Merck & Pfizer’s BAVENCIO® ▼ (avelumab) now recommended as an option as a maintenance therapy for eligible patients with locally advanced or metastatic urothelial carcinoma following NICE appeal

Merck & Pfizer’s BAVENCIO^® ▼ (avelumab) now recommended as an option as a maintenance therapy for eligible patients with locally advanced or metastatic urothelial carcinoma following NICE appeal

Today Merck and Pfizer announce that, following a successful appeal of the prior Final Appraisal Document (FAD), the National Institute for Health and Care Excellence (NICE) has overturned its decision and now recommends the immunotherapy BAVENCIO^® (avelumab) as a maintenance treatment option in eligible adult patients with locally advanced or metastatic urothelial carcinoma (UC),ⁱ also known as bladder cancer.^[iii]

The decision is welcomed as avelumab is the first and only monotherapy for the first-line maintenance treatment of adult patients with locally advanced or metastatic UC who are progression-free following platinum-based chemotherapy^[iv] and now offers a further treatment option for these patients.¹ The NICE recommendation enables eligible patients in England, Wales and Northern Ireland to access this treatment via routine NHS funding. Interim funding via the Cancer Drugs Fund will enable reimbursement of avelumab until NICE final guidance is published and funded after a 30-day mandatory period.

Lydia Makaroff of Fight Bladder Cancer, explains: "We are delighted with this decision. Until now, there was no maintenance treatment available on the NHS in England, Wales and Northern Ireland for advanced bladder cancer after chemotherapy. This positive decision may have the potential to give hundreds of people with terminal bladder cancer more good quality time with their loved ones."

Bladder cancer is the 11^th most common cancer in the UK and the 10^th most common cause of cancer death.^[v] UC, which accounts for 90% of bladder cancer cases,^[vi] has poor survival outcomes.^[vii] The one-year survival rate for bladder cancer is the lowest for those patients diagnosed with advanced bladder cancer (stage 4), with only 36% of patients at stage 4 surviving for at least one year.^vii

Dr Simon Crabb, Associate Professor in Medical Oncology, Cancer Sciences, University of Southampton Faculty of Medicine, states: “This is the only first-line maintenance monotherapy for advanced urothelial carcinoma following platinum-based chemotherapy and is a significant step forward in treating these patients with high unmet needs. NICE’s decision will provide healthcare professionals with an additional treatment option to help sustain and extend the benefits of platinum-based chemotherapy, potentially increasing overall survival and – importantly – without negatively affecting the patients’ quality of life.”

Bladder cancer has high recurrence rates (up to 74.3%),^[viii] with most patients ultimately experiencing disease progression within nine months of initiation of first-line chemotherapy treatment.^[ix],[x]^,[xi] The Phase III JAVELIN Bladder 100 study demonstrated that if patients, whose cancer does not progress after initial platinum-based chemotherapy, are given avelumab as maintenance treatment, together with best supportive care (BSC), it takes longer for their cancer to get worse, and they live longer than if they have BSC alone.^[xii],[xiii]

 

“We are very pleased that NICE’s revised decision to recommend avelumab as a maintenance treatment option for advanced bladder cancer means that eligible patients now have access to this much-needed treatment.” said Dr Stuart Hill, Medical Director, Merck UK & Ireland. “The Merck-Pfizer Alliance is particularly grateful for the support of both the patient and clinical communities who came together during the process to highlight the need for physicians to be able to initiate patients on this innovative treatment approach.”

 

Results from the Phase III JAVELIN Bladder 100 study, that were submitted to NICE (interim data from a cut-off date of 21 October 2019), demonstrated a statistically significant 7.1-month improvement in median overall survival (OS) for the whole trial population with avelumab plus BSC compared with BSC alone (21.4 months (95% Confidence Interval (CI): 18.9 to 26.1) vs. 14.3 months (95% CI: 12.9 to 17.9)). The median duration of trial treatment was 24.9 weeks (range, 2.0 to 159.9) in the avelumab group and 13.1 weeks (range, 0.1 to 155.6) in the control group.¹³ This statistically significant improvement in median OS represents a 31% reduction in the risk of death in favour of avelumab + BSC compared with BSC alone (Hazard Ratio (HR): 0.69; 95% CI: 0.56 to 0.86; 2-sided p-value=0.001).^iv,xiii Long-term follow-up data presented at the 2022 ASCO Genitourinary Cancers Symposium showed that median OS in the overall population was 23.8 months (95% CI: 19.9 to 28.8) in the avelumab + BSC arm vs 15.0 months (95% CI: 13.5 to 18.2) in the BSC alone arm (HR: 0.76 [0.631-0.915]; 2-sided p-value=0.0036), from a data cut-off date of 4 June 2021. The median duration of avelumab treatment was 25.3 weeks (range 2.0-216.0).^[xiv]

JAVELIN Bladder 100 study and the longer term follow up data found evidence to support both avelumab efficacy and safety and demonstrated an improvement in the median overall survival for eligible patients with locally advanced or metastatic bladder cancer in maintenance avelumab plus BSC compared to BSC alone.^xiii,[xv] The most common adverse events (AEs) of any grade and from any cause, that occurred in ≥10% patients in the avelumab group, include fatigue (n=61 [17.7%]) and pruritis (n=59 [17.2%]).^xiii 101 (29.4%) avelumab-treated patients had an adverse event that was categorised as being immune-related.¹³ The most frequent category of immune-related adverse events was thyroid disorders (n=42 [12.2%]).^xiii High dose glucocorticoids were administered after an immune-related adverse event in 31 patients (9.0%) who received avelumab.¹³ Long-term follow-up data identified no new safety signals or concerns.^xiv 

Dr Olivia Ashman, Oncology Medical Director, Pfizer UK explains: “We’re delighted to now have both the NICE and SMC recommendations for avelumab as a first-line maintenance therapy in advanced bladder cancer, enabling all eligible patients in the UK to have routine access to this innovative treatment on the NHS.  We’re committed to advancing science as well as ensuring access to the resulting treatments to improve the outlook for people living with cancer.”

 

Further information on BAVENCIO^® (avelumab) can be found in the SmPC: https://www.medicines.org.uk/emc/product/8453/smpc#gref.

 

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events.  Reporting forms and information can be found at mhra.gov.uk/yellowcard. Adverse events should also be reported to Merck Serono Limited on 0208 818 7373 (email: medinfo.uk@merckgroup.com).

 

About JAVELIN Bladder 100 Study

JAVELIN Bladder 100 (NCT02603432) is a Phase III, multicentre, multinational, randomised, open-label, parallel-arm study investigating first-line maintenance treatment with avelumab plus best supportive care (BSC) versus BSC alone in patients with locally advanced or metastatic UC. A total of 700 patients whose disease had not progressed after platinum-based induction chemotherapy as per RECIST v1.1 were randomly assigned to receive either avelumab plus BSC or BSC alone. The primary endpoint was OS in the two primary populations of all patients and patients with PD-L1+ tumours.^xiii

 

The most common adverse events reported in the study were fatigue, pruritis, urinary tract infection, diarrhoea, arthralgia, asthenia, constipation, back pain, nausea, pyrexia, decreased appetite, cough, vomiting, hypothyroidism, rash, anaemia, haematuria and infusion-related reaction.¹³ Long-term follow-up data identified no new safety signals or concerns.^xiv

 

About BAVENCIO^® (avelumab)

Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.^{[xvi],[xvii],[xviii]} In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialise avelumab. 

 

BAVENCIO^® (avelumab) Approved Indications in UK

In the UK, avelumab is already recommend for use in patients with merkel cell carcinoma (MCC)^[xix] and advanced renal cell carcinoma (aRCC).^[xx] It was also approved for use in patients with Urothelial Carcinoma (UC) in Scotland in August 2021.ⁱⁱ

 

BAVENCIO^® (avelumab) Safety Profile

Avelumab is subject to additional monitoring.^xv The special warnings and precautions for use for avelumab monotherapy include infusion-related reactions, as well as immune-related adverse reactions (IRAEs). IRAEs include pneumonitis and hepatitis (including fatal cases), colitis, pancreatitis (including fatal cases), myocarditis (including fatal cases), endocrinopathies, nephritis and renal dysfunction, and other IRAEs.^xv

 

The summary of products characteristics (SmPC) list of the most common adverse reactions with avelumab monotherapy in patients with solid tumours includes fatigue, nausea, diarrhoea, decreased appetite, constipation, infusion-related reactions, weight decrease, vomiting, anaemia, cough, dyspnoea, abdominal pain, back pain, arthralgia, pyrexia, and peripheral oedema.^15xv

 

About PD-L1

PD-L1 is a protein expressed on the surface of cells, which binds to PD-1 receptors on T cells of the immune system to stop them from attacking them.^xvi,[xxi] Some tumour cells also have PD-L1 proteins on their surface^xxi (‘PD-L1 positive’ status),^xvi preventing the immune T cells from recognising and attacking them.^xxi Avelumab is an antibody which binds to PD-L1 on tumour cells and blocks it from binding to the PD-1 receptors on T cells,^xviii allowing the immune system T cells to recognise and kill the cancer cells.^xviii,xxi

 

About the Merck-Pfizer Alliance

The global strategic alliance between Merck and Pfizer enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of avelumab, an anti-PD-L1 antibody initially discovered and developed by Merck. The immuno-oncology alliance will jointly develop and commercialise avelumab. The alliance is focused on developing high-priority international clinical programmes to investigate avelumab as a monotherapy, as well as in combination regimens, and is striving to find new ways to treat cancer.

 

About Merck

Merck, a leading science and technology company, operates across healthcare, life science and electronics. Around 58,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From advancing gene editing technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2021, Merck generated sales of € 19.7 billion in 66 countries.

 

Scientific exploration and responsible entrepreneurship have been key to Merck’s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD Electronics.

 

Pfizer: Breakthroughs that change patients’ lives

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. In the UK, Pfizer has its business headquarters in Surrey and is a major supplier of medicines to the NHS. To learn more about our commitments, please visit us at www.pfizer.co.uk or follow us on Twitter (@Pfizer_UK), Facebook (@PfizerUK) and Instagram (@pfizeruk).

 

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[iii] Cancer Research UK. Types. Available at: https://www.cancerresearchuk.org/about-cancer/bladder-cancer/types-stages-grades/types [Accessed April 2022]

[iv] NICE. Technology appraisal. Avelumab for maintenance treatment of locally advanced or metastatic urothelial cancer after platinum-based chemotherapy [ID3735]. Available at: https://www.nice.org.uk/guidance/gid-ta10624/documents/committee-papers. [Accessed April 2022]

[v] Cancer Research UK. Bladder cancer statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer#heading-Zero. [Accessed April 2022]

[vi] Chalasani V, et al. Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer. Can Urol Assoc J. 2009; 8; 193–8.

[vii] Cancer Research UK. Bladder Cancer Survival Statistics - adults diagnosed 2013-2017, followed up to 2018. Bladder cancer survival by stage at diagnosis. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer/survival#heading-Three. [Accessed April 2022]

[viii] Chamie K, et al. Recurrence of high-risk bladder cancer: A population-based analysis. Cancer. 2013 ;119(17) :3219–27. doi: 10.1002/cncr.28147.

[ix] Dogliotti L, et al. Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol. 2007;52:134–41.

[x] Von der Maase H, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 2005;23:4602–8.

[xi] Von der Maase H, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Onc 2000;18:3068–77.

[xii] NICE. Final Appraisal Document. Avelumab for maintenance treatment of locally advanced or metastatic urothelial cancer after platinum-based chemotherapy. Available at: https://www.nice.org.uk/guidance/gid-ta10624/documents/final-appraisal-determination-document. [Accessed April 2022]

[xiii] Powles T, et. Al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-30. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18. PMID: 32945632.

[xiv] Powles T, et al. Avelumab first-line maintenance for advanced urothelial carcinoma: long-term follow-up results from the JAVELIN Bladder 100 trial. Abstract no. 487. Presented at the 2022 ASCO Genitourinary Cancers Symposium. February 17-19, 2022; San Francisco, CA; Hybrid.

[xv] BAVENCIO^® (avelumab) UK SmPC Electronic Medicines Compendium. (EMC). Bavencio 20 mg/mL concentrate for solution for infusion. Available at: https://www.medicines.org.uk/emc/product/8453/smpc. [Accessed April 2022]

[xvi] Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control. 2014;21(3):231–7.

[xvii] Dahan R, Sega E, Engelhardt J, et al. FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell. 2015;28(3):285–95.

[xviii] Boyerinas B, Jochems C, Fantini M, et al. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res. 2015;3(10):1148–57.

[xix] NICE. Avelumab for untreated metastatic Merkel cell carcinoma. Final appraisal document. Available at: https://www.nice.org.uk/guidance/ta691/documents/final-appraisal-determination-document [Accessed April 2022]

[xx] NICE. Avelumab with axitinib for untreated advanced renal cell carcinoma. Final appraisal document. Available at: https://www.nice.org.uk/guidance/ta645/documents/final-appraisal-determination-document [Accessed April 2022]

[xxi] National Cancer Institute. Definition of PD-L1 - NCI Dictionary of Cancer Terms. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/pd-l1 [Accessed April 2022]