Friday, 21 August 2009

Need for safe, effective and affordable medicines.

This blog will discuss New drug discovery and development to meet the unmet medical need of patients. Coverage includes New drugs in clinical testing, awaiting FDA or EMEA approval or newly approved drugs

Patients have the right for safe and effective medicines at affordable prices all over the world



    Denosumab (Prolia, Amgen) FDA Review & Approval
    By Krishan Maggon, Gust MEES and Knol Publishing Guild (KPG)

    Denosumab is a breakthrough fully human monoclonal antibody approved by both the FDA and EMA in 2010. It had been fast...


    Ipilimumab (BMS) Review: A Cancer Breakthrough?
    By Krishan Maggon, Gust MEES and Knol Publishing Guild (KPG)

    Ipilimumab (BMS) Review: A Cancer Breakthrough?
    Monoclonal antibody rolls back Advanced Melanoma
    A Cancer Breakthrough? Ipilimumab (MDX 010) is a fully human monoclonal antibody mAbs which has shown dramatic, sustained and complete responses in some refractory advanced melanoma patients. It was discovered and developed by Medarex (part of Bristol Myers Squibb) UltiMab technology around 1993. It has completed Phase III trials in refractory and non responding ( to prior treatment) melanoma patients. Ipilimumab has been in clinical trials for over a decade and advanced Phase II-III trials for over 7 years. The mAbs targets CTLA4 and activates treated patient's own immune system. It has doubled the 1 and 2 year survival rates in metastastic melanoma (MM) patients and may become the first new melanoma drug approved in decades. Hundreds of patients with advanced melanoma (with short life expectancy of few months) after treatment with the drug are living for more than 1-2 years. The registration dossier for MAA with the EMA was filed in May 2010 and BLA/NDA was filed with the FDA in June 2010 for MM. It has fast track and orphan drug status for the FDA and EMA review. Its blockbuster potential and use in prostate and lung cancer may once again help Bristol Myers Squibb BMS regain its leadership in the oncology market. ASCO abstracts information added. ASCO and CTLA4 Meetings 2010 data added. BMS has announced the start of Phase III trials in NSCLC. Ipilimumab created media frenzy following the release of Phase III melanoma results. The drug extended overall survival by 10 months in advanced melanoma. IPI may be approved and launched by the end of the year under fast track review. Although it is always risky to predict FDA/EMA decision, conditional approval by August-September as a life saving drug is a strong possibility.


    Bapineuzumab (Pfizer, J&J, Elan) Review
    Alzheimer's Disease Hope or Breakthrough?
    Alzheimer: Bapineuzumab is a fully humanized monoclonal antibody which targets beta amyloid protein involved in Alzheimer's Disease. There are 26 million patients in the world, half in Asia and the rest in N America/Europe with AD. It is the most advanced mAbs as well as the first new drug aimed at slowing, stopping the disease progression and degradation of the cognitive function. Johnson and Johnson paid over $ 1.5 billion for co-marketing rights to the originating company leading to mixed reactions from analysts. There are 14 ongoing Phase III trials in over 10,000 patients and results of some completed studies may be available in late 2012. The drug has fast track regulatory status with FDA. It must clearly show a beneficial and lasting effect through validated biomarker of underlying AD disease mechanism. If approved and marketed, this may be the first drug to stop disease progression and rate of decline in AD. It is hoped that clearing of beta-amyloid plaques results in slower rate of decline in cognitive and functional status of AD patients just like tumor reduction resulted in prolonged survival with cancer drugs. There are unconfirmed reports of clearing of plaques, reduction in tau proteins, progress in trials and return to "normal" of patients in early stages of AD and in clinical trials.


    Tocilizumab (Actemra/RoActemra) Review
    rheumatoid arthritis, interleukin 6, mAbs, FDA approval, EMEA approval, ADRs, sales, projections, forecast, market launch
    Actemra (Tocilizumab) is the new drug from Roche/Chugai/Genentech to be approved by the FDA in 2010. It is to treat rheumatoid arthritis patients refractory to existing drugs and is marketed in Europe. FDA rejected the advice of its advisory panel in 2008 and asked for additional data about the manufacturing controls. Reports of links to serious adverse events in Japan did not result in further delays. Roche says that the marketing uptake of the drug has been good in 8 European countries, Japan, India and Brazil with sales of $140 million in 2009. It is the first monoclonal antibody which targets Interleukin 6 and offers an alternative to 30% of arthritis patients not responding to or intolerant of TNF blockers. The cost of the drug may be in the range of $1060-2125 per month of treatment depending on the dose used. It is the 8th biologic to be approved for arthritis patients.


    Belimumab (Benlysta, HGSI, GSK) Lupus Review
    Monoclonal antibody to treat Lupus/SLE
    No new drug has been approved to treat Lupus during the past 50 years. Belimumab is one of the rare new biologics to complete 2 phase III trials meeting its primary end points and criteria of efficacy. The BLA/NDA filing is expected in the 2Q2010. However analysis of the data at 18 months showed that the efficacy of the drug was no better than placebo? Belimumab was discovered and developed by Human Genome Sciences (HGSI) and is licensed to Glaxo Smith Kline( GSK ) for European and International markets. The drug was granted fast track regulatory review in the US and Europe. HGSI and GSK have filed the dossier for Marketing Authorization Application (MAA) to the European Medicines Agency EMA containing data from the BLISS 52 and 76 studies in a total of 1684 patients and HGSI completed the BLA filing with the FDA on 10 June 2010. With the fast track regulatory review by the FDA and EMA (6 months), if the safety and efficacy data is judged sufficient, the drug may be approved and launched before the end of the year. Live RSS updates from EULAR meeting added.


    Tanezumab (Pfizer ) Review: Chronic Pain Relief
    Monoclonal antibody for Osteoarthritis pain relief
    Tanezumab (Pfizer) targets nerve growth factor IgG; the humanized mAbs is in Phase III trials for osteoarthritis pain relief and lower back pain. Large number of active Phase III trials show Pfizer management strong belief and backing for the product. Phase II data shows 50% pain reduction in over 57% of treated patients compared to only 20% for the naproxen group. The active drug is tried in different dose schedules (2.5, 5, 10 and 20 mg iv) every 8 weeks in osteoarthritis of the knee, hip, low back pain and other painful conditions. Preliminary Phase III data in 690 OA patients presented at EULAR 2010 showed significant reduction in pain scores and improvement in physical function tests at the 3 doses levels tested 2.5, 5 and 10 mg in comparison to the placebo group. Pfizer has suspended dosing and recruitment of patients in all ongoing studies in osteoarthritis, low back pain and neuropathic diabetes pain with Tanezumab. FDA put the clinical hold after reports of worsening of OA in some patients resulting in surgery and joint replacement. Trials in other indications for pain relief continue and are not affected.


    Motavizumab (Numax, MedImmune) RSV Review
    Immunoprophylaxis of Respiratory Syncytial Virus ( RSV )
    Motavizumab (Numax, MEDI 532, MedImmune/ AstraZeneca) new humanized monoclonal antibody for immunoprophylaxis of Respiratory Syncytial Virus RSV infections in premature and young babies is undergoing FDA review for approval and marketing. A brief multimedia overview of the clinical safety and efficacy of the new drug, along RSV, its economic impact, existing drugs and treatment and new drugs in development for RSV is provided.

    The registration dossier to the FDA contained Phase III data on over 6600 young infants. The RSV market is dominated by MedImmune and its monoclonal antibody Synagis with sales of $ 1.1 billion in 2009. Motavizumab if approved and marketed may replace Synagis as the treatment of choice and ward off generic threats from biosimilar palivizumab. FDA had scheduled an advisory committee meeting to discuss motavizumab on 2 June 2010. The advisory panel by a vote of 14 to 3 recommended its rejection by the FDA. Concerns were expressed at the 3-6 times rates of skin reactions and lack of clinical superiority over Synagis. The panel asked for more data and studies. FDA decision is expected under PDUFA by 24 June, 2010.

  8. Zalutumumab (HuMax-EGFR, Genmab) Cancer Review
    By Krishan Maggon and Knol Publishing Guild (KPG)
    This is the first multimedia interactive review of published data, about a new fully human monoclonal antibody Zalutumumab...

  9. Raxibacumab (ABthrax, HGS ) Review
    By Krishan Maggon, Knol Publishing Guild (KPG) and Gust MEES
    A multimedia review of the first monoclonal antibody (mAbs) to protect from inhalation Anthrax toxin is presented. Since i...


    Daclizumab (Biogen, Abbott) Review: Multiple sclerosis
    Multiple Sclerosis Hope or Breakthrough?
    Daclizumab is a humanized monoclonal antibody which targets the CD25 alpha subunit of the high affinity receptor and inhibits T cell activation. The mAbs was discovered and developed by Protein Design Lab PDL. It was the first humanized mAbs to win FDA approval in 1997 for the prevention of acute graft rejection in kidney transplant patients. The drug was marketed by Roche as Zenapex until 2008 . The annual sales were low and it was withdrawn from the market for commercial reasons in 2009. It is one of the most advanced mAbs as well as the one of the new drugs aimed at slowing, stopping the disease progression and degradation of the axon protective myelin sheath destruction in multiple scelrosis. There are ongoing Phase III trials in MS patients and results of some completed studies may be available in late 2012. The drug has fast track regulatory status with FDA. It must clearly show a beneficial and lasting effect through validated biomarker of underlying MS disease mechanism. It is hoped that clearing of MS plaques may results in slower rate of decline in nerve fibers destruction and improve functional status of MS patients just like tumor reduction resulted in prolonged survival with cancer drugs. This is the first multimedia review of daclizumab in multiple sclerosis. FDA advisory committee has recommended approval of Gilenia (fingolimod, FTY720) the first oral drug for MS on June 10, 2010 under REMS. Global market and sales data for 2009 MS market has been added.


    Teplizumab (MacroGenics, Lilly) Diabetes Review
    Monoclonal antibody (Anti CD3) for Type I Diabetes Cure or Hype?
    Diabetes is the real pandemic of our times with 285 million patients and 4 million deaths worldwide in 2009. Lifelong insulin replacement therapy is the life saving treatment which generated over 14 billon dollars in sales in 2009. Development of disease modifying drugs to treat the underlying cause of diabetes is a high priority industrial R&D objective. Teplizumab is a humanized monoclonal antibody acting on the CD3 to suppress the T cell activation and immune system. Phase II trials indicate that 12-14 days infusion with teplizumab reduces auto destruction of insulin producing beta islet cells for upto 1 year and even upto 5 years in few patients. Teplizumab is in Phase III trials in Type I diabetic patients. Immunosuppression by vaccines, mAbs and immunosuppressive drugs offer a new hope to cure diabetes and stop its complications. The present review covers the diabetic market, global insulin market, new disease modifying drugs in R&D and published clinical results of Teplizumab.

  12. Pagibaximab ( Biosynexus, GSK ) Review: Sepsis
    By Krishan Maggon, Gust MEES and Knol Publishing Guild (KPG)
    Pagibaximab (Biosynexus, Glaxo Smith Kline) is a chimeric (murine/human) monoclonal antibody which targets anti lopoteicho...


    Farletuzumab ( Eisai) Cancer Review
    By Krishan Maggon, Knol Publishing Guild (KPG) and Gust MEES
    Farletuzumab (Morphotek, Eisai) is an antifolate receptor alpha mAbs in clinical Phase III trials in ovarian cancer patien...

  14. PLX 4032 (Plexxikon, Roche) Melanoma Review
    BRAF V600E inhibitor targeted therapy for advanced melanoma
    Only a single new investigation drug has produced a 70% response rate and extended overall survival by 9 months in a Phase I trials in advanced melanoma. The active compound in question does not have a name yet and has only a code name. PLX 4032 is a BRAF gene mutaton inhibitor which may herald the era of personalized therapy for melanoma patients. It seems to work in patients who test positive for the gene mutation. In BRAF V600E gene mutation +ve patients it resulted in tumor regression and increased survival varying by few months and had complete and partial responses. However all the patients had relapse and progressive disease after a period of PFS. PLX 4032 is one of the rare drug to go directly in Phase III trials without completion of Phase II BRIM 2 trial. The clinical dose in Phase II and III trials is 960 mg oral twice a day. Active BRIM 3 trial is ongoing in 100 sites in US, Canada, Europe and Australia with each site expected to enroll between 10-20 patients. The product does not work in patients without BRAF gene mutation and failed to show activity in colon cancer patients with +ve gene mutation. A combination trial with Ipilimumab is planned in braf gene positive melanoma patients.

  15. Stem Cell Therapy Market
    New Era for Regenerative Medicine
    It has taken 12 years after the isolation of human embryonic stem cells to move from discovery to human clinical trials in the US. FDA approval of Phase I trial for Geron embryonic stem cells for spinal cord injury is a milestone. FDA had approved the start of Phase I trials with human neural stem cells in 2008. Taking the analogy from monoclonal antibodies, the first stem cell treatment may reach the market by after 2018. The attrition rate of new technology and therapy is much higher for the first generation products. If stem cell treatment pass the current criteria for safety and efficacy in clinical trial and are not associated with any new toxicity or risk, then a new market opportunity is created. There were more than 50 biotechnology companies were active in stem cell research and therapeutic development and over 40 active clinical trials in Europe. The market value of these companies was $2 billion in mid 2010. FDA/EMA regulatory guidelines and regulations are evolving to ensure the safety of the products in clinical testing. Several of the first generation investigational cells have received fast track and orphan drug designation from the FDA/EMA. Like the monoclonal antibody market of $ 40 billion in 2009, stem cell therapy may generate similar revenues 12 years after first approval and give rise to several blockbuster products. The first stem cell MAA dossier may be filed for approval with EMA in 2010 and likely to be approved first in Europe during 2011.

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