisense oligonucleotide, to treat a neuromuscular disease, Duchenne muscular dystrophy in ambulant boys who have a dystrophin gene mutation amenable to an exon 51 skip. The drug was granted orphan- drug status in the EU and US and is being developed as part of an alliance between GSK and Prosensa.

Roche . Roche's late-stage pipeline includes potentially 10 regulatory submissions of NMEs through the end of 2013, according to a Dec. 9, 2010, Roche press release Some key compounds are T-DM1 (trastuzumab) and pertuzumab for treating breast cancer and GA101/RG7159, a glyco-engineered Type II humanized anti-CD2-monoclonal antibody to treat relapsed/refractory aggressive non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Aleglitazar is being developed to treat cardiovascular risk in patients with Type II diabetes, and dalcetrapib is being developed to reduce cardiovascular risk and dyslipidemia. RG1678, a glycine-reuptake inhibitor, is being developed to treat the negative symptoms and suboptimally controlled positive symptoms of schizophrenia.

Roche also is evaluating the progress of late-stage compounds to move them either to Phase III development or possible registration. Some compounds include RG7204, which is designed to selectively inhibit the mutated BRAF protein, which can be found in certain cases of metastatic melanoma. MetMAB, a monovalent antibody, is being developed to treat solid cancers. Ocrelizumab, a humanized anti-CD20 antibody, is being studied to treat multiple sclerosis, and RG7201 and taspoglutide are being examined as treatments for Type II diabetes.


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