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Medivir presents promising results in difficult-to-treat patient population


Medivir presents promising results in difficult-to-treat patient population

27 June, 2024

Medivir today presents new clinical data from its phase Ib/IIa study at ESMO GI in Munich. The company’s candidate fostrox shows strongly improved results in combination with Lenvima for patients with advanced primary liver cancer, a difficult-to-treat patient group that currently lacks approved treatment options in the second line.

– We are particularly encouraged by the durable benefit, with patients remaining on treatment for much longer than expected. More than 10 months median time to progression is significantly longer than previously achieved with second-line treatment with Lenvima monotherapy or other treatment options, says Medivir’s CEO Jens Lindberg.

Medivir is developing 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 US. Approximately 660,000 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 form of cancer and the third most common cause of cancer-related deaths in the world. Existing treatments for HCC can prolong patients’ lives, but the treatment effect is often insufficient, and the mortality is high. The current five-year survival rate is less than 20 percent.

First line treatment is immunotherapy, and current guidelines recommend a combination of Tecentriq and 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 for second-line treatment with an immunotherapy, Keytruda, in combination with a drug called Stivarga. The data showed limited efficacy, including a median progression-free survival of only 2.8 months after Tecentriq/Avastin in the 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, gives hope to patients who are left without treatment options after they have stopped responding to immunotherapy. The goal is for the combination therapy to be the first approved treatment option after first-line treatment.

Fostrox is a liver-directed inhibitor of cancer cells’ DNA replication, which makes it different from existing HCC treatments. The candidate delivers its cell-killing substance selectively to the tumour cells in the liver, while minimising damage to healthy cells.

The safety and tolerability of fostrox are currently being evaluated in a fully recruited phase Ib/IIa study in combination with Lenvima. The next step will be to initiate a global randomised phase IIb study in early 2025, where the combination therapy will be evaluated compared to Lenvima alone in second-line HCC.

Medivir has established a collaboration with a global Contract Research Organization (CRO) for the upcoming phase IIb study. In addition, fostrox has orphan drug designation for the treatment of HCC in both the US and Europe, which facilitates development.

New convincing data presented at ESMO GI

New data from the phase Ib/IIa study show that the combination therapy fostrox + Lenvima provides greatly improved outcomes for patients with primary liver cancer. Today, Dr. Hong Jae Chon presents the new results from the study in a poster presentation at the 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 can be compared to the current prognosis for many HCC patients in the second line, where only 5–10 percent of patients respond to current standard treatment and a typical TTP is 3–4 months.

–  These data for fostrox + Lenvima show highly encouraging clinical benefits for patients. They indicate that when adding fostrox to Lenvima, efficacy is better than expected from Lenvima alone. I look forward to further explore the efficacy of fostrox plus Lenvima in a randomized, controlled trial, said Dr. Hong Jae Chon.

Does not affect normal liver function

According to 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, so it is important that the treatment not only treats the tumour, but also protects against deterioration of liver function. Biopsies from Medivir’s fostrox study confirm selective DNA damage to tumour cells, with no impact on normal liver function.

The lack of impact on normal liver function supports the previous safety and tolerability data, with few patients discontinuing treatment due to adverse events and the need for dose reduction being lower than expected. According to the new results from the study, about 25 per cent of patients remain on treatment, and the patient who has benefited the longest is still on treatment after 22 months, with a sustained partial response.

CEO comments

Jens Lindberg, CEO of Medivir

BioStock reached out to 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 much 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 previously shown in second-line treatment.

– But it is also extra important for this patient group that the normal liver function is not adversely affected, which is why it is very encouraging that, with these new results, we once again show a selective, cell-killing effect on tumour cells and that the liver’s normal function is not affected by the liver-directed anti-tumour effect.

Why are the new results hopeful for the difficult-to-treat patient group with HCC?

– In previous studies, the treatment effect for these patients has been 3 – 4 months, before the tumour has started to grow again. The results we present today indicate the potential for the combination fostrox + Lenvima to increase this time significantly. In addition, it provides an opportunity for patients to have a really long-lasting effect, like the patient who has responded and still benefits from the treatment after 22 months.

– It is also important that the increase indicated by today’s results is clinically relevant, which is of utmost importance for future interactions with regulatory authorities.

Could you tell us a little more about the benefits of your combination therapy compared to other treatment options?

– When a patient no longer responds to first-line treatment, it is often because the tumour cells have developed resistance to ongoing treatment, in which case it is of extra importance 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 another immunotherapy combination in the second line did not have any additional effect.

– Fostrox and Lenvima have two different mechanisms of action, that complement each other to fight tumour 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 indicate.

Finally, how has your new study data been received at the ESMO GI congress?

– With great interest. The durable, clinical benefit stands out compared with what has been shown previously in second line but the lack of impact on normal liver functions is also a clear positive in this patient population. The lack of approved drugs for second-line HCC, in combination with the absence of effect that was shown at ASCO when switching to another immunotherapy combination in second line, has also contributed to an increased interest in this unique treatment combination for liver cancer.

The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.

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