“The post “Is alemtuzumab too risky?” has, not surprisingly, generated a lot of discussion about the FDA’s current position on alemtuzumab. Why has the FDA taken this position on alemtuzumab, and why did it reject cladribine? Both these drugs are induction agents, i.e. given as short courses, with the potential for long-term remission and in hopefully in some cases the possibility of a cure.”
“I am in Canada at the moment on a lecture tour and gave a talk last nigh to make the case for induction therapies. I have uploaded my slides below. The case I am making is for MSer choice. I see no reason why a well informed person with the disease cannot make a rational decision about risks and potential benefits of the various treatment themselves? Why should regulators act as gate keepers? If the FDA does not license alemtuzumab for treating MS it will be the second induction therapy they have turned down. Not having the option of an induction therapy will limit treatment options for MSers in the US. In slide 77 from the deck below I try and compare, and contrast, the differences between maintenance and induction therapy strategies.”
“The main differences is that induction therapies are irreversible, highly efficacious and are the only option that offers a potential for long-term remission and possibly a cure. The latter is based on the premise that MS is an autoimmune disease and that by rebooting the immune system you may get rid of the MS autoimmune response. For woman with MS induction therapies offer great advantages for having children; you can get on top of your MS disease activity and you can fall pregnant with the knowledge that no drug is in your body that is potentially teratogenic. Induction therapies allows you to put yours and your unborn child’s interests on a par. I don’t think this latter attribute of induction therapies can be under estimated. There is one proviso in relation to alemtuzumab that needs to pointed out; auto-antibody mediated autoimmune diseases that may develop after alemtuzumab treatment may affect pregnancy. For example, antibodies that stimulate the thyroid gland may cross-over the placenta to affect the developing baby’s thyroid gland causing foetal hyperthyroidism. Although this will be a rare complication of alemtuzumab treatment it is something that needs to be considered. Fortunately, foetal hyperthyroidism is treatable.”
“I am still raw about the EMA’s and FDA’s decision on cladribine. Both regulatory agencies were concerned about the long-term cancer risk of cladribine-treated MSers. How do you resolve this?The only way would have been to given cladribine a conditional license with the requirement from the company who developed the drug to comeback with post-marketing surveillance to see what the long-term cancer risk was. Doing another phase 3 study would not have provided the information; long-term cancer risks can only come from long-term surveillance studies. The great tragedy is that Merck-Serono pulled the plug on their cladribine development programme before the results of their CIS, or clinically isolated syndrome, study were in.
These results were stunning and the best CIS results to date. Would it not be a tragedy if a large proportion of those CISers treated with cladribine, who have flat-lined, never develop MS in the future? Imagine if we have thrown away the the chance of a potential MS cure for some CISers? The same may happen to alemtuzumab in the US. If you are an MSer who has received alemtuzumab and have done well you need to stand-up and be counted. Other MSers deserve the chance of saying yes or no to an induction therapy. I agree there are risks to these treatments, some of which are potentially life-threatening, but they are much lower than the risks associated with bone marrow transplantation, the most extreme form of induction therapy. Several countries are still running MS bone marrow transplantation programmes. Why does the EMA and FDA not close these programmes down?”