This is the first in a continuous series of articles that will summarize selected clinical trial plans and, more often, trial results. A brief overview of the FDA approval process is presented first and will not be repeated in future articles.
The first step of the new drug development process is referred to as the preclinical or drug discovery phase. Researchers look for compounds that may be effective in treating or preventing disease by utilizing advances in molecular biology, computer science, chemistry or other factors. Once scientists have identified a promising agent, the compound must be exposed to live animals, often rodents. This is used to show that it is safe in mammals. The results of these animal tests are used to support the filing of an Investigational New Drug (IND) application. The IND application is accompanied by chemical composition data and manufacturing information, animal testing results, the basis for testing in humans and a plan for clinical testing. Approval of the application allows the firm to design and proceed to Phase 1 trials.
Phase 1 trials focus on safety. The experimental drug is given in low doses to a small group (usually less than 100) of healthy volunteers, although in certain cases sufferers of the disease may be used as Phase 1 subjects. Dosing is gradually increased and researchers look to determine how well the drug is tolerated and how it is processed by the human body. This process usually takes about a year. Once an agent is determined to be safe, it can move on to Phase 2 trials.
Phase 2 focuses on effectiveness. The investigational drug is administered to between 100-300 sufferers of the targeted disease. Researchers are looking to determine appropriate dosing, reconfirm safety and evaluate changes in the course of disease. Many drugs fail to make it through Phase 2 trials due to safety problems or side effects (this is usually the first administration to sick subjects). Lack of effectiveness can also derail an agent at this stage.
Phase 3 is the last and most exhaustive of the basic trials. Often thousands of patients are enrolled in Phase 3 trials, which last from 2 to 10 years. Safety is continually monitored and dosing is refined to balance risks and benefits and manufacturing issues are also addressed.
If a Phase 3 trial is successful, the company then files an NDA (new drug application). These filings often run 100,000 pages or more. The FDA has a goal of providing an answer in ten months. There are also several accelerated approval programs. More detailed information on the these alternate programs can be found on the FDA website.
This article has only scratched the surface of the FDA clinical trial process. At each phase, the FDA is intimately involved with trial design and monitoring. For an excellent article on the entire process, please refer to the Wikipedia article here. On to the trials.
Alkermes (ALKS) announced the initiation of a Phase 1/2 study of their compound ALKS 5461 for treatment resistant depression. Treatment resistant depression refers to depressive episodes that are not adequately controlled by standard antidepressant therapy. Studies have shown that 45% of Major Depressive Disorder sufferers did not respond to treatment by a standard antidepressant. Total sales of anti-depressants in 2008 reached $11 billion. Top line results are expected in the second half of 2011.
Chelsea Therapeutics International, Ltd. (CHTP) traded up almost 10% last week on successful completion of its Northera study. Northera treats deficiency of norepinephrine which causes lightheadedness, dizziness, blurred vision and fainting episodes. This study was completed at the request of the FDA, after completion of a Phase 3 trial, to evaluate cardiac safety of Northera, which the FDA previously granted "orphan drug" status. The drug has been approved and marketed in Japan and some surroundig nations (as Droxidopafor different indications. CHTP intends to seek approval for the compound in Q3, 2011. Market size for Northera has been estimated at $200-$300MM. CHTP has just shy of 62 million shares outstanding and a market cap of $325MM.
BiondVax Pharmaceuticals, Ltd. (BNDX-L.TA) announced positive results from its first Phase 2 trial of its flu vaccine, Multimeric-001. According to Ron Babecoff, Biond Vax's CEO,
We have confirmed, in what is to our knowledge the first Phase 2 study of a universal influenza vaccine ever conducted in the world, that Multimeric-001 is not only safe and immunogenic on its own, but is also has the potential to enhance the performance of traditional strain-dependent flue vaccines.
This is potentially significant as it gives the compound two possible endpoints, first for use as an enhancement to tradition annual vaccines and as a universal vaccine against many strains of the flu. Currently, authorities make an educated guess as to which strains will be prevalent in a given year and order production of a vaccine against those strains. Not only is a universal vaccine potentially game changing, but enhancement of existing vaccines also has enormous commercial potential. BNDX is preparing to conduct the next Phase 2 trial in the elderly, a traditionally high risk population for influenza.
Curis, Inc. (CRIS), a Lexington, MA company focuses on targeted small molecule drug candidates for cancer treatment. Curis announced positive data will be presented by its partner, Genentech (now owned by Roche), from a Phase 2 trial evaluating vismodegib in patients with advanced basal cell carcinoma (BCC). BCC is a skin cancer that affects nearly 2 million people annually and is often curable. In a small percentage of patients, and those untreated, the cancer can spread to other parts of the body. Phase 2 results showed that vismodegib shrank tumors, prevented additional growth of tumors or healed externally visible tumors in 75 percents of patients. More detailed information can be found at the Curis website.
These clinical updates are short summaries and should be used as a basis for further research. You should always perform your own due diligence. Many factors can determine whether a particular drug candidate will ever come to market or be profitable and biotech investing should be considered high risk.