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Patrick Lavery

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The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has given a positive opinion to Roche extending its marketing authorization for Vabysmo (faricimab) to include treatment of visual impairment due to macular edema, secondary to retinal vein occlusion (RVO) (1). A press release from Roche on June 28, 2024 said the European Commission (EC) would be making a final decision on approval “in the near future,” though did not specify a date.

Vabysmo was earlier approved for RVO by FDA in October 2023 and the Japan Ministry of Health, Labour and Welfare in March 2024. It is also approved in nearly 100 countries around the world for those living with neovascular, or “wet,” age-related macular degeneration or diabetic macular edema (1).

Roche said RVO is the second-most common cause of vision loss when it comes to retinal vascular diseases, often sudden and severe, and affecting approximately 28 million adults worldwide, most age 60 and above (1). RVO itself is painless to the affected eye, as vein blockage restricts normal blood flow to the retina—resulting in macular edema, ischemia, bleeding, and fluid leakage—but is traditionally treated with a series of intravitreal injections of anti-vascular endothelial growth factor therapies. Vabysmo, if approved in Europe, would be the first bispecific antibody treatment for nearly 1 million people with RVO across the European Union, according to Roche.

“This CHMP recommendation represents an important step towards bringing Vabysmo to even more patients living with vision loss in Europe,” Levi Garraway, MD, PhD, Roche chief medical officer and head of global product development, said in the press release. “Recognizing the disruptive impact retinal vein occlusion can have on the everyday lives and independence of these patients, we hope that Vabysmo will offer a new treatment option that can effectively help preserve and improve their vision.”

CHMP’s decision followed the release of 72-week data from two Phase III students (BALATON, COMINO) that evaluated the performance of Vabysmo in more than 1200 patients with macular edema attributable to one of the two main types of RVO: branch RVO, when one of four smaller “branches” of the main central retinal vein is blocked, and the less common central RVO, when the central retinal vein itself becomes blocked (1,2,3). Both studies showed early, sustained vision improvements along with “robust” retinal drying, Roche said.

Current treatments for RVO are given every one to two months; the Vabysmo studies administered six monthly treatments over the first 20 weeks, then up to every four months from weeks 24 to 72 (1).

1. F. Hoffman-La Roche. Roche’s Vabysmo Gets CHMP Recommendation for Third Indication Retinal Vein Occlusion (RVO). Press Release. June 28, 2024.
2. ClinicalTrials.gov. Study Details | A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Macular Edema Secondary to Branch Retinal Vein Occlusion (BALATON). 

, Jan. 18, 2024 (accessed June 28, 2024). 


3. ClinicalTrials.gov. Study Details | A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Macular Edema Secondary to Central Retinal or Hemiretinal Vein Occlusion (COMINO). 

Articles

Vabysmo, already approved for patients with RVO in the US and Japan, would be the first bispecific antibody treatment for the condition in Europe.

Roche Attains European Recommendation for Retinal Vein Occlusion Treatment

Data from a Pan-European Real Life (PEARL) Phase IV study of fremanezumab, which is marketed by Teva Pharmaceutical Industries as Ajovy, may challenge prevalent opinions on treatment pauses in adult patients with episodic or chronic migraines, according to a press release from Teva on June 28, 2024 (1).

Such pauses, Teva said, are recommended or even mandated for calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs; fremanezumab is a CGRP-pathway mAb) by some reimbursement authorities after one year of continuous use (1). However, the data showed that pausing treatment with fremanezumab may result in increased monthly migraine days (MMDs), when treatment is typically ceased and reinitiated, and decreased effectiveness when the treatment is resumed.

More specifically, the study found that more than 40% of patients reported a rapid worsening of their migraines, or greater than or equal to a 50% increase in MMD, at months 1 and 2 post-cessation, while the proportion of patients who had greater than or equal to a 50% reduction in MMD in months 1 and 3, respectively, was 49.0% and 58.9% in the first treatment period before cessation, versus 35.7% and 45.5% in the second period after reinitiation (1).

“The PEARL Study analysis is significant for clinicians treating people with episodic and chronic migraine as it shows that treatment cessation and reinitiation can disrupt the progress made in managing the condition in some of them,” said Dimos Mitsikostas, professor of neurology, Aeginition Hospital, Medical School of the National & Kapodistrian University of Athens, in the press release. Mitsikostas is presenting the study data at the European Academy of Neurology in Helsinki, Finland, beginning June 29, 2024 (2). “It is important that we are guided by the evidence and adopt a more personalized treatment approach and not a ‘one-size-fits-all’ strategy in helping people with migraine long-term.”

“This new sub-analysis may challenge the rationale for mandatory treatment pauses and highlights the potential for these breaks to diminish the benefits achieved in reducing migraine for some patients," said Pinar Kokturk, MD, vice president and head of medical affairs for Teva in Europe. “The PEARL study demonstrates the long-term effectiveness and safety of fremanezumab in preventing both episodic and chronic migraine in a real-world setting and underscores the benefit of treatment continuity and individualized, uninterrupted patient management strategies.”

A consensus on halting migraine therapy has been difficult to ascertain. The European Headache Federation suggests a pause after 12 to 18 months of treatment—but recommends continuing indefinitely, if necessary. Some countries, across Europe and elsewhere, mandate one-year treatment pauses, primarily because of differing reimbursement conditions (1). Still elsewhere, one literature review suggests stopping the use of CGRP-pathway mAbs as soon as a lack of remaining need for prevention is necessary, meaning fewer than four MMDs.

Ajovy is indicated for prophylaxis of migraines in adults who have four MMDs per month or greater. It is a subcutaneous injection that can be administered either by a healthcare professional, or at home by a patient or caregiver.

1. Teva Pharmaceutical Industries. New AJOVY (fremanezumab) Migraine Prevention Data Challenges Treatment Pauses. Press Release. June 28, 2024.
2. Mitsikostas, D.; et al. Impact of Fremanezumab Cessation and Reinitiation in Migraine Management: PEARL Study 4th Interim Analysis. Presentation at European Academy of Neurology, Helsinki, Finland, June 29–July 2, 2024.

The typical cycle of ceasing and then reinitiating fremanezumab treatments may actually result in increased monthly migraine days, the study said.

Data from Study of Teva’s Ajovy Suggests Change to Migraine Treatment Pause Protocols

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Lantheus Holdings announced on June 27, 2024 that it had acquired global rights to an RM2 licensed to Life Molecular Imaging, originally developed by Bayer, that targets the gastrin-releasing peptide receptor (GRPR) (1). The acquisition includes the novel, clinical-stage radiotherapeutic and radiodiagnostic pair 

Life Molecular defines an RM2 as a small peptide that binds with high affinity to the GRPR (2). It is highly expressed in early and recurrent prostate and other cancers, and in the press release announcing the acquisition, Lantheus mentioned prostate and breast cancers as two types that the radiotheranostic pair would be used to target (1).

Further expanding upon that, Lantheus said 

Ga-DOTA-RM2 also targets lung, pancreatic, colorectal, gastric, and ovarian cancers, all of which along with prostate and breast cancer overexpress GRPR (1,3). The first dosimetry in humans, according to Lantheus, yielded favorable dosimetry and safety profiles, also confirming preclinical data that showed the dose-dependent efficacy of 

GRPR is known to help regulate gastrointestinal movement, gastric emptying, smooth muscle contraction, and trypsin release and is involved in not only immune functions but also those of the brain, including memory, circadian rhythm, and the modulation of stress, fear, and anxiety (3).

The companies on both sides of the announcement applauded the acquisition, which was made for an upfront price of $35 million, plus potential regulatory milestone payments, with royalties.

“While new PSMA [prostate-specific membrane antigen]-targeted diagnostics and therapeutics are transforming prostate cancer care, there are many patients for whom PSMA-targeted therapy may not be appropriate,” Brian Markison, Lantheus CEO, said in the press release. “Targeting GRPR with 

Ga-DOTA-RM2 creates a potential new option to expand access to radiotheranostics for more prostate cancer patients. This expands our therapeutic offerings and opens avenues for commercial synergies.”

“With Lantheus’ experience developing and providing access to radiotheranostics in cancer, we are confident in our decision to hand them the reins for this promising theranostic pair and are honored to work with them toward improving the future for people with prostate and breast cancer,” Ludger Dinkelborg, CEO of Life Molecular, said.

Lantheus said it will begin a Phase I/IIa study with 

Lu-DOTA-RM2 in prostate cancer patients in 2025, with 

Ga-DOTA-RM2 used as a companion diagnostic (1). Life Molecular will continue to collaborate with Lantheus, according to the release, to complete the Phase I/IIa dose escalation study.

1. Lantheus Holdings. Lantheus Acquires Global Rights to Life Molecular Imaging’s Novel Therapeutic and Diagnostic Pair Targeting GRPR for Prostate and Breast Cancers. Press Release. June 27, 2024.
2. Life Molecular Imaging. Life Molecular Imaging Announces Presentation of New Scientific Data at the European Association of Nuclear Medicine Annual Meeting 2022. Press Release. Oct. 14, 2022.
3. Ma, Y. and Gao, F. Advances of Radiolabeled GRPR Ligands for PET/CT Imaging of Cancers. 

GRPR, or gastrin-releasing peptide receptor, is part of the bombesin G protein-coupled receptor family and has been found to be overexpressed in multiple cancers.

Lantheus Acquires Rights to Life Molecular’s RM2 Targeting GRPR for Prostate and Breast Cancers

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Cellares announced on June 27, 2024 that it has entered into an agreement with Kite, a Gilead Company, to evaluate the Cell Shuttle, Cellares’ automated manufacturing platform. A press release from Cellares said that the proof-of-concept evaluation, and the data generated from it, would be used to assess how viable the Cell Shuttle would be for Kite to employ as a manufacturing option (1).

According to Cellares, the Cell Shuttle integrates technologies required for drug manufacturing “in a flexible and high-throughput platform” that is automated end-to-end, or “walk-away” (1). The company has what it calls “Smart Factories,” at its South San Francisco, Calif. headquarters and a commercial-scale facility in Bridgewater, NJ, and plans to use Cell Shuttles at other Smart Factories around the world to help meet patient demand for cell therapies.

“This agreement with Kite allows the unique capabilities of our Cell Shuttle platform to be potentially utilized by Kite in the future and reinforces Cellares’ position as a cell therapy manufacturer with advanced automated technology,” said Fabian Gerlinghaus, Cellares co-founder and CEO, in the press release. “We aim to fully automate all cell therapy manufacturing processes, moving us closer to delivering CAR [chimeric antigen receptor] T-cell therapies for a wide range of autoimmune diseases and cancers. We are honored to work with an industry leader such as Kite, that already is serving patients worldwide with two commercially approved cell therapies.”

“Given that manufacturing is central to how we deliver CAR T-cell therapies to physicians and patients, we are always assessing what technologies could further enhance our best-in-class manufacturing capabilities,” Kite senior vice president and global head of technical operations Chris McDonald said, also in the press release. “We welcome this opportunity to evaluate Cellares’ automation production platform for how it potentially could help us reach even more patients with our next-generation therapies.”

Kite, a subsidiary of Gilead, has headquarters in Santa Monica, Calif., and the focus of its business is cell therapy to treat and cure cancer, specifically using a patient’s own white blood cells to target and attack their cancer cells (2). Cellares describes itself as the first integrated development and manufacturing organization devoted to cell therapy manufacturing both at the clinical level and on an industrial scale, adding that its partners in research, industry, and academia benefit from accelerated development, and lower failure rates and manufacturing costs (1).

No specific timeframe was given for the expected length of Kite’s evaluation or when data from it might be known. Cellares said the pact with Kite follows a $380 million supply agreement reached with Bristol Myers Squibb in May 2024, and other recently announced partnerships with Cabalette Bio and Lyell Immunopharma (3).

1. Cellares. Cellares Announces Agreement with Kite to Evaluate Its Cell Shuttle Automated Manufacturing Platform. Press Release. June 27, 2024.
2. Gilead Sciences. Transformational Cancer Treatment | Kite Pharma. 

 (accessed June 27, 2024).
3. Comment received via email correspondence on June 27, 2024.

No timetable was given for the length of the planned evaluation or when data would be available, but Kite intends to use the information to expand its manufacturing options.

Kite to Evaluate Cellares’ Manufacturing Platform for Wider Use

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The National Medical Products Administration (NMPA) in China has approved Tagrisso (osimertinib), a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) developed by AstraZeneca, in combination with pemetrexed and platinum-based chemotherapy, for first-line treatment of adult patients with locally advanced, or metastatic, EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) with tumors with exon 19 deletions or exon 21 (L858R) mutations (1). AstraZeneca announced the approval in a press release on June 26, 2024.

While Tagrisso is approved as monotherapy in more than 100 countries including China, the United States, Japan, and across the European Union, according to AstraZeneca, its use as specifically stated in the new decision from the NMPA—that is, in conjunction with chemotherapy for first-line treatment of patients with EGFRm NSCLC—is less widely approved, although the US is also one of those such countries (1).

The approval in China comes after results of a Phase III trial (FLAURA2) were published in 

 in addition to results from an exploratory subgroup of Chinese patients, which were presented at the European Society for Medical Oncology Asia Congress 2023 (1,2).

“The approval of osimertinib with the addition of chemotherapy in China is critical for the treatment of the largest population of patients with EGFR-mutated lung cancer worldwide,” said Ying Cheng, MD, director of Jilin Lung Cancer Diagnosis and Treatment Centre, and principal investigator in the Phase III trial in China, in the AstraZeneca press release. “These patients will now have a choice of two highly effective osimertinib-based options for first-line treatment, allowing physicians to tailor their approach to their patients. This is especially important for those with a poorer prognosis, such as cancer that has spread to the brain or those who have L858R mutations.”

Also commenting on the latest approval was Dave Fredrickson, executive vice-president of AstraZeneca’s oncology business unit, who stated in the press release: “Tagrisso with the addition of chemotherapy in FLAURA2 has not only shown unprecedented progression-free survival in the overall trial population, but also among Chinese patients, reducing the risk of disease progression by nearly half.”

“This approval reinforces Tagrisso as a backbone therapy in EGFR-mutated lung cancer and acknowledges its important role, as monotherapy or with chemotherapy, in addressing the high prevalence of this disease in Asian countries and China, specifically,” Fredrickson added.

More than 1 million people in China are diagnosed with lung cancer annually, according to AstraZeneca, accounting for more than one-third of lung cancer patients worldwide (1). Of those with NSCLC, which is the disease’s most common form, about 40% of Chinese patients have tumors with an EGFR mutation—and the majority are diagnosed with advanced disease.

However, Fredrickson pointed out in the release, in the China cohort of the Phase III trial, Tagrisso in combination with chemotherapy reduced the risk of disease progression or death by 44% compared to Tagrisso monotherapy, and extended the median progression-free survival from 22.3 to 27.4 months (1).

1. AstraZeneca. Tagrisso with the Addition of Chemotherapy Approved in China as 1st-Line Treatment for Patients with EGFR-Mutated Advanced Lung Cancer. Press Release. June 26, 2024.
2. Planchard, D.; Jänne, P.A.; Cheng, Y.; et al. Osimertinib With or Without Chemotherapy in EGFR-Mutated Advanced NSCLC. 

Results of a Phase III trial showed that Tagrisso with the addition of chemotherapy reduced the risk of disease progression or death associated with EGFR-mutated non-small cell lung cancer by 44%.

AstraZeneca Lung Cancer Treatment Approved in China

The European Commission (EC) has approved Fruzaqla (fruquintinib) as a monotherapy for adult patients diagnosed with metastatic colorectal cancer (CRC) previously treated with other available, standard therapies (1).

China-based drug discovery company Hutchmed announced on June 21, 2024 that its partner Takeda, which has the exclusive license to develop, manufacture, and bring fruquintinib to market outside of mainland China, Hong Kong, and Macau, had received EC approval, which followed approval in the United States in November 2023 (2).

In a press release, Hutchmed said Fruzaqla, which is also the drug’s brand name in the US, is the European Union’s first novel targeted therapy for metastatic CRC, regardless of biomarker status, in more than a decade (1).

Standard therapies identified by Hutchmed as those with which CRC patients may have been treated prior to receiving Fruzaqla include fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapies, anti-vascular endothelial growth factor (anti-VEGF) agents, and anti-epidermal growth factor receptor agents. The patients typically have progressed on, or are intolerant to, treatment with either trifluridine-tipiracil or regorafenib, Hutchmed said (1).

Fruquintinib is a selective oral inhibitor of all three VEGF receptors (VEGFR-1, -2, and -3) and, as such, is key to inhibiting tumor angiogenesis, according to the press release.

Weiguo Su, PhD, Hutchmed chief executive officer and chief scientific officer, said that expanding this therapeutic option’s reach was a “significant milestone,” as metastatic CRC is an area of largely unmet need with few effective treatments available.

“This novel oncology medicine is currently improving the treatment outlook in the US and China, and we look forward to seeing its impact for patients across Europe,” Su said in the press release.

Takeda global oncology business unit president Teresa Bitetti agreed, stating in the press release, “Patients in Europe with metastatic colorectal cancer have long needed additional treatment options, and we are grateful to be able to meet that need thanks to our partnership with Hutchmed.”

CRC begins in either the colon or rectum and is the third-most prevalent cancer worldwide, and the second-most common in Europe as of 2022, according to the World Health Organization and the International Agency for Research on Cancer (1). The EC approval came after a positive opinion from the Committee for Medicinal Products for Human Use in April 2024, which in turn was based on results from a Phase III multiregional (US, Europe, Japan, and Australia) clinical trial (FRESCO-2) (3).

Experts in the oncology field in Europe are hopeful this approval will make an immediate impact. “There is a clear need in Europe for patients and their clinicians to be able to access a new treatment option for previously treated metastatic colorectal cancer, and we are excited that this important step has been taken so that we can begin prescribing this new and differentiated medicine,” Josep Tabernero, MD, PhD, director of Vall d’Hebron Institute of Oncology, said in the Hutchmed press release.

Hutchmed. HUTCHMED Announces European Commission Approval for FRUZAQLA (fruquintinib) Received by Takeda. Press Release. June 21, 2024.

Hutchmed. HUTCHMED Announces that Takeda Receives U.S. FDA Approval of FRUZAQLA (fruquintinib) for Previously Treated Metastatic Colorectal Cancer. Press Release. Nov. 8, 2023.

Dasari, A.; Lonardi, S.; Garcia-Carbonero, R.; et al. Fruquintinib Versus Placebo in Patients with Refractory Metastatic Colorectal Cancer (FRESCO-2): An International, Multicentre, Randomised, Double-Blind, Phase 3 Study. 

Fruzaqla was previously approved for use in patients with metastatic colorectal cancer in the US in November 2023.