“We are particularly encouraged by the sustained benefit, with patients remaining on treatment much longer than expected. The median time to progression of more than 10 months is significantly longer than previously achieved in second-line treatment with, among others, Lenvima monotherapy or other treatment options,” says Medivir’s CEO. Jens Lindberg.
Medivir develops fostrox for the treatment of primary liver cancer, hepatocellular carcinoma (HCC) – the most common type of liver cancer and the fastest growing cancer in the U.S. Approximately 660 patients are diagnosed with primary liver cancer globally each year.
Liver cancer with high mortality and few treatment options
HCC is a very difficult-to-treat cancer and the third leading cause of cancer-related death worldwide. Existing treatments for HCC can prolong patients' lives, but the treatment effect is often insufficient, which means that mortality remains high. The current five-year survival rate is less than 20 percent.
The standard first-line therapy is immunotherapy and current treatment guidelines recommend the combination therapy Tecentriq/Avastin. For patients who do not respond to first-line treatment, there are no approved second-line drugs. Recently, at the American oncology conference ASCO, new data were presented on second-line treatment with an immunotherapy, Keytruda, in combination with a drug called Stivarga. Data that showed a limited effect, including a median progression-free survival of only 2.8 months after Tecentriq/Avastin in first line. Results that further confirm that HCC is a challenging disease to treat with a large unmet medical need.
Medivir gives hope to difficult-to-treat patient population
Medivir's drug candidate fostrox, in combination with the tyrosine kinase inhibitor Lenvima, offers hope to patients who are left without treatment options after they have stopped responding to immunotherapy. The goal is for the combination therapy to become the first, approved treatment option after first-line treatment.
Fostrox is a liver-targeted inhibitor of cancer cell DNA replication, which differentiates it from existing first-line HCC treatments. The candidate delivers its cell-killing agent selectively to tumor cells in the liver while minimizing damage to healthy cells.
The safety and tolerability of Fostrox is currently being evaluated in a fully recruited Phase Ib/IIa study in combination with Lenvima. The next step will be to initiate a global randomized Phase IIb study in early 2025 where the combination treatment will be evaluated compared to Lenvima alone in second-line HCC. Medivir has established a collaboration with a global CRO (Contract Research Organization) for the upcoming Phase IIb study. In addition, Fostrox has orphan drug status for the treatment of HCC in both the US and Europe, which facilitates development.
New compelling data presented at ESMO GI
New data from the phase Ib/IIa study show that the combination treatment Fostrox + Lenvima provides greatly improved outcomes for patients with primary liver cancer. Today, Dr. Hong Jae Chon the new results from the study in a poster presentation at ESMO GI (European Society of Medical Oncology, Gastrointestinal Cancers) Cancer Congress in Munich, Germany. Dr. Hong Jae Chon is a professor at CHA Bundang Hospital in Korea and also an investigator in the study.
The new results show that fostrox + Lenvima achieved an Overall Response Rate (ORR) of 24 percent and an estimated median time to progression (TTP) of 10,8 months. This compares to the current prognosis for many second-line HCC patients, where only 5–10 percent of patients respond to current standard of care and a typical TTP is 3–4 months.
“These data for fostrox + Lenvima show very promising clinical benefit for patients. They indicate that when fostrox is added to Lenvima, the effect is better than expected with Lenvima monotherapy. I look forward to further exploring the effect of fostrox plus Lenvima in a randomized, controlled trial,” says Dr. Hong Jae Chon.
Does not affect normal liver function
According to Dr. Dr. Hong Jae Chon, there is a need for new treatments that do not impair liver function and that have different mechanisms of action compared to first-line treatment. Most HCC patients have impaired liver function due to liver cirrhosis and therefore it is important that the treatment not only treats the tumor, but also protects against deterioration of liver function. Biopsies from Medivir's study with fostrox confirm selective DNA damage to tumor cells, without any impact on normal liver function.
The fact that normal liver function is not affected supports previous safety and tolerability data, where few patients have discontinued treatment due to side effects and the need for dose reduction has been lower than expected. According to the new results from the study, approximately 25 percent of patients remain on treatment and the patient who had the longest benefit is still being treated after 22 months, with a sustained partial response.
Comments from the CEO
BioStock sought Medivir's CEO Jens Lindberg for a comment.
Jens, what is the most important thing about the new results and how do they relate to previous updates?
– Two parts, firstly that the patients remain on treatment and benefit clearly longer than expected given what previous studies in second-line HCC have shown. The median time to progression with fostrox + Lenvima in this study is significantly longer than what has previously been shown in second-line treatment. But it is also extra important for this patient group that normal liver function is not negatively affected, which is why it is very encouraging that with these new results we once again show a selective, cell-killing effect on tumor cells and that the normal function of the liver is not affected by fostrox's liver-targeted anti-tumor effect.
Why are the new results promising for the difficult-to-treat patient group with HCC?
– In previous studies, the treatment effect for these patients has amounted to 3-4 months before the tumor started to grow again. The results we present today indicate the potential for a significant increase in this time for the combination fostrox + Lenvima. Perhaps above all, an opportunity for patients to get a truly long-lasting effect like the patient who responded to the treatment and still benefits from the treatment after 22 months. It is also important that the increase that today's results indicate is clinically relevant, which is of utmost importance for future interactions with regulatory authorities.
Could you tell us a little more about the advantages of your combination treatment compared to other treatment options?
– When a patient no longer responds to first-line treatment, it is often because the tumor cells have developed resistance to the current treatment, making it especially important to change the mechanism of action in the next line of treatment. For example, a study recently presented at the American oncology congress ASCO showed that switching to a different immunotherapy combination in the second line did not provide any additional effect.
– Fostrox and Lenvima have two different mechanisms of action that complement each other to combat tumor cells in the liver as well as metastases outside the liver. In addition, this combination has also shown additive effect in non-clinical studies. These are factors that support why this particular combination could have such a significant effect in this patient population as the data presented today indicates.
Finally, how has your new study data been received at the ESMO GI Congress?
– With great interest. The lasting clinical benefit stands out compared to what has previously been shown in second-line treatment. In addition, fostrox does not affect normal liver function, which is also a clear advantage for this patient population. The lack of approved drugs in second-line HCC, together with the lack of effect presented at ASCO when switching to another immunotherapy combination in second-line, has also contributed to increased interest in this unique treatment combination for liver cancer.