InnoMedica’s technology platform is of particular value in oncological applications, since most cancer patients are still treated with chemotherapy. Conventional chemotherapies are highly effective. However, only small amounts of the active agents accumulate in the tumors thereby often causing severe side-effects.
Talidox encapsulates the established chemotherapy Doxorubicin in a liposome. This nanocarrier packaging enables the reduction of side-effects from the chemotherapy circulating in the blood-stream, as well as the accumulation of high concentrations of the active agent directly in the tumor. Talidox-liposomes have a unique design. They are twice as small as conventional liposomes enabling deeper tumor penetration. Due to their reduced size, they furthermore come in larger numbers thereby facilitating cellular uptake. The liposomal nanocarrier also protects the active agent Doxorubicin during circulation in the blood-stream thereby enabling stronger effects in the targeted tumorous tissue while reducing exposure for and damage to healthy organs. This reduction in system-wide exposure lowers somatic stress on the body and accordingly, only comparatively few patients have to abort treatment. The advantageous benefit/side-effect profile of Talidox increases patients’ prospect for successful therapy.
Talidox Sets New Standards in Chemotherapy
In November 2018, Talidox was in use for the treatment of cancer patients in the context of a safety study (Phase I/IIa) conducted by the Swiss Group for Clinical Cancer Research (SAKK) in five Swiss hospitals. The goal of the safety study was to define the optimum dose of Talidox and investigate its toxicity profile and pharmacokinetics. According to the study protocol, 21 patients have been treated with Talidox in a first phase. With the submission of an amendment to Swissmedic in 2020 and the recruitment of nine additional patients, the clinical study was extended to 30 patients. Following a broad initial patient sample, new patients with breast and ovarian cancer were now included into the study at the recommended dose of 40mg/m2, thereby enabling the investigation of the efficacy and tolerability of Talidox in these specific kinds of cancers.
The study was conducted with patients with late stage cancers, who had already received multiple treatments, all of which could not stop tumor growth. To ensure patient safety, the study started with low dosages. The first patients therefore received only marginally therapeutic dosages of Talidox. Study dosages were successively increased, with one patient treated per dose group. Since no dosage limiting toxicity was observed up to the planned dosage of 40 mg/m2, an amendment was submitted for further dosage increase. The remaining study participants were treated with a dosage of 45 mg/m2. After treatment of 21 patients, an optimal benefit/side-effect profile was determined at a dosage of 40 mg/m2 and the treatment dose was defined accordingly. The effective treatment dose is therefore lower than the maximally administrable dose. Particularly pleasing, Talidox is more gentle to the patient than other compounds despite a higher dosage.
The report on the first clinical study of SAKK concludes that treatment with Talidox leads to substantially less pronounced side effects than treatment with conventional chemotherapies. This includes side effects such as heart problems, hair loss, nausea, and vomiting. Talidox’ treatment side effects were furthermore all controllable and reversible.
Furthermore, only one single treatment in the study had to be aborted due to side effects. In contrast, almost 50% of patients in conventional chemotherapy treatment consider discontinuing treatment due to side effects. Finally, it is important to emphasize that all patients in the clinical study already had late stage cancer and were therefore particularly vulnerable to side effects. In sum, the collected data indicate that Talidox can substantially improve the benefit/side-effect profile of chemotherapy.
Study report of the Swiss Group for Clinical Cancer Research (SAKK)
Talidox® adverse event data according to SAKK study report dated January 28, 2021, chapter 4.1.4. treatment-related adverse events, Table 14. All severities of assignment "probably" and "definitely related to Talidox® treatment" at dose levels 40mg/m2 (3 patients) and 45mg/m2 (15 patients) were summed. Comparative data from Swiss www.compendium.ch.
* Ransom (1997): comparable Doxil® dose of 45mg/m2 per 3 weeks.
** Palmar-plantar erythrodysesthesia (PPE, hand-foot syndrome) Severity grade 3 and 4.
Efficacy of Talidox® in late stage patients
Even in patients with late stage cancer with at least three previous lines of treatment, Talidox was able to at least stop tumor growth in 60% of cases. In one in seven patients, tumors were substantially reduced in size or almost completely eliminated. In one patient with metastasizing breast cancer, a 100% reduction of liver metastases could be observed after six cycles (18 weeks) of treatment with Talidox.
CT-scan of the liver metastases before (left) and after treatment in six cycles across 18 weeks (right) with a 100% reduction of the metastases.
Application for Market Approval
Since Talidox uses Doxorubicin, an active ingredient that has already been approved, Swissmedic considers the drug to be a “known substance with innovation”. The use of Doxorubicin is widespread for the treatment of breast, ovarian and lung cancer as well as for the therapy of lymphomas and soft tissue tumors. On the one hand, this categorisation by Swissmedic accelerated the clinical trial and simplifies registration; on the other hand, it reduces the translation risks. Concerning the market approval dossier, this means that existing study results of chemotherapies with free Doxorubicin, liposomal Doxorubicin (Caelyx) and the standard-of-care Paclitaxel could be used as a reference and compared with the preclinical and clinical results of Talidox. The available clinical data demonstrated the tolerability of Talidox and rendered initial evidence of its efficacy. In accordance with preclinical study results, Talidox primises high efficacy as compared against published efficacy and side-effect data of competitor products. In view of the good results from the clinical trial and the categorisation of Talidox as “known substance with innovation”, InnoMedica has decided to submit the dossier for marketing authorisation to Swissmedic in the first half of 2021. In this submission, InnoMedica is seeking approval for the indications of the reference product Caelyx® (metastatic breast cancer, multiple myeloma, ovarian cancer, carposi sarcoma).
For other indications and for use as first-line therapy, additional clinical studies with leading oncologists in Switzerland, Germany and the USA are being prepared in cooperation with SAKK and Prof. Dr. Thürlimann.
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