Primary liver cancer, of which hepatocellular carcinoma (HCC) is the most common type, ranks as the third leading cause of cancer-related deaths globally. Although there are treatments that can prolong the lives of patients with HCC, not all patients respond to these treatments, resulting in a continued high mortality rate.
Medivir's approach
Current guidelines recommend Tecentriq/Avastin as first-line treatment, but for those who do not respond to this treatment, the outlook is bleak. This highlights the critical need for second-line treatment options, and this is where the pharmaceutical company Medivir sees its drug candidate fostrox as having the potential to make a big difference for HCC patients. Fostroxacitabine bralpamide (fostrox), a chemotherapy prodrug designed to target the liver, achieves a remarkable 100-fold higher concentration in the liver compared to systemic chemotherapy.
Fostrox has been developed to achieve a targeted antitumor effect by optimizing the concentration of the active substance in the liver, while keeping the concentration in the rest of the body lower to minimize potential side effects. Fostrox's mechanism of action, inhibition of cancer cell DNA replication and induction of DNA damage and cell death, is well established in cancer therapy.
In addition, this prodrug category has the ability to effectively deliver the active substance to the liver, as has been demonstrated in antiviral drugs for hepatitis C. Fostrox has received orphan drug (ODD) status in both the US and Europe for the treatment of HCC.
Strong interim data
Fostrox is currently undergoing a Phase Ib/IIa, open-label, multicenter, dose escalation and dose expansion study. During the last quarter, all patients have completed at least two treatment cycles and interim data have shown early and sustained improved clinical benefit as well as a good safety and tolerability profile when fostrox is combined with Lenvima.
Notably, a complete tumor response, a rarity in this patient group, was observed in one patient. During a webcast last week, more mature interim data from 18 of 21 patients with at least 12 weeks of follow-up were presented with a 22 percent Overall Response Rate (ORR) and a prolonged median time to progression of approximately five months, which is clearly higher than historical comparisons in second-line HCC. In particular, the data show that the combination treatment improves clinical efficacy while maintaining the tolerability profile compared to data when Lenvima is given as monotherapy in second-line HCC.
Has formed a scientific council
In August, as clinical activities accelerated for the company, Medivir announced the formation of a scientific council to help plan for the next phase of development. All members are internationally recognized experts in liver cancer.
Dr Richard Finn is a professor of medicine at Geffen School of Medicine, Ph.D Arndt Vogel is a senior consultant and professor at Hannover Medical SchoolIn addition, we have from Dr. Jeong Heo, professor of internal medicine at Pusan National University School of Medicine, and Dr. Maria Reig, head of BCLC and Liver Oncology Unit at Hospital Clinic of Barcelona in Spain. Last but not least, Dr. Jeff Evans, professor of translational cancer research at the School of Cancer Sciences, University of GlasgowThe last trio are also investigators in the clinical development program for fostrox.
Comments from the CEO
To learn more about the new promising results and to get his perspective on the potential future of fostrox in the primary treatment of liver cancer, BioStock contacted Medivir's CEO Jens Lindberg.
Jens, what is the significance of the new data regarding Fostrox in combination with Lenvima?
– As there are currently no approved second-line HCC treatments after Tecentriq/Avastin, the results are very encouraging for patients. The lack of treatment options means that current treatment guidelines recommend patients participate in clinical trials. However, these data indicate that Fostrox/Lenvima has the potential to transform second-line treatment, a market that by 2028 will be worth approximately USD 2,5 billion annually.
How did the industry react to the latest interim data?
– Several industry analysts have revised their target prices for Medivir since the release of the new interim clinical data report last week, including Erik Penser Bank and Redeye. While we do not typically comment on the current share price, it is worth noting that HC Wainwright & Co Equity Research was impressed by our Phase Ib/IIa data and reiterated their Buy recommendation with a target price of SEK 50 based on the NPV model, compared to the current share price which is currently around SEK 7-8.
What is the potential for obtaining accelerated approval of Fostrox and what measures are being taken to achieve this?
– Accelerated approvals are intended for serious diseases, often with orphan drug status, with a high medical need. HCC is one such disease, especially in the context of second-line treatment. Our plan is therefore to design the next study in such a way that if we can replicate the benefit for patients that we see in the ongoing study, we see a path towards accelerated approval in 2027. A key factor is to ensure that the study is of an appropriate size so that there are enough patients in the safety database. Another key factor is that it is a randomized study compared to Lenvima with a regulatory approved endpoint. With the currently planned design, we are taking steps to meet both of these requirements.
What role does Medivir's scientific advisory board of liver cancer experts play in shaping the clinical development plan for Fostrox?
“They play a critical role as we break new ground in second-line HCC. No treatments have been approved or evaluated for regulatory approval in this patient setting since Tecentriq/Avastin. The members of the council are some of the world’s most respected experts in HCC and have extensive experience designing and conducting the clinical trials behind regulatory approvals in first-line HCC, and can therefore provide important guidance as we finalize our plans for the next phase.”
Given the promising interim results, can you share your thoughts on when Fostrox might reach the market?
– Our goal is now to move forward as quickly as possible, which means initiating the next phase IIb study with registration intent in 2024 to enable accelerated approval as early as 2027.
What does orphan drug status mean for Fostrox, and how does it affect the regulatory approval process?
– As previously mentioned, most of the accelerated approvals in oncology have been for orphan drugs. Since HCC is an orphan disease and fostrox already has orphan drug status, we believe this will be one of the most important contributing factors to fostrox receiving accelerated approval.
Several of your other projects are already out-licensed. What progress have you seen with the partnering programs in 2023 and what key milestones do you expect going forward?
– We have seen great progress in all programs and birinapant is the one that has advanced the most in the dose escalation phase in combination with IGM-8444 and the ability to combine has been very encouraging so far without DLT. Two of the other programs, TNG348 with Tango Therapeutics and MET-X with Infex Therapeutics, are both scheduled to enter Phase I studies in the first half of 2024.
Finally, what are you most excited about regarding Medivir's potential future?
– The data we are seeing with Fostrox + Lenvima is very promising. The strength of the data has opened up the possibility of accelerated approval as early as 2027. The opportunity to develop a breakthrough drug for patients where no other drugs are approved is a once-in-a-lifetime opportunity.