Ipsen to Buy Biopharmaceutical Company Epizyme for USD 247 Million

The restructuring of French manufacturer Ipsen has progressed with a takeover agreement for US competitor Epizyme and its cancer drug Tazverik in a deal for slightly less than USD 250 million. Ipsen is proposing USD 1.45 per share for Epizyme, valuing the US company at roughly USD 247 million, and is also promising a contingent value right (CVR) payment of up to USD 1 per share if Tazverik (tazemetostat) meets specific development and sales milestones. The acquisition comes shortly after Ipsen revealed plans to sell its consumer health business for roughly €350 million, leaving the company as a pure-play prescription pharma focused on cancer, rare disorders, and the brain.

It will also generate near-term revenue as Ipsen faces regulatory delays for palovarotene, an ultra-rare disease therapy acquired in 2019 through its USD 1.3 billion acquisition of Clementia Pharma, and sales erosion for top-selling acromegaly and neuroendocrine tumor therapy Somatuline (lanreotide). 

Tazverik is a first-in-class EZH2a inhibitor that the FDA approved in 2020 as a third-line or later treatment for individuals with relapsed or refractory follicular lymphoma (FL) with an EZH2 mutation. It is also approved for patients aged 16 and older with metastatic or locally advanced epithelioid sarcoma who are not candidates for total surgical excision and is in phase III testing as second-line therapy for FL in combination with rituximab and lenalidomide.

The CVR offer from Ipsen comprises USD 0.30 per share if Tazverik achieves USD 250 million in annual sales in four consecutive quarters before the end of 2026 and USD 0.70 if the drug is approved for second-line FL inflation by January 1, 2028. Epizyme’s stock is currently trading at roughly USD 0.95, significantly below its 52-week high of USD 9.86.

BioMarin Gene Therapy for Hemophilia on Course for EU Approval

The European Medicines Agency has recommended that BioMarin’s Roctavian, also known as valoctocogene roxaparvovec, be granted conditional approval to treat patients with severe hemophilia A who do not have factor VIII inhibitors. Patients should also be tested negative for antibodies to adeno-associated virus serotype 5, which is used as the vector for gene therapy. 

The CHMP based its positive opinion on the totality of data from the valoctocogene roxaparvovec clinical development program, the most extensively studied gene therapy for hemophilia A, including two-year results from the global GENEr8-1 Phase III study, supported by five and four years of follow-up from the 6e13 vg/kg and 4e13 vg/kg dose cohorts in the ongoing Phase 1/2 dose-escalation study, respectively. BioMarin has committed to continuing to collaborate with the larger community to track the long-term impacts of treatment.

The favorable assessment paves the way for Roctavian to receive official European Commission approval in the third quarter. The favorable opinion comes two years after the FDA rejected BioMarin’s marketing application for valrox in a surprise decision that derailed BioMarin’s hopes for a rapid rollout of the gene therapy. The company had planned to refile in the United States this month, armed with new results from a phase III trial, but was forced to postpone the filing by three months due to an FDA request for further information.

NDA Filed to Seek FDA Approval for Elacestrant in ER+/HER2- Breast Cancer

The US drug regulatory FDA received a new drug application (NDA) from Menarini Group with support from Radius. This application was filed for drug approval of elacestrant in the breast cancer patients specifically for the types – estrogen receptor-positive, HER2-negative, advanced or metastatic breast cancer treatment. The data for the application was taken from a phase 3 EMERALD trial. This trial included patients experiencing advanced or metastatic breast cancer who had ER-positive and HER2-negative diseases. In order for them to be eligible, it was required for them to have progressed or relapsed on or following 1 or 2 lines of endocrine therapy for advanced breast cancer disease, one of which was essentially needed to be given in combination with a CDK4/6 inhibitor. Another necessity was to have received at least 1 line of chemotherapy for advanced breast cancer disease, and an ECOG performance status of 0 or 1. A total number of 477 patients participated in the study, they were randomized to intake 400 mg elacestrant daily vs the investigator’s choice of anastrozole, fulvestrant, letrozole, or exemestane (SOC). 

Progression-Free Survival (PFS) was considered to be the co-primary end point of the trial in all patients and in the subgroup of patients with ESR1-mutated tumors. Whereas, key secondary endpoints included overall survival (OS) in both populations. Other secondary endpoints were PFS and OS in those without ESR1 mutations, PFS per investigator assessment, overall response rate, duration of response, and clinical benefit rate, as well as safety and tolerability. After the EMERALD study, it was found that elacestrant had a manageable safety profile which is consistent with other endocrine therapies. After the submission of the NDA, a marketing application will also be filed for elacestrant in the European Union in the second half of 2022.

AstraZeneca-Daiichi Sankyo Enhertu Breast Cancer Drug Recommended for EU Approval

AstraZeneca’s Enhertu drug has been under recommendation for approval in the European Union for patients experiencing breast cancer. The drug giant announced that Enhertu was put forward by the EU’s Committee for Medicinal Products for Human Use. It is to be used as a monotherapy for unresectable or metastatic HER2-positive breast cancer treatment in adults. It is administered specifically to patients who have received one or more prior anti-HER2-based regimens.

European Union’s decision was carried out on the fact that Enhertu displayed results showing the reduced risk of disease progression or death by 72% in comparison with the trastuzumab emtansine drug. Enhertu is developed and commercialized in collaboration with AstraZeneca and Daiichi Sankyo Co. The positive opinion was formulated on the basis of the DESTINY-Breast03 Phase III clinical trial, published in The New England Journal of Medicine.

Enhertu is a specially engineered HER2-directed antibody drug conjugate (ADC) and is being further assessed in a comprehensive clinical development program evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung, and colorectal cancers.

AbbVie Files Qulipta for Chronic Migraine Prevention

In the latest clinical development in the neurological disease segment, the AbbVie has presented a supplemental new drug application (sNDA) to the FDA. AbbVie has sought the expanded use of its newly approved CGRP receptor antagonist, Qulipta (atogepant), for the prevention of chronic migraine. AbbVie has submitted the sNDA based on the data from the pivotal phase 3 PROGRESS trial in individuals with chronic migraine. In the trial, Qulipta met its primary endpoint with a statistically significant result where it achieved a reduction of around 7 migraine days per month. With the approval of Qulipta, AbbVie is expected to extend the lead over its rivals in the Chronic Migraine segment.

Earlier, in September 2021, the FDA approved Qulipta for the preventive treatment of episodic migraine in adults. Qulipta is the first and only gepant (oral calcitonin gene-related peptide [CGRP] receptor antagonist) developed specifically for the preventive treatment of migraine. If approved for the treatment of chronic migraine, the atogepant will be the first gepant (oral calcitonin gene-related peptide [CGRP] receptor antagonist) covering a broad range of migraine indications.

Migraine is one of the most prevalent neurological diseases and a leading cause of disability, affecting nearly 39 million men, women, and children in the US and 1 billion worldwide. In the US, about 1 in 4 US households includes someone with a migraine.

FDA Approves Bristol Myers’ Breyanzi For Newly Relapsed or Refractory Large B-cell Lymphoma (LBCL) Treatment

Bristol Myers Squibb has announced that the USFDA has approved Breyanzi® (lisocabtagene maraleucel) for the treatment of adult patients with LBCL, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. Breyanzi® is a CD19-directed chimeric antigen receptor (CAR) T cell therapy. 

In the phase 3 Transform trial, Breyanzi has demonstrated clinically meaningful and statistically significant improvements in event-free survival (EFS), complete responses (CR), and progression-free survival (PFS) in patients with LBCL that is primary refractory or relapsed within 12 months after first-line therapy. Breyanzi cut the risk of event-free survival by 65.1% compared with standard chemotherapy followed by stem cell transplant. 

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) that affects B-lymphocytes. As per DelveInsight, the total incident cases of DLBCL in the 7MM were assessed to be 72,100+ in 2021, and the cases are expected to increase in the coming years. There are several treatment options for B-cell lymphoma, which include chemotherapy, radiation, and immunotherapy. With the approval of Breyanzi®, the primary refractory or relapsed LBCL treatment scenario is expected to improve immensely in the coming years. 

FDA Approves Novartis’ BRAF-positive Tumor Combination

Novartis declared that the FDA had granted accelerated approval to the pair Tafinlar and Mekinist for any advanced solid tumors with the BRAF V600E mutation. The patient must have progressed following prior therapy and have no alternative treatment options.

After melanoma, lung cancer, and thyroid cancer, Novartis’ Tafinlar-Mekinist combination can now treat any tumors regardless of their location as long as they bear a specific biomarker. The tumor-agnostic nod offers the Novartis drugs an edge over its competitor BRAF-MEK inhibitor duos, namely Pfizer’s Braftovi/Mektovi and Roche’s Zelboraf/Cotellic. The pan-tumor indication covers patients as young as 6, making it the first for a BRAF-MEK inhibitor in pediatric patients.

BRAF-MEK inhibitors are best known as the standard of care for BRAF-mutant melanoma. Over the years, the Tafinlar-Mekinist combo has added BRAF-mutant non-small cell lung cancer (NSCLC) and anaplastic thyroid cancer to its approved indications, and Pfizer’s Braftovi, used alongside Eli Lilly’s EGFR inhibitor Erbitux, expanded into BRAF-mutated colorectal cancer in 2020.

For the pan-tumor nod, Tafinlar and Mekinist showed tumor shrinkage benefits in several other cancer types in two clinical trials. Across 131 patients enrolled in the phase II ROAR study and Arm H of the NCI-MATCH trial, the Novartis combo triggered responses in biliary tract cancer, high-grade glioma, low-grade glioma, ovarian cancer, small intestine adenocarcinoma, and others.

In a small trial coded study X2101, the doublet showed an acceptable safety profile and some tumor shrinkage ability in pediatric patients, mainly those with pretreated glioma. BRAF V600E is the most common BRAF mutation, making up about 90% of all BRAF-mutant cancers. BRAF mutations have been identified in more than 20 tumor types.

Last year, Tafinlar and Mekinist reeled in $1.69 billion in sales, suitable for 8% growth at constant currencies. Approvals mainly drove the increase in the post-surgery adjuvant treatment of melanoma and metastatic NSCLC. The rival BRAF-MEK drugs are much smaller assets on the sales metric.

FDA accelerated approval means Novartis will need to offer verification of the combo’s benefit in a confirmatory trial. As Novartis noted, given the rarity of the mutation, it may be challenging to run phase III trials in some BRAF-driven tumor subtypes.

Novartis may already have confirmatory evidence for pediatric glioma patients, potentially allowing it to reach an even younger population. In children as young as 1, Tafinlar and Mekinist cut the risk of progression or death by 69% over chemotherapy when given as the first systemic treatment for BRAF V600 pediatric low-grade glioma. Earlier this month, Novartis presented the phase II/III TADPOLE trial data at the 2022 American Society of Clinical Oncology annual meeting. In a single-arm cohort of children with relapsed/refractory BRAF V600 high-grade gliomas, the Novartis combo showed a response rate of 56.1%.

GSK’s Hepatitis B Hope Bepirovirsen Heads for Phase 3 Test

GSK has taken a step toward its goal of providing a functional cure to hepatitis B patients. After 24 weeks of treatment, almost 30% of participants in phase 2b clinical trial had undetectable virus levels, ramping up expectations ahead of the delivery of data on durability and starting a pivotal study.

The hepatitis B treatment toolkit currently centers on interferon-type molecules and nu­cle­o­side analogs such as entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide. Interferon molecules boost the immune system, and nu­cle­o­side analogs stop or slow virus replication. Yet, even when used in combination, only a tiny percentage of patients have undetectable hepatitis B surface antigen levels.

GSK, having paid Ionis Pharmaceuticals $25 million upfront in 2019, is one of a set of companies trying to ramp up the percentage of patients with undetectable levels of the antigen. Big Pharma used the European Association for the Study of the Liver’s International Liver Congress 2022 to showcase its work on the antisense therapy bepirovirsen.

In an interim analysis of the phase 2b B-Clear clinical trial, GSK found undetectable levels of hepatitis B surface antigen and DNA in almost 30% of participants who received 300 mg bepirovirsen for 24 weeks, regardless of whether they were also taking nu­cle­o­side analogs. The figures were 28% in the nu­cle­o­side analog combination arm and 29% in the bepirovirsen single-agent cohorts. 

The figures suggest the bepirovirsen may improve the standard of care while leaving room to improve and unanswered questions. The critical question that GSK is still assessing is whether the responses are durable. Suppose responders can come off bepirovirsen and keep the virus in check. In that case, GSK may be on course to deliver a functional cure, at least for the minority of patients who respond to single-agent therapy.

Another critical question is how to help more than 70% of patients with detectable levels of hepatitis B. GSK is looking to combinations to boost the response rate, with midphase trials of bepirovirsen alongside pegylated interferon and targeted immunotherapy on its roster of hepatitis B studies. 

The combination work will advance parallel to a push to validate the effect of bepirovirsen as a single agent. A phase III monotherapy study will start in the first half of next year, positioning GSK to show whether it can replicate the phase 2b response rate in a larger trial. GSK sees a 2 billion pound sterling ($2.5 billion)-plus the global opportunity for the drug but faces competition from rivals, including Johnson & Johnson.