Roche announced a phase II study with tominersen. Do we know enough?
The recent fase III Generation HD 1 study data discloure from Roche was accompanied by the announcemenet of re-testing the drug in a Fase II study on a subgroup of patients.
A few days ago Roche announced that a Phase II study with tominersen will start soon. Tominersen is the ASO (Oligonucleotide Anti Sense) whose experimental administration was interrupted in March 2021, following the negative evaluation of its effects on patients, by an Independent Evaluation Commission.
We recall that Generation HD1 was a phase III study, extended to a large number of participants, aimed at evaluating the potential therapeutic efficacy of the experimental molecule tominersen. A Phase II study, on the other hand, is aimed above all at identifying the right dosage for a smaller number of participants.
Since the interruption of the drug administration, the company has been analyzing the data collected during the study and has now made some of them known, through an official press release and in a webinar organized by EHDN on 20 January 2022 which, as it was announced, other meetings will follow.
What was communicated
The core of the communication is the following: for a subgroup of patients, made up of younger people (age <48 years); with a lower level of disease severity (measured by a parameter called CAP, <500 in this subgroup) and exposed to a less frequent dosage of tominersen (120 mg every 16 weeks instead of every 8 weeks) tominersen could be favorable. The results, the company itself states in its official statement, are not statistically significant compared to the placebo.
So...what does ‘favorable’ mean?
What was not communicated
- It has not been clarified what exactly the 'advantage' that tominersen would produce, on a clinical and biological level, on patients who are part of the reference subgroup translates into; in science, no statistical significance = no advantage;
- No details were provided on the current health condition of all the other patients involved in the study (about 800 people), who according to the Independent Evaluation Commission not only did not improve after the tominersen administration, but indeed, when they had taken the higher dosage of the drug, they had even gotten worse;
- During Generation HD1, tablets and smartphones were also used to collect vital parameters and daily information from patients: these data were not disclosed.
- Nothing was communicated about the possible biological effects that the reduction of the healthy protein produced on the study participants, nor about the potentially negative ones that the drug itself, as is more likely, could have caused at higher doses.
- These data defined as “favorable” are the result of a completely arbitrary division into sub-categories of patients.
During the webinar organized by EHDN on January 20, 2022, many questions were asked to Roche speakers and panelists, which were answered at the end. The most difficult and thorny questions, however, those aimed at better understanding, deeper understanding the meaning of the data presented, remained unanswered.
Our unpleasant impression was that it was chosen not to give space to a critical confrontation (the only possible one, in our opinion, in the interest of patients), but that organizers chose to remain at a superficial level of information.
A situation like this, that is the possibility that a drug tested without success in a phase III could be tested again in a phase II on a more limited population, does not happen every day, gives hope to thousands of families: therefore, transparency is a must, for ethical reasons, as well as for scientific reasons.
It is not acceptable, in our opinion, that patients have not received details on the 'danger' profile of the drug administered at the highest dosages. It is not acceptable not to have received a reason why an effect is considered beneficial, in the absence of statistical significance. It is not reassuring to have witnessed a debate where everyone agreed with everyone.
LIRH Foundation believes in research.
The possibility that an experimental drug may have a 'second chance' is a positive fact, in principle. In practice, however, especially if we are talking about a rare and still untreatable disease such as Huntington's, with all the enormous and multiple problems it brings with it, we cannot rejoice in principle.
We need facts, evidence, we need something more. Above all, because - as far as we are concern - other ongoing trials offer a more convincing background of information.
We invite patients, researchers and the media to critically evaluate the information that circulates, remembering that even those that do not circulate have a weight.
We invite Roche to raise the profile of transparency and ethics towards the Huntington community (already several times, in past years and for different experiences, burned by their absence), for everything related to the tominersen study.