Evaluating Late-Stage Pipelines and Potential - Pharmaceutical Technology

Latest Issue

Latest Issue
PharmTech Europe

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

Inside the pipelines

Pfizer . Pfizer provided an update of its development program, which includes 118 programs from Phase I through registration, as of September 2010. The 118 programs in place was a decline compared with the 133 programs that the company had as of its previous pipeline update in January 2010. The 118 programs reflect 25 drug candidates that are new compounds or other drug that have advanced along the pipeline and 31 programs that were discontinued. The company's pipeline as of its September 2010 update included 26 programs in Phase III development, and nine programs in registration as well as 27 biologics and four vaccines within all phases in development. The company also had 46 projects in Phase I development, and 37 drug candidates in Phase II development.

Pfizer discontinued several late-stage projects when providing an update to its pipeline in September 2010. These withdrawals included several existing drugs that were being developed for additional indications: Sutent (sunitinib) for various oncology indications; Celebrex (celecoxib) for treating gouty arthritis; and Lyrica (pregabalin) for treating restless legs syndrome. The company also discontinued development of a monoclonal antibody in Phase III development, figitumumab, which was being examined for treating non-small-cell lung cancer although the drug continues to be studied for other indications.

Pfizer has several Phase III oncology drug candidates. Some key candidates include PF-00299804, an investigational, oral, pan-HER (pan-human epidermal growth factor receptor) inhibitor. It is an irreversible small- molecule inhibitor of HER-1 (EGFR- epidermal growth factor receptor)-2 and -4 tyrosine kinase designed to treat lung cancer. Neratinib also is a pan-HER inhibitor and is targeted to treat breast cancer. Bosutinib is an investigational oral dual Src and Abl kinase inhibitor. It is believed that bosutinib may inhibit Src and Abl tyrosine kinases in chronic myeloid leukemia cells that allow the cells to grow, survive, and reproduce. Axitinib is a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor designed to treat renal-cell carcinoma. And crizotinib (PF-02341066) is an anaplastic lymphoma kinase (ALK) inhibitor for treating patients with advanced non-small-cell lung cancer whose tumors are ALK-positive.

Crizotinib was granted fast-track status by FDA in December 2010. In January 2011, Pfizer initiated the rolling submission of a new drug application (NDA) to FDA for crizotinib and expects to complete the submission in the first half of 2011. Pfizer also plans regulatory submissions to FDA and the European Medicines Agency for two other investigational oncology compounds in 2011, axitinib and bosutinib, according to a Jan. 12, 2011, Pfizer press release.

Another important drug to watch from Pfizer's late-stage pipeline is tasocitinib (CP-690550), an investigational Janus kinase (JAK) inhibitor that is being investigated as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis. Pfizer reported positive Phase III results in 2010. The company said that the mechanism of action is an improvement compared with the mechanisms of other rheumatoid arthritis therapies that are directed at extracellular targets, such as pro-inflammatory cytokines. Tasocitinib targets the intracellular signaling pathways that operate as hubs in the inflammatory cytokine network. Pfizer also is studying orally administered tasocitinib in psoriasis, inflammatory bowel disease (i.e., Crohn's disease and ulcerative colitis), and organ transplant, and topical tasocitinib in both psoriasis and dry eye.

sanofi-aventis. sanofi-aventis had 49 projects in clinical development as of February 2010, of which 17 were either in Phase III, including seven vaccine projects, or pending review for marketing authorization from health authorities. These included nine new molecular entities (NMEs) in Phase III development, and one NME submitted for approval, which was subsequently approved in 2010. Jevtana (cabazitaxel), a novel investigational taxane compound that may be active in cell lines refractory to taxanes, was approved in July 2010 in the US as a second-line use in advanced hormone-refractory prostate cancer in men who have already been treated with docetaxel. The drug was recommended for approval by an EMA advisory committee in January 2011.

Several late-stage NMEs by sanofi- aventis are targeting oncology. These candidates include BSI-201 (iniparib), an investigational targeted therapy, which inhibits poly (ADP-ribose) polymerase (PARP1), an enzyme involved in DNA damage repair. Iniparib is in Phase III trials for treating patients with metastatic triple negative breast cancer (mTNBC) and squamous non-small-cell lung cancer. It also is in Phase II trials for treating patients with ovarian, uterine, and brain cancers. The drug is being developed by sanofi-aventis's subsidiary BiPar Sciences. Iniparib was granted fast-track designation by FDA for mTNBC. The regulatory submissions are planned for the first quarter 2011 in the US and the second quarter 2011 in the European Union, according to a Jan. 5, 2011, BiPhar Sciences press release.

sanofi aventis also is developing aflibercept, a fusion protein specifically designed to bind all forms of vascular endothelial growth factor-A (VEGF-A). VEGF-A is required for the growth of new blood vessels that are needed for tumors to grow and is a regulator of vascular permeability and leakage. In addition, aflibercept binds placental growth factor, which also has been implicated in tumor angiogenesis. sanofi-aventis is developing the drug for several cancer indications with the biopharmaceutical company Regeneron. In January 2011, Regeneron announced that it also started Phase III trials for VEGF Trap-Eye (aflibercept ophthalmic solution) with Bayer Healthcare and the Singapore Eye Research to treat choroidal neovascularisation of the retina as a result of pathologic myopia.


blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
| Weekly

What role should the US government play in the current Ebola outbreak?
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Jim Miller Outsourcing Outlook Jim MillerOutside Looking In
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerAdvances in Large-Scale Heterocyclic Synthesis
Jill Wechsler Regulatory Watch Jill Wechsler New Era for Generic Drugs
Sean Milmo European Regulatory WatchSean MilmoTackling Drug Shortages
New Congress to Tackle Health Reform, Biomedical Innovation, Tax Policy
Combination Products Challenge Biopharma Manufacturers
Seven Steps to Solving Tabletting and Tooling ProblemsStep 1: Clean
Legislators Urge Added Incentives for Ebola Drug Development
FDA Reorganization to Promote Drug Quality
Source: Pharmaceutical Technology,
Click here