Bristol Myers Squibb 2021: In the big leagues now

Five years after bottoming out, Bristol Myers Squibb has moved to the first division of pharma companies with three of the world’s top eight drugs in its portfolio.

By Joshua Slatko • [email protected]

 

 

Bristol Myers Squibb

430 E. 29th Street, 14th Floor

New York, NY 10016

Telephone: 212-546-4000

Website: bms.com

 

OUTCOMES CREATIVITY INDEX SCORE: 6

Manny Awards — 2

Cannes Lions — N/A

Clio Health — N/A

Creative Floor Awards — 4 

MM+M Awards — N/A

One Show — N/A

 

Financial Performance

(All figures are in millions of dollars, except EPS.)

2020  

Revenue $42,518  

Net income $(8,995)  

Diluted EPS $(3.99)  

R&D expense $11,143  

1H 2021  

Revenue $22,776  

Net income $3,090  

Diluted EPS $1.36 

R&D expense $5,496  

Best-Selling Products

(All sales are in millions of dollars.)

2020  

Revlimid $12,106  

Eliquis $9,168  

Opdivo $6,992  

Orencia $3,157  

Pomalyst/Imnovid $3,070  

Sprycel $2,140  

Yervoy $1,682  

Abraxane $1,247  

1H 2021  

Revlimid $6,146 

Eliquis $5,678  

Opdivo $3,630  

Pomalyst/Imnovid $1,627  

Orencia $1,572  

Sprycel $1,011  

Yervoy $966 

Abraxane $610  

 

Pharma companies often say that they’ve been transformed in one manner or another, but few of them ever mean it quite as much as the Bristol Myers Squibb of 2020 did. In the first full year after completion of the Celgene acquisition, the company now has in its portfolio the third (Revlimid), fourth (Eliquis), and eighth (Opdivo) best-selling prescription products in the world, not to mention a pile of new approvals coming out of the pipeline and an Opdivo development program that continues to chug along, with four more FDA approvals coming during 2021. All in all, not bad from a company whose leading product just five years ago was the $2 billion, going-off-patent Abilify. 

“The first year of our new company was truly a remarkable time in BMS history,” said CEO Giovanni Caforio, M.D. in the company’s annual report. “We created a leading biopharma company, a diversified company with leading medicines across oncology, hematology, immunology, and cardiovascular. One with a broad and deep pipeline, and the financial flexibility to continue to invest in innovation. And one where the best people in the industry are committed to our mission to discover, develop, and deliver innovative medicines to patients who need them.”

In its first full year post-Celgene acquisition, BMS’ top-line revenue was $42.52 billion, 62.6 percent better than the previous year. The company took a net loss of $9 billion for 2020, with earnings per share of negative $3.99. This was impacted, of course, by one-time charges related to the Celgene and MyoKardia (November 2020) transactions of more than $20 billion; company leaders estimated an increase in EPS of $1.75 after adjusting for these items. In the first half of 2021 BMS generated top-line revenue of $22.78 billion, with net income of $3.09 billion and EPS of $1.36, after having taken a net loss of $846 million in the first half of 2020. BMS executives are projecting that full-year EPS for 2021 will fall in the $2.77-$2.97 range. 

Partnerships & Acquisitions

In February, BMS and The Rockefeller University announced a definitive agreement under which Bristol Myers Squibb was granted a global exclusive license to develop, manufacture, and commercialize Rockefeller’s novel monoclonal antibody (“mAb”) duo treatment that neutralizes the SARS-CoV-2 virus for therapy or prevention of COVID-19. Phase I clinical trials to assess dosing for IV and subcutaneous formulations, and to assess safety for the mAb duo, were initiated by Rockefeller in mid-January. Planning is underway with the goal of moving rapidly to a registrational program following readout of the Phase I study taking place at Rockefeller University Hospital. Included in the terms of the agreement, Rockefeller is entitled to receive royalty payments on future sales. Should the clinical development be successful, Bristol Myers Squibb will work to enable availability and affordability of this potential treatment to patients globally.

In May, BMS and Agenus Inc. entered into a definitive agreement under which Bristol Myers Squibb was granted a global exclusive license to Agenus’ proprietary bispecific antibody program, AGEN1777, that blocks TIGIT and a second undisclosed target. AGEN1777 is an Fc-enhanced antibody in late preclinical development designed to target major inhibitory receptors expressed on T and NK cells to improve anti-tumor activity. In preclinical studies this approach has shown significant potential in tumor models where anti-PD-1 or anti-TIGIT monospecific antibodies alone are ineffective. 

Under the agreement, Bristol Myers Squibb will become solely responsible for the development and any subsequent commercialization of AGEN1777 and its related products worldwide. Agenus received a $200 million upfront payment and is eligible for up to $1.36 billion in development, regulatory, and commercial milestones in addition to tiered double-digit royalties on net product sales. Agenus will retain options to conduct clinical studies under the development plan, to conduct combination studies with certain other Agenus pipeline assets, and also, upon commercialization, to co-promote AGEN1777 in the United States.

In June, BMS and Eisai Co. announced an exclusive global strategic collaboration agreement for the co-development and co-commercialization of MORAb-202, an antibody drug conjugate. MORAb-202 is Eisai’s first ADC and combines Eisai’s in house developed anti-folate receptor alpha (FRα) antibody, and Eisai’s anticancer agent eribulin, using an enzyme cleavable linker. It is a potential best-in-class FRα ADC with a favorable pharmacology profile and demonstrated single agent activity in patients with advanced solid tumors. Eisai is investigating MORAb-202 in FRα-positive solid tumors (inclusive of endometrial, ovarian, lung, and breast cancers) in two studies: a Phase I clinical study in Japan and a Phase I/II clinical study in the United States. The companies are planning to move into the registrational stage of development for this asset as early as 2022.

Eisai and Bristol Myers Squibb will jointly develop and commercialize MORAb-202 in the following collaboration territories: Japan; China; countries in the Asia-Pacific region; the United States; Canada; Europe, including the European Union and the United Kingdom; and Russia. Bristol Myers Squibb will be solely responsible for developing and commercializing the drug in regions outside of the collaboration territories. Eisai will remain responsible for the manufacturing and supply of MORAb-202 globally.

Under the financial terms of the agreement, Bristol Myers Squibb will pay $650 million to Eisai, including $200 million as payment toward Eisai research and development expenses. Eisai is also entitled to receive up to $2.45 billion in potential future development, regulatory, and commercial milestones. The parties will share profits, research and development, and commercialization costs in the collaboration territories and Bristol Myers Squibb will pay Eisai a royalty on sales outside of the collaboration territories. Eisai is expected to book sales of MORAb-202 in Japan, China, countries in the Asia-Pacific region, Europe, and Russia. Bristol Myers Squibb is expected to book sales of MORAb-202 in the United States and Canada.

Product Performance

The top revenue generator during 2020 for Bristol Myers Squibb was the multiple myeloma drug Revlimid, acquired in the Celgene transaction. In its first full year under the BMS banner, Revlimid generated $12.11 billion in sales, good enough for third among all prescription products worldwide and second among oncology drugs. In the first half of 2021, sales of Revlimid grew 6 percent to $6.15 billion.

The cardiovascular drug Eliquis generated $9.17 billion in sales for BMS in 2020, an improvement of 15.6 percent over the previous year and No. 4 among all prescription products worldwide. According to company leaders, this was due to higher demand partially offset by lower average net selling prices in both the United States and internationally. In the first half of 2021 sales of Eliquis rose another 18.2 percent to $5.68 billion. 

The immuno-oncologic Opdivo brought in $6.99 billion in sales for BMS in 2020, down 2.9 percent from the previous year. According to company leaders, U.S. sales declined by 9 percent due to lower demand caused by declining second-line eligibility across tumor indications, increased competition for adjuvant melanoma, and lower demand due to COVID-19, partially offset by higher demand due to the launch of the Opdivo plus Yervoy combination for NSCLC and continued growth in RCC. International sales of Opdivo increased by 7 percent due to higher demand as a result of additional indication launches in new countries. In the first half of 2021 sales of Opdivo rose by 6.2 percent to $3.63 billion. 

In February, FDA approved Opdivo in combination with Cabometyx for the first-line treatment of patients with advanced renal cell carcinoma. The approval was based on the Phase III CheckMate -9ER trial, which compared Opdivo in combination with Cabometyx versus sunitinib in patients with advanced RCC. The European Commission approved Opdivo and Cabometyx for a similar indication in April.

In the CheckMate -9ER trial, the primary endpoint was progression-free survival assessed by Blinded Independent Central Review, and the secondary endpoints included overall survival and BICR-assessed objective response rate. In the trial, patients treated with Opdivo in combination with Cabometyx lived twice as long without their tumors progressing as patients who were treated with sunitinib (median PFS was 16.6 months versus median PFS of 8.3 months). Opdivo in combination with Cabometyx also reduced the risk of death by 40 percent compared to sunitinib (median OS was not reached for Opdivo in combination with Cabometyx and not available for sunitinib).

During April, FDA approved Opdivo in combination with fluoropyrimidine- and platinum-containing chemotherapy for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, regardless of PD-L1 expression status. The approval was based on the Phase III CheckMate -649 trial evaluating Opdivo in combination with mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin), compared to chemotherapy (mFOLFOX6 or CapeOX) alone.

In the clinical trial of this patient population, Opdivo plus chemotherapy demonstrated superior overall survival compared to chemotherapy alone, both in all randomized patients, as well as in patients with PD-L1 combined positive score ≥ 5. In an exploratory analysis of all patients, 55 percent of patients on Opdivo in combination with chemotherapy were alive at one year versus 48 percent of patients on chemotherapy alone. The combination also significantly reduced the risk of disease progression or death compared to chemotherapy alone.

That same month, BMS announced results from the CheckMate -816 study, which showed that neoadjuvant treatment with three cycles of Opdivo plus chemotherapy significantly improved pathologic complete response (pCR), a primary endpoint, compared to chemotherapy alone in patients with resectable stage Ib to IIIa non-small cell lung cancer (NSCLC). 

In the study, 24 percent of patients treated with Opdivo plus chemotherapy prior to surgery achieved pCR, compared to 2.2 percent of patients treated with chemotherapy alone, with pCR defined as no evidence of cancer cells in their resected tissue as assessed by a blinded independent pathology review. Additionally, Opdivo plus chemotherapy was well tolerated and showed consistent improvements in pCR regardless of PD-L1 expression levels, histologies or stages of disease. CheckMate -816 represents the first randomized Phase III study to show a significant improvement in pathological response with a neoadjuvant immunotherapy combination in patients with resectable NSCLC.

In May, FDA approved Opdivo for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy. The approval was based on results from the Phase III CheckMate -577 trial that evaluated Opdivo compared to placebo in esophageal or GEJ cancer patients with residual pathologic disease following neoadjuvant CRT and complete resection. The EC subsequently approved a similar indication in August.

In the trial, among patients who received Opdivo, median disease-free survival was twice as long as in those who received placebo (22.4 months compared to 11.0 months). Opdivo reduced the risk of disease recurrence or death by 31 percent compared to placebo. In an exploratory analysis, among patients with adenocarcinoma, mDFS was 19.4 months with Opdivo versus 11.1 months with placebo, and among squamous cell carcinoma patients, mDFS was 29.7 months with Opdivo versus 11 months with placebo.

Also in May, BMS announced new six-and-a-half-year data from CheckMate -067, a randomized, double-blind, Phase III clinical trial, demonstrating durable improvement in survival with first-line Opdivo plus Yervoy therapy and Opdivo monotherapy, versus Yervoy alone, in patients with advanced melanoma. With a minimum follow-up of 6.5 years, median overall survival was 72.1 months with Opdivo plus Yervoy, the longest reported median OS in a Phase III advanced melanoma trial, 36.9 months with Opdivo and 19.9 months with the Yervoy group. In addition, the Opdivo plus Yervoy combination demonstrated a 6.5-year progression-free survival rate of 34 percent (median of 11.5 months) while PFS rates were 29 percent (median of 6.9 months) and 7 percent (median of 2.9 months) for Opdivo alone and Yervoy alone, respectively. Of the 49 percent of patients alive and in follow-up, 77 percent of patients who received the combination, 69 percent of Opdivo-treated patients, and 43 percent of Yervoy-treated patients have been off treatment and never received subsequent systemic therapy.

That same month, BMS announced that Opdivo plus Yervoy with two cycles of chemotherapy showed a durable survival benefit compared to four cycles of chemotherapy alone after two years of follow-up in previously untreated patients with advanced non-small cell lung cancer. 

In the Phase III CheckMate -9LA trial, 38 percent of patients who received Opdivo plus Yervoy with two cycles of chemotherapy were alive at two years, compared to 26 percent of those who received chemotherapy alone. With additional follow-up, median overall survival – the trial’s primary endpoint – was 15.8 months with the dual immunotherapy combination versus 11.0 months with chemotherapy alone.

Also in May, BMS announced that Part 1 of the Phase III CheckMate -227 trial continued to demonstrate the long-term survival benefits of first-line treatment with Opdivo plus Yervoy compared to chemotherapy in patients with advanced non-small cell lung cancer, regardless of PD-L1 expression level or histology, with a minimum follow-up of over four years (49.4 months). In the primary population of patients with PD-L1 expression ≥1%, the four-year survival rate for Opdivo plus Yervoy was 29 percent, compared to 18 percent for chemotherapy.

In an exploratory analysis of patients with PD-L1 expression <1%, more than twice as many patients treated with Opdivo plus Yervoy were alive at four years compared to chemotherapy (24 percent versus 10 percent, respectively).

In June, the European Commission approved Opdivo plus Yervoy for the treatment of adult patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) after prior fluoropyrimidine-based combination chemotherapy. The EC’s decision was based on results from the Phase II CheckMate -142 trial in which Opdivo plus Yervoy demonstrated a clinically meaningful improvement in objective response rate in patients with MSI-H/dMMR mCRC who received prior treatment with fluoropyridine, oxaliplatin and irinotecan. The combination of Opdivo plus Yervoy is the first approved dual immunotherapy treatment option for any GI tumor in the European Union.

Also in June, BMS announced results from the Phase III CheckMate -648 trial, in which two Opdivo-based treatment combinations – Opdivo plus chemotherapy and Opdivo plus Yervoy – demonstrated a statistically significant and clinically meaningful overall survival benefit compared to chemotherapy at the pre-specified interim analysis in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma with tumor cell PD-L1 expression ≥1%, as well as in the all-randomized population. Opdivo plus Yervoy is the first dual immunotherapy combination to demonstrate a superior survival benefit versus chemotherapy in this setting.

For the combination of Opdivo plus chemotherapy, median OS was 15.4 months versus 9.1 months for chemotherapy in patients whose tumors express PD-L1, a primary endpoint, and 13.2 months versus 10.7 months in the all-randomized patient population, a secondary endpoint. A statistically significant progression-free survival benefit was also observed with Opdivo plus chemotherapy in patients whose tumors express PD-L1, with a median PFS by blinded independent central review of 6.9 months compared to 4.4 months with chemotherapy alone.

For the combination of Opdivo plus Yervoy, median OS was 13.7 months versus 9.1 months for chemotherapy in patients whose tumors express PD-L1, a primary endpoint, and 12.8 months versus 10.7 months, respectively, in the all-randomized patient population, a secondary endpoint. Opdivo plus Yervoy did not meet its other primary endpoint of PFS by BICR in patients whose tumors express PD-L1 (4.0 months vs. 4.4 months).

In July, BMS decided to voluntarily withdraw the indication for Opdivo as a single agent for patients with hepatocellular carcinoma who were previously treated with sorafenib from the U.S. market. This action was taken following FDA’s industry-wide evaluation of accelerated approvals for checkpoint inhibitors that have not met their post-marketing requirements demonstrating confirmatory benefit. This included a meeting of the Oncologic Drugs Advisory Committee in April and subsequent discussion with FDA.

Opdivo was first granted this indication in 2017 under FDA’s accelerated approval program, making it the first immunotherapy agent to be approved for use in this setting. The accelerated approval was based on tumor responses from the Phase I/II CheckMate -040 trial. CheckMate -459, the confirmatory randomized study of Opdivo versus sorafenib in the first-line setting, did not achieve statistical significance for its primary endpoint of overall survival per the pre-specified analysis.

Also in July, BMS announced an update on the Phase III CheckMate -651 trial comparing Opdivo plus Yervoy to the EXTREME regimen (cetuximab, cisplatin/carboplatin, and fluorouracil) as a first-line treatment in platinum-eligible patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Although Opdivo plus Yervoy showed a clear, positive trend towards overall survival in patients whose tumors express PD-L1 with a combined positive score (CPS) ≥ 20, the study did not meet its primary endpoints.

In August, FDA approved Opdivo 240 mg every two weeks or 480 mg every four weeks (injection for intravenous use) for the adjuvant treatment of patients with urothelial carcinoma who are at high risk of recurrence after undergoing radical resection, regardless of prior neoadjuvant chemotherapy, nodal involvement or PD-L1 status. The approval was based on the Phase III CheckMate -274 trial, which compared Opdivo 240 mg to placebo. This application was approved under FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible.

In the trial, among patients who received Opdivo, median disease-free survival was nearly twice as long as in those who received placebo (20.8 months versus 10.8 months). Opdivo reduced the risk of disease recurrence or death by 30 percent compared to placebo. Among patients whose tumors express PD-L1 ≥1%, median DFS was not reached for those who received Opdivo versus 8.4 months for placebo; Opdivo reduced the risk of disease recurrence or death by 45 percent.

In September, BMS announced three-year data from the CheckMate -743 trial that demonstrated a durable survival benefit with first-line treatment with Opdivo plus Yervoy compared to platinum-based standard-of-care chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM), regardless of histology. The European Commission approved Opdivo plus Yervoy for this indication in June. With a minimum follow-up of three years (35.5 months), among patients treated with Opdivo plus Yervoy, 23 percent were alive at three years, compared to 15 percent of patients treated with chemotherapy. Treatment with the dual immunotherapy combination continued to show a reduction in the risk of death, and improvement in median overall survival, the trial’s primary endpoint, versus chemotherapy (18.1 months versus 14.1 months, respectively).

The autoimmune product Orencia brought in $3.16 billion in sales for BMS in 2020, up 6 percent compared with 2019. According to company executives this was due to higher demand in the United States and internationally. In the first half of 2021, sales of Orencia were up another 7.4 percent to $1.57 billion. 

During August, FDA accepted BMS’ supplemental Biologics License Application for Orencia for the prevention of moderate to severe acute graft versus host disease (aGvHD) in patients 6 years of age and older receiving unrelated donor hematopoietic stem cell transplantation (HSCT). FDA granted the application Priority Review.

The sBLA submitted to FDA was based on results from the Phase II ABA2 trial and a registry trial based on real world evidence. The ABA2 trial assessed the impact of Orencia on the prevention of severe aGvHD, when added to a standard GvHD prophylactic regimen administered to patients with hematologic malignancies receiving a stem cell transplant from an unrelated, HLA-matched or mismatched donor. A mismatch in HLA increases the risk of GvHD. Results from ABA2 showed that treatment with Orencia resulted in a significant reduction in severe aGvHD and associated morbidity without an increase in disease relapse. The findings of the real-world analysis were consistent with those of ABA2.

In its first full year with BMS, the multiple myeloma product Pomalyst/Imnovid generated $3.07 billion in sales for the company. In the first half of 2021, Pomalyst/Imnovid sales rose 11.6 percent to $1.63 billion.

The oncologic drug Yervoy brought in $1.68 billion in sales for BMS in 2020, an improvement of 13 percent. According to company leaders, this was due to the launch of the Opdivo plus Yervoy combination for NSCLC in the United States and approvals for additional indications internationally. In the first half of 2021 sales of Yervoy rose another 26.3 percent to $966 million.

In The Pipeline

During February, FDA approved Breyanzi (lisocabtagene maraleucel; liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.

The FDA approval of Breyanzi was based on data from the TRANSCEND NHL 001 (017001) trial in which 268 patients with R/R LBCL received Breyanzi, the largest pivotal trial in third-line plus R/R LBCL that included patients with a broad range of histologies and high-risk disease. In the study, 192 patients were treated with Breyanzi at the dose of 50 to 110 x 106 CAR-positive viable T cells and evaluated for efficacy. Of these patients, 73 percent achieved a response, including 54 percent who had minimal or no detectable lymphoma remaining following treatment and 19 percent who achieved a partial response. Median duration of response was 16.7 months in all responders, and for patients who achieved a CR, median duration of response was not reached; for patients with a best response of PR, median duration of response was 1.4 months. Of 104 patients treated with Breyanzi who achieved a best overall response of CR, 65 percent had remission lasting at least six months and 62 percent had remission lasting at least nine months.

Also in February, the European Commission granted full Marketing Authorization for Inrebic (fedratinib) for the treatment of disease-related splenomegaly (enlarged spleen) or symptoms in adult patients with primary myelofibrosis, post-polycythaemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis, who are Janus Associated Kinase inhibitor naïve or have been treated with ruxolitinib. Inrebic is the first, once-daily oral therapy to significantly reduce spleen volume and symptom burden for patients with myelofibrosis where treatment with ruxolitinib has failed, who are intolerant to ruxolitinib or who are JAK inhibitor naïve. 

The EC approval of Inrebic was based on results from the JAKARTA and JAKARTA2 studies, which included patients from 14 countries in the EU. The pivotal JAKARTA study evaluated the efficacy of once-daily oral doses of Inrebic compared with placebo in 289 patients with intermediate-2 or high-risk primary or secondary myelofibrosis with splenomegaly. The JAKARTA2 study evaluated the efficacy of once-daily oral doses of Inrebic in 97 patients with intermediate or high-risk primary or secondary myelofibrosis with splenomegaly previously treated with ruxolitinib. 

In March, FDA approved Abecma (idecabtagene vicleucel; ide-cel) as the first B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Developed jointly by BMS and bluebird bio Inc., Abecma is a personalized immune cell therapy approved as a one-time infusion with a recommended dose range of 300 to 460 x 106 CAR-positive T cells. As an anti-BCMA CAR T cell therapy, Abecma recognizes and binds to BCMA, a protein that is nearly universally expressed on cancer cells in multiple myeloma, leading to the death of BCMA-expressing cells. The European Commission subsequently granted conditional authorization for Abecma in August.

The FDA approval of Abecma was based on data from the pivotal Phase II KarMMa trial of 127 patients with relapsed or refractory multiple myeloma who had received at least three prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. The efficacy evaluable population consists of 100 patients who received Abecma within the dose range of 300 to 460 x 106 CAR-positive T cells. Of these patients, 88 percent received four or more prior lines of therapy and 85 percent were triple-class refractory.

In the study, the overall response rate for the efficacy evaluable population was 72 percent, and 28 percent of patients achieved a stringent complete response. Responses were rapid and durable, with a median time to response of 30 days and median duration of response of 11 months for all responders and 19 months for those who achieved sCR. Of the 28 patients who achieved sCR, an estimated 65 percent had remission lasting at least 12 months.

In April, BMS announced positive results from two pivotal Phase III trials evaluating deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, for the treatment of patients with moderate-to-severe plaque psoriasis. 

The POETYK PSO-1 and POETYK PSO-2 trials, which evaluated deucravacitinib 6 mg once daily, met both co-primary endpoints versus placebo, with significantly more patients achieving Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment score of clear or almost clear (sPGA 0/1) after 16 weeks of treatment with deucravacitinib. Deucravacitinib showed superior skin clearance compared with Otezla for key secondary endpoints in both studies, as measured by PASI 75 and sPGA 0/1 responses at Week 16 and Week 24. At Week 16, 58.7 percent and 53.6 percent of patients receiving deucravacitinib achieved PASI 75 response, respectively, versus 12.7 percent and 9.4 percent receiving placebo and 35.1 percent and 40.2 percent receiving Otezla. At Week 24, 69.0 percent and 59.3 percent of patients receiving deucravacitinib achieved PASI 75 response, respectively, versus 38.1 percent and 37.8 percent receiving Otezla. Among patients who achieved PASI 75 response at Week 24 with deucravacitinib and continued treatment with deucravacitinib, 82.5 percent and 81.4 percent, respectively, maintained PASI 75 response at Week 52.

At Week 16, 53.6 percent and 50.3 percent of patients receiving deucravacitinib achieved sPGA 0/1 response, respectively, versus 7.2 percent and 8.6 percent receiving placebo and 32.1 percent and 34.3 percent receiving Otezla. At Week 24, 58.4 percent and 50.4 percent of patients receiving deucravacitinib achieved sPGA 0/1 response, respectively, versus 31.0 percent and 29.5 percent receiving Otezla.

In May, FDA approved Zeposia (ozanimod) 0.92 mg for the treatment of adults with moderately to severely active ulcerative colitis (UC), a chronic inflammatory bowel disease. Zeposia, an oral medication taken once daily, is the first sphingosine 1-phosphate receptor modulator approved for patients with moderately to severely active UC. The mechanism by which Zeposia exerts therapeutic effects in UC is unknown but may involve the reduction of lymphocyte migration into the intestines. It is thought that by targeting S1P receptors on lymphocytes, a type of immune system cell, Zeposia reduces the number of lymphocytes in peripheral blood.

The approval was based on data from True North, a pivotal Phase III trial evaluating Zeposia as an induction and maintenance therapy versus placebo in adult patients with moderately to severely active UC. 

During induction at Week 10 the trial met its primary endpoint of clinical remission (18 percent versus 6 percent) as well as key secondary endpoints, including clinical response (48 percent versus 26 percent), endoscopic improvement (27 percent versus 12 percent) and endoscopic-histologic mucosal improvement (13 percent versus 4 percent) for Zeposia versus placebo, respectively. During maintenance at Week 52 the trial met its primary endpoint of clinical remission (37 percent versus 19 percent) as well as key secondary endpoints, including clinical response (60 percent versus 41 percent), endoscopic improvement (46 percent versus 26 percent), corticosteroid-free clinical remission (32 percent versus 17 percent) and endoscopic-histologic mucosal improvement (30 percent versus 14 percent) for Zeposia versus placebo, respectively. Decreases in rectal bleeding and stool frequency subscores were observed as early as Week 2 (i.e., 1 week after completing the required 7-day dosage titration) in patients treated with Zeposia.

Also in May, BMS announced results from the Phase II/III RELATIVITY-047 trial, which showed that the fixed-dose combination of relatlimab, a LAG-3-blocking antibody, and Opdivo, administered as a single infusion, demonstrated a statistically significant and clinically meaningful progression-free survival benefit compared to Opdivo alone in patients with previously untreated metastatic or unresectable melanoma. 

This is the first regimen to demonstrate a statistical benefit over anti-PD-1 monotherapy in metastatic melanoma. Among patients treated with the combination, the median PFS was significantly longer at 10.12 months versus 4.63 in those who received Opdivo. The PFS benefit of the fixed-dose combination was observed early, at the time of the first scan, and was consistent over time. In exploratory, descriptive analyses, the combination of relatlimab and Opdivo extended PFS regardless of pre-specified subgroups and stratification factors.

That same month, BMS announced a new analysis of data from the Phase III EXPLORER-HCM study evaluating mavacamten, an investigational, first-in-class cardiac myosin inhibitor, in patients with obstructive hypertrophic cardiomyopathy. At 30 weeks, the change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ OSS) was greater in mavacamten patients than placebo, with similar benefits across all KCCQ subscales. Moreover, a greater proportion of mavacamten patients achieved a very large, clinically meaningful improvement (≥20 points) in the KCCQ OSS, compared to placebo, 36 percent versus 15 percent. FDA accepted a New Drug Application for mavacamten in March.

In June, the European Commission granted full Marketing Authorization for Onureg (azacitidine tablets) as a maintenance therapy in adult patients with acute myeloid leukemia who achieved complete remission or complete remission with incomplete blood count recovery following induction therapy with or without consolidation treatment and who are not candidates for, including those who choose not to proceed to, hematopoietic stem cell transplantation (HSCT). Onureg is the first once-daily, frontline oral maintenance therapy to demonstrate significant overall survival and show a relapse-free survival benefit in patients with a broad range of AML subtypes.

The EC approval of Onureg was based on results from the QUAZAR AML-001 study, a Phase III, international, randomized, double-blind trial. Eligible patients were ages 55 years or older, had newly diagnosed AML, intermediate or poor cytogenetics, had achieved first CR or CRi following intensive induction chemotherapy with or without consolidation treatment (per investigator preference prior to study entry), and were not candidates for HSCT at the time of screening.

Median OS, the primary endpoint, from time of randomization was greater than two years (24.7 months) in the Onureg arm compared to 14.8 months for placebo. The median duration of treatment was 12 cycles (1 to 82) for Onureg and 6 cycles with placebo (1 to 76). Median relapse-free survival was also significantly longer with Onureg than with placebo (10.2 months and 4.8 months, respectively). Overall health-related quality of life was preserved during Onureg treatment.

Also in June, BMS and Acceleron Pharma Inc. announced the first data from the Phase II BEYOND study evaluating Reblozyl (luspatercept-aamt), a first-in-class erythroid maturation agent, plus best supportive care in adult patients with non-transfusion dependent beta thalassemia. Results demonstrated that 77.7 percent of patients treated with Reblozyl achieved a hemoglobin increase (≥1.0 gram/deciliter) compared to 0 percent of patients in the placebo arm. Changes in patient-reported outcomes also correlated with increases in hemoglobin. NTD beta thalassemia is a term used to describe patients who do not require lifelong regular red blood cell transfusions for survival, although they may require occasional or even frequent transfusions, usually for defined periods of time. Reblozyl is the first erythroid maturation agent approved in the European Union, United States, and Canada to address anemia-associated beta thalassemia and lower-risk myelodysplastic syndromes, representing an important class of therapy for eligible patients.

Also in June, BMS announced positive topline results from TRANSFORM, a global, randomized, multicenter Phase III study evaluating Breyanzi as a second-line treatment in adults with relapsed or refractory large B-cell lymphoma compared to salvage therapy followed by high-dose chemotherapy and hematopoietic stem cell transplant, which is currently considered a gold standard treatment for these patients. 

Results of a pre-specified interim analysis conducted by an independent review committee showed the study met its primary endpoint of demonstrating a clinically meaningful and highly statistically significant improvement in event-free survival, as well as key secondary endpoints of complete response rate and progression-free survival compared to standard of care. 

Overall survival data were immature at the time of this interim analysis. The results represent the first time a therapy has shown a benefit over standard of care high-dose chemotherapy and stem cell transplant in relapsed or refractory LBCL, and the first time a CD19-directed CAR T cell therapy has demonstrated potential as a second-line therapy in this patient population.