Recombinant human IGF-1, Increlex, receives marketing approval in Europe

According to a press release issued August 8, 2007, Tercica, Inc. announced that the European Commission has granted marketing authorization for Increlex(R) (mecasermin) 10 mg/ml solution for injection for the treatment of children and adolescents with short stature caused by primary insulin-like growth factor-1 (IGF-1) deficiency.

 Increlex was approved in the US in August 2005 and will now be available to children in Europe.  The European approval gives Tercica’s partner, Ipsen exclusive marketing rights in Europe for 10 years (Orphan Drug designation).

Tercica believes that there are approximately 6000 children in the U.S. and 6000 children in Europe who would be candidates for Increlex.  This drug provides an important example of the utility of the Orphan Drug Act, which provides incentives for companies to develop drugs for extremely rare diseases, such as Primary IGFD.

Best,

Healogica MD

Orencia for Juvenile Idiopathic Arthritis: FDA accepts supplemental biologics application

A press release issued by Bristol-Myers Squibb announced on August 7, 2007 that the U.S. FDA has accepted a supplemental biologics application (sBLA) for Orencia (abatacept) for the treatment of Juvenile Idiopathic Arthritis.  The acceptance of the sBLA puts Orencia on the path for approval for treatment in this patient population.

Part of the CTLA4-Ig class of drugs, Orencia was FDA approved in December 2005 for the treatment of adult patients with moderate to severe rheumatoid arthritis.  The CTLA4-Ig mechanism of action was described in a published paper in the New England Journal of Medicine (November 13, 2003) whose authors decribed the mechanism:

CTLA4Ig binds to CD80 and CD86 on antigen-presenting cells, blocking the engagement of CD28 on T cells and preventing T-cell activation.

Basically, Orencia prevents the inflammation-causing T-cell from being activated.  We’re encouraged by this preliminary step in the process of getting this drug approved and on the market for children with juvenile idiopathic rheumatoid arthritis.

Healogica MD

FDA News Release: Ongoing safety review of Prilosec and Nexium

On August 9, 2007, the US Food and Drug Administration issued a statement that it is undergoing a safety review of the popular drugs, Prilosec (omeprazole) and Nexium (esomeprazole), both made by Astra Zeneca.  To quote directly from the statement:

 ”At this time, FDA’s preliminary conclusion is that collectively, these data do not suggest an increased risk of heart problems for patients treated with omeprazole or esomeprazole.  Therefore, FDA does not believe that healthcare providers or patients should change either their prescribing practices or their use of these products at this time.”

Prilosec (which is available over the counter in the U.S. without a prescription) and Nexium (which is the L-isomer of Prilosec) are part of the proton pump inhibitor (PPI) class of drugs used to treat frequent heartburn, gastroesophageal reflux disease, peptic and duodenal ulcers.  Other drugs in this class include Prevacid, Protonix, Aciphex.

For patients with chronic conditions, such as Barrett’s esophagus, Zollinger-Ellison syndrome, and gastrinomas, the safety concern with long-term proton pump inhibitor therapy does raise some alarm, as these patients typically require life-long PPI therapy.

On May 29, 2007, AstraZeneca sent data from two long-term clinical trials in which patients taking Prilosec or Nexium may have increased risk for heart attacks, heart failure and cardiac sudden death.

While it is encouraging that the FDA has issued a preliminary statement indicating no increased risk of heart-related adverse events in patients taking Prilosec and Nexium, we are eager to follow this story to a more definitive conclusion.

Healogica MD

Meta-analysis: Statins and the risk of colorectal cancer

An interesting meta-analysis in this week’s JCO (yes, we find a lot of the studies in JCO to be interesting) studied the risk of developing colorectal cancer in patients taking the widely popular class of cholesterol-lowering drugs, statins.  The authors mention in the beginning of the article that statin use is hypothesized to reduce the risk of developing colorectal cancer.

The authors analyzed 18 studies with over 1.5 million patients taking statins and conclude that, based on this meta-analysis, statins do not reduce the risk of developing colorectal cancer.

While we feel that meta-analyses have their role in elucidating trends in clinical trials, we believe that a more definitive approach to determine the role of statins and the risk of colorectal cancer would be to conduct a prospective, double-blind, placebo-controlled randomized clinical trial.  It is doubtful that this trial will ever be done, so this meta-analysis is a useful data point for physicians and patients to consider.

Healogica MD

JCO review article: Reversibility of heart failure in patients taking Herceptin called into question

A review article in this week’s JCO examines data on cardiotoxicity (in particular, congestive heart failure) related to the use of Herceptin (trastuzumab) in the adjuvant setting.

 Data presented at the 2005 annual ASCO meeting, demonstrated a clear survival benefit in those operable HER-2+ breast cancer patients taking Herceptin and chemotherapy after surgery.  However, it is known that Herceptin causes, as one of its side effects, congestive heart failure (CHF).  Herceptin’s cardiotoxicity combined with that of anthracyclines (commonly used chemotherapy agent for breast cancer) pose significant challenges for breast cancer patients and the physicians who treat them.

 Up to 4% of patients enrolled on the adjuvant Herceptin trials experienced severe heart failure, and some 14% patients in the NSABP B-31 trial had to discontinue Herceptin due to decreases in LVEF (left ventricular ejection fraction).

The authors of this review article conclude that while adjuvant Herceptin provides “substantial benefits” in HER-2+ breast cancer patients, congestive heart failure remains a significant concern and recommend that these patients continue long-term close cardiac follow-up.

A comprehensive study in JCO Nov. 2005 delves into the potential for the reversibility of cardiotoxicity in patients taking Herceptin. 

We are most interested in following these studies for long-term cardiotoxicity.

Healogica MD

Journal of Clinical Oncology: Combination Iressa and Vioxx in relapsed metastatic non-small cell lung cancer

In last week’s Journal of Clinical Oncology, there was a Phase I/II study published on the combination of Iressa (gefitinib) and Vioxx (rofecoxib) in patients with metastatic non-small cell lung cancer whose disease progressed despite treatment with platinum-based chemotherapy.  To summarize:

• 45 patients with metastatic non-small cell lung cancer (NSLC) who had relapsed despite platinum chemotherapy were given combination Iressa and Vioxx
• one complete response and two partial responses; 12 patients with stable disease
• median time to tumor progression was 55 days; median survival was 144 days

The rational for this study is based on data that epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) play an important role in development of the tumor. 

However, it is interesting to note that Merck voluntarily pulled Vioxx from the market in September of 2004 due to an increased risk of cardiovascular events (heart attack and stroke) and that Astra-Zeneca announced in June 2005 that no new patients would be given Iressa unless part of a clinical trial due to lack of survival benefit in the ISEL trial.

We would be interested if investigators would pursue the EGFR / COX-2 approach and combine another EGFR inhibitor, Tarceva (erlotinib) with another COX-2 inhibitor, Celebrex (celecoxib) in a similar Phase I/II study.  Both of these drugs are approved and on the market.

Healogica MD

U.S. Court of Appeals Rules Against Early Experimental Drug Access For Terminally Ill Patients

The U.S. Court of Appeals for the District of Columbia Circuit ruled today (.pdf ruling) that terminally ill patients do not have a constitutional right to access new drugs that have only gone through safety testing in early stage clinical trials (AP, Bloomberg) but have yet to be approved.

A patient advocacy group called the Abigail Alliance sued the Food and Drug Administration (FDA) four years ago in an attempt to get the agency to provide access to new drugs after the drugs have been passed through initial Phase I clinical trial safety testing in human subjects.  Commonly, drugs must pass through two additional phases of clinical trials testing (taking up to 15 years in total) before they can be shown to be “safe and effective” and can be approved by the FDA for use in patients.

For now patients with terminal illnesses will have to rely on clinical trials and special “expanded access” programs sponsored by the FDA to get access to new drugs for diseases with no effective treatments.  Healogica will try to bring you as much information as possible about new treatments for a range of illnesses to help you if you are in need.  In the meantime, Frank Burroughs (the president of the Abigail Alliance) indicated that he would take his fight for patients to the Supreme Court.

Healogica MD

Journal of Clinical Oncology: Combination Xeloda and Herceptin in metastatic HER-2 breast cancer

A Phase II study published in this week’s Journal of Clinical Oncology demonstrates that the combination of Xeloda (capecitabine) and Herceptin (trastuzumab) is highly active in patients with HER-2 overexpressing metastatic breast cancer previously treated with anthracyclines and/or taxanes (e.g. Taxol).

• Phase II study of 27 patients with HER-2 overexpressing metastatic breast cancer previously treated with anthracyclines and / or taxanes
• all 27 patients given combination Xeloda and Herceptin
• Objective response in 12 patients (45%) - complete response in 4 patients (15%) and partial response in 8 patients (30%)

It will be interesting to see a Phase III study in the same patient population with combo Xeloda / Herceptin vs. each agent alone. 

Healogica MD

New HIV/AIDS medication approved

Pfizer announced yesterday that the U.S. Food and Drug Administration approved maraviroc, known as Selzentry, for the treatment of HIV/AIDS. 

 According to an article by Bloomberg News, Selzentry will be available sometime next month and will be priced at approximately $900 / month wholesale.

Selzentry joins Fuzeon as a drug that blocks the entry or fusion of the HIV virus into CD4+ T cells.  In the case of Selzentry, the drug binds to the cell membrane protein, CCR5, preventing the HIV virus from entering the T-cell.  Adding to the existing armamentarium of HIV drugs (protease inhibitors, nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors), Selzentry offers patients with resistant HIV an option for further effective treatment.

Selzentry was approved based in large part on data from two clinical trials - MOTIVATE 1 and MOTIVATE 2.

Healogica MD

Austrian company starts Phase I trial for Alzheimer’s vaccine

A recent article in the Pipeline Review announced the initiation of a Phase I trial with a new vaccine for Alzheimer’s disease.  The vaccine’s name is Affitope AD01 and is being tested by Affiris, an Austrian biotechnology company.  To summarize:

• phase I trial being run out of Vienna General Hospital
• up to 24 patients with “mild to moderate” Alzheimer’s disease to be given Affitope AD01 vaccine
• patients are to be vaccinated four times over three months
• patients are to be followed for six months
• the purpose of this phase I study is to assess the safety of Affitope AD01

While this study is in the earliest clinical phase, we’re interested in following the progress of this vaccine, as there has been no vaccine approved for Alzheimer’s disease to date.  Other vaccines in clinical development include Wyeth and Elan’s AAB-001 (Bapineuzumab), which is currently in Phase II investigation.

 Elan previously terminated a Phase IIa study with another vaccine, AN-1792, when patients were found to develop encephalitis.

Healogica MD