Pre-clinical studies = When the new drug is tested in test tubes and animals to look for how the drug interacts with a living being.
Phase 0 = A very small study (10-15 people) looking to see how the body processes the drug (pharmacokinetics) and how the body effects the body (pharmacodynamics). This helps us make the decision of going ahead or not with testing of the drug in regular doses.
Phase 1 = These are usually dose finding studies and until recently there were no Phase 0 studies. This phase is focused on safety and tolerability.
Phase 2A = Helps determine how much drug should be used.
Phase 2B = Studies how well the drug works (efficacy).
Phase 3 = The big studies, which (hopefully) lead to a drug's approval by the FDA.
Phase 4 = Postmarketing study after the drug is already FDA approved and being used by patients. Sometimes these are meant to help determine the long term safety of the drug and sometimes they help find a different market for the drug.
Monoclonal Antibodies: mono = one type; clonal =all the same; antibodies = proteins that stick to the surface of certain types of cells.
This medication is already FDA approved for certain types of blood cancers and is being tested in Phase 3 trials for relapsing-remitting multiple sclerosis (RRMS).
In one trial (CARE MS-I) this medication is being compared to Rebif in patients who have never been on a disease modifying drug in the past.
The second trial is still actively recruiting patients (CARE MS-II) who have had MS symptoms for 10 years or less, have had a relapse despite being on a disease modifying agent for 6 months or longer and have had 1 relapse in the last year and 2 in the last 2 years.
Earlier Phase 2 trials indicated that Campath was over 70% better than Rebif (beta interferon 1a under the skin three times a week).
The way Campath is given in the MS phase 3 clinical trials is 12 mg intravenously (IV) daily for 5 days in a row total for the first year and then 3 days in a row total in the second year.
We do not know yet if people will require continued doseing of Campath in year 3 or later or whether 2 cycles are enough.
This is, of course,
a dramatic leap forward because of how infrequently it needs to be given and its dramatic effect, however there are serious potential side effects. In the phase 2 trial, a person starting bruising and bleeding and he didn't go in to see the doctors, and eventually he bled into his brain and died. The reason he was bleeding is that his platelt count was low. Platelets are the part of our blood which is sticky and keeps us from bleeding all the time.
This patient had developed idiopathic thrombocytopenic purpura (ITP) because Campath changes the immune system from attacking the nerves and the covering of the nerves (in MS) to attacking the body in other ways. Therefore, 30% of the patients develop autoimmune thyroid disease and there are other autoimmune diseases, such as Goodpasture;s (the kidneys are attacked) and the ITP. Many people think that it
may be worth it to potentially trade in the autoimmune disease of MS for another type of autoimmune disease. The thinking is that thyroid hormones can be replaced with pills but nerves and their covering (myelin) cannot.
This medication is already FDA approved for certain types of leukemias (blood cancers) and in the past was used only as an injection. It has been studied now in MS to see if the oral form of this medication works for RRMS. The Phase 3 results (CLARITY) show that Cladribine is over 50% more effective than placebo (inactive 'sugar' pill). Cladribine will be given orally once a day for a total of 8 days a year.
There are other trials looking at using Cladribine in combination with standard injectable disease modifying agents (ONWARD) and using Cladribine in patients who have only had one attack of multiple sclerosis (clinically isolated syndrome or CIS).
There are potential safety concerns, such as infections and even cancer (but this is being investigated further).
The most exciting thing about Cladribine is that it is not even taken daily -- it is taken for fived days in a row one month and then again the second month and that is it for the first year. It is taken again for 2 cycles in the second year, and after that we don't know how often it will be taken. This will probably be the first oral medication for MS.
A Phase 3 trial (TRANSFORMS) comparing Fingolimod to Avonex (interferon beta-1a into the muscle once a week) already showed that Fingolimod was over 50% better than Avonex. This is exciting because it is 50% better than another disease modifying agent and not just better than placebo. There are 2 other Phase 3 trials which are going on comparing daily Fingolimod
to placebo for 2 years.
Like all of the newer medications, there are serious potential safety concerns, like infections and cancers (especially skin cancer). Fingolimod also causes a drop in a prson's heart rate, but this is usually stable and does not cause symptoms. There may also be a worsening of
pulmonary function testing, but this, again, does not seem to cause symptoms.
This medication has been tested in a Phase 3 trial (TEMSO) in RRMS patients and is being tested in patients with clinically isolated syndrome (CIS) and in shorter trials
in combination with the standard injectable disease modifying agents.
There appear to be less severe side effects as compared to Cladribine and Fingolimod, but the parent compund, Lelunomide (used in Rheumatoid Arthritis) has serious safety issues.
Laquinimod (also spelled alternatively by some as Laquinomod, including analysts, investor and in the Financial Times by Pharmawire on FT.com):
This medication is being studied in Phase 3 trials comparing it both to placebo and to a standard injectable disease modifying agent. A phase 2 trial suggests that it may have the potential to be both effective and relatively safe.
This medication is being tested in 2 Phase 3 trials -- one comparing it 3 times a day to placebo and the other comparing it to placebo and separately to Copaxone (glatiramer acetate injections under the skin daily).
BG00012 does not seem to suppress the immune system, but rather to modulate it, which suggests that it may not place patients at higher risks for serious side effects, such as infections. It may be difficult to take, however, because it is taken three times a day instead of daily.
This medication is a CGRP (calcitonin gene related peptide) antagonist (inhibitor) being studied in Phase 3 trials for its ability to stop a migraine.
This is a novel way of treating migraines, since the previous pills, called triptans, had an effect on the serotonin receptors and also had
the potential to cause vasoconstriction, making it unavailable to people with heart problems. Telcagepant may not have this problem and so it is being studied in this population.