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Merck Wins Another FDA Approval for Blockbuster Keytruda
Merck & Co arrived just two months after GSK celebrated a positive phase III result with its checkpoint inhibitor Jemperli as a first-line therapy for endometrial cancer. Keytruda (pembrolizumab) from Merck improved progression-free survival (PFS) versus chemotherapy alone in patients with stage 3 to 4 or recurrent endometrial carcinoma, regardless of mismatch repair status, in the late-stage NRG-GY018 trial.
The findings follow GSK’s announcement that Jemperli (dostarlimab) plus chemo performed well in the RUBY trial in patients with primary advanced or recurrent endometrial cancer, becoming the first immunotherapy to improve PFS when used as first-line treatment in patients with and without mismatch repair mutations.
Merck has stated that it will now consider regulatory filings for Keytruda based on the findings of the NRG-GY018 study, which was conducted by the National Cancer Institute (NCI) in the United States. Both Keytruda and Jemperli are already approved as monotherapies in the second- or later-line treatment of endometrial cancer, but approval in the first-line setting would open up a larger eligible patient population.
GSK’s drug was approved by the FDA in August 2021 for recurrent or advanced endometrial cancer with mismatch repair deficient (dMMR) mutations, and the company announced in December that Jemperli would be approved for first-line use in the first half of 2023. Meanwhile, in March 2022, the FDA approved Keytruda in advanced endometrial carcinoma with microsatellite instability-high (MSI-H) or dMMR, as well as in a combination regimen with Eisai’s Lenvima (lenvatinib) in previously treated endometrial cancer without dMMR mutations.
Merck would benefit from approval in first-line endometrial cancer, adding to a long list of indications for Keytruda, which has made it the undisputed market leader among checkpoint inhibitors, with sales of more than $20 billion last year.
Sanofi Puts Brakes on Phase III Trials of Myasthenia Gravis Candidate tolebrutinib
Sanofi is still developing tolebrutinib, an oral BTK inhibitor, for multiple sclerosis but has decided to abandon efforts to develop the drug for the neuromuscular disorder myasthenia gravis. Sanofi announced in its fourth-quarter results update that it had discontinued the phase III URSA trial of tolebrutinib in patients with moderate-to-severe myasthenia gravis, but stressed that the decision was made for commercial reasons due to the “emerging competitive treatment landscape” for the disease.
The FDA placed a partial clinical hold on tolebrutinib phase III trials in MS and myasthenia gravis last year after cases of drug-induced liver injury were discovered, and recruitment for new studies was halted. Sanofi later stated that all of the cases were seen in patients who had predisposing conditions that made them vulnerable to this type of reaction and that the protocol for the studies had been revised to exclude them, allowing recruitment to resume.
Myasthenia gravis is a severe, rare, chronic neuromuscular autoimmune disease that causes debilitating and potentially fatal muscle weakness. In Europe, there are approximately 60K to 120K people living with the condition, compared to approximately a million with MS, making it much less common.
Tolebrutinib is still being studied in two phase III studies in relapsing MS (GEMINI I and II) as well as non-relapsing MS (HERCULES and PERSEUS), with results expected by the end of 2023 or the beginning of next year, ahead of filings later in 2024.
Sanofi confirmed on Friday that it has completed recruitment in HERCULES, its US study in non-relapsing, secondary progressive MS, where there is the greatest need for new therapies, and that the ex-US PERSEUS trial in primary progressive MS is still enrolling patients.
Sanofi’s decision to discontinue the development of the drug in myasthenia gravis may be influenced by the changing landscape of disease therapies, such as the approval of Argenx’s neonatal FC receptor (FcRn) antibody Vyvgart (efgartigimod alfa).
FDA Approves GlaxoSmithKline’s Jesduvroq for Anemia
The FDA has approved GlaxoSmithKline’s Jesduvroq (daprodustat), the first oral treatment for anemia caused by chronic kidney disease (CKD) in adults on dialysis for at least four months. Other FDA-approved treatments for anemia (low red blood cell count) caused by CKD in adults on dialysis are injected into the blood or administered through the skin. Jesduvroq is not approved for patients who are not on dialysis because its safety in this patient population has not been established.
Over 500K adults in the United States have CKD and require dialysis, a treatment that filters the blood and removes excess fluid. Jesduvroq, an oral treatment from GSK, raises erythropoietin levels. Its efficacy was demonstrated in a randomized trial of 2,964 dialysis patients. Adults in the study were given either Jesduvroq or recombinant human erythropoietin by injection (a standard of care treatment for patients with anemia due to CKD).
Jesduvroq, like recombinant human erythropoietin, was found to raise and maintain hemoglobin (the protein in red blood cells that carries oxygen and is a common measure of anemia) within the target range of 10 to 11 g/dl. Jesduvroq carries a label that warns of an increased risk of thrombotic vascular (blood clotting) events such as death, heart attack, stroke, and blood clots in the lungs, legs, or dialysis access site. Other Jesduvroq warnings and precautions include the risk of hospitalization for heart failure, worsening of pre-existing blood pressure issues, and stomach erosions and gastrointestinal bleeding.
The Scottish Medicines Consortium (SMC) approved Bayer’s CKD drug, Kerendia (finerenone), for the treatment of adults with CKD associated with type 2 diabetes (T2D) in NHS Scotland in December 2022. AstraZeneca also expanded its cardiorenal pipeline earlier this month with the $1.3 billion acquisition of CinCor Pharma, with the $26-per-share upfront deal focusing on baxdrostat (CIN-107), an aldosterone synthase inhibitor (ASI) in clinical testing for treatment-resistant hypertension and chronic kidney disease.
Hinova Receives FDA Proceed Authorization for its IND Application for HP518 to Treat Prostate Cancer
On Feb. 7, 2023, Hinova Pharmaceuticals Inc. announced that the US FDA had cleared the company’s investigational new drug application (IND) for its innovative drug HP518, an oral chimeric degrader targeting the androgen receptor (AR) for the treatment of metastatic castration-resistant prostate cancer (mCRPC). At present, the HP518 is in Phase I clinical trials in Australia. The open-label study approved by FDA will assess the safety, pharmacokinetics, and antitumor activity of HP518. In preclinical studies, HP518 showed excellent selectivity and degradation activity against wild-type AR and some specific AR mutants that are resistant to enzalutamide. HP518 also demonstrated excellent antitumor efficacy in xenograft mouse models.
Upon receiving the FDA’s IND clearance, Yuanwei Chen, Ph.D., President and CEO of Hinova stated that “the available study results of HP518 strengthen our confidence that HP518 is a potentially new treatment for drug-resistant prostate cancer. We are making full efforts to advance the clinical study, hoping HP518 will provide more clinical benefits to patients worldwide in the future.”
As per DelveInsight’s assessment, the total prevalent cases of Prostate Cancer in the 7MM were observed to be 6,985,000+ in 2018, which is expected to increase in the coming years. Among the 7MM, the highest number of prevalent cases was observed in the United States, with 3,266,000+ cases in 2018. On the other hand, in EU-5 countries, the highest number of diagnosed prevalent cases of prostate cancer were found in Germany, with 393,000+ cases in 2020, followed by France and Italy.
There are several treatment options available to treat this condition; however, there are several unmet needs in the therapeutics segment. The approval and the launch of emerging potential therapies like HP518, among others, are anticipated to transform the treatment scenario in the coming years. HP518 has been discovered and developed through Hinova’s targeted protein degradation drug discovery platform. It has the potential to overcome the drug resistance of prostate cancer that is due to some specific AR mutations. AR is a validated therapeutic target to treat prostate cancer. During the treatment of prostate cancer, drug resistance becomes inevitable due to multiple mechanisms, including AR amplification or mutations, etc.
Endogena Therapeutics Receives US FDA Fast Track Designation for its Drugs, EA-2353 to Treat Retinitis Pigmentosa
On Feb. 06, 2023, Endogena Therapeutics Inc. announced that the US FDA had designated the investigation of EA-2353 for treating Retinitis Pigmentosa (RP) as a Fast Track development program. EA-2353 takes a novel, small-molecule approach and selectively activates endogenous retinal stem and progenitor cells, which differentiate into photoreceptors and can potentially preserve or restore visual function. This gene-independent treatment approach has significant advantages in Retinitis Pigmentosa, which has multiple genetic causes.
On receiving US FDA Fast Track Designation for EA-2353, Matthias Steger, Ph.D., MBA, CEO of Endogena, said: “This acknowledgment by the FDA of the potential of EA-2353 for Retinitis Pigmentosa gives hope for patients living with this devastating degenerative disease. It is a significant milestone for our company, and our investors, and gives recognition to our dedicated team at Endogena, who has been working for the past six years to reach this point.”
Endogena Therapeutics is currently conducting a phase 1/2a dose-escalation study to examine the safety, tolerability, and preliminary efficacy of EA-2353 administered by intravitreal injection in patients with Retinitis Pigmentosa. As per the update, about 14 patients with Retinitis Pigmentosa due to any pathologic genetic mutation are being recruited across up to six sites in the USA, and the first patient was dosed in July 2022. The Fast Track designation will enable Endogena Therapeutics to have more frequent communications with the US FDA on the development of EA-2353 and allow a more rapid regulatory review of the future new drug application. Earlier in May 2021, EA-2353 was granted orphan drug designation by the US FDA.
Retinitis Pigmentosa is a serious and debilitating condition and a leading cause of inherited blindness, affecting around 1.5 million people worldwide. As per DelveInsight’s assessment, in 2021, the diagnosed prevalent population of Retinitis Pigmentosa in 7MM was 259,000+. The diagnosed prevalence of Retinitis Pigmentosa in the United States was 111,000+. Moreover, among the European 5 countries, Germany had the highest diagnosed prevalent population of Retinitis Pigmentosa, with 30,000+ cases, followed by France and the United Kingdom in 2021. The approval of therapies, such as EA-2353, anticipates a better Retinitis Pigmentosa treatment scenario in the coming.
Amylyx Pharmaceuticals Completes the Enrollment in Global Phase 3 PHOENIX Trial of AMX0035 in ALS
Amylyx Pharmaceuticals has updated that it has completed the enrollment in PHOENIX, a global, 48-week, randomized, placebo-controlled Phase 3 clinical trial of AMX0035 (sodium phenylbutyrate and taurursodiol [also known as ursodoxicoltaurine]) in patients with Amyotrophic Lateral Sclerosis (ALS). The study is expected to enroll 664 participants living with Amyotrophic Lateral Sclerosis. Moreover, Amylyx anticipates topline results in 2024.
The design of PHOENIX was informed by the results of the Phase 2 CENTAUR clinical trial of AMX0035, which demonstrated a statistically significant benefit in function, as well as an observed benefit on survival in a longer-term post hoc analysis. Overall, reported rates of adverse events and discontinuations in CENTAUR were similar between AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2%) in the AMX0035 group.
Leonard H. van den Berg, MD, Ph.D., Professor of Neurology at UMC Utrecht in the Netherlands and Chairman of the Treatment Research Initiative to Cure ALS (TRICALS), has stated that “the Phase 3 PHOENIX trial was an excellent collaboration between European and United States Centers for excellence in Amyotrophic Lateral Sclerosis research and care. We anticipate that PHOENIX will help us generate further data about the safety and efficacy of AMX0035”.
“We are grateful for the people living with Amyotrophic Lateral Sclerosis and their families who are participating in PHOENIX and the dedication of the study investigators. We remain committed to continuing research and exploring the full potential of AMX0035 as part of our mission to one day end the suffering caused by Amyotrophic Lateral Sclerosis and other neurodegenerative diseases” – Joshua Cohen and Justin Klee, Co-CEOs of Amylyx.
AMX0035 is approved to treat Amyotrophic Lateral Sclerosis in the U.S. as RELYVRIO™ (sodium phenylbutyrate and taurursodiol) and approved with conditions in Canada as ALBRIOZA™ (sodium phenylbutyrate and ursodoxicoltaurine). Moreover, the European Medicines Agency (EMA) is reviewing the Company’s Marketing Authorisation Application for AMX0035 for the treatment of Amyotrophic Lateral Sclerosis in Europe. Furthermore, AMX0035 is being explored for the potential treatment of other neurodegenerative diseases.
As per DelveInsight, in the US, there were approximately 25,817 diagnosed prevalent cases of Amyotrophic Lateral Sclerosis in 2021. Moreover, among the EU-4 and the United Kingdom countries in 2021, Germany had the highest diagnosed prevalent cases of Amyotrophic Lateral Sclerosis, with 5,300+ cases, followed by the UK (4,500+) and Italy (4,400+). In contrast, Spain had the lowest cases (3,200+) in 2021.