Susan Haigney

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FDA announced on May 28, 2024 that it has approved Bkemv (eculizumab-aeeb) as the first interchangeable biosimilar to Soliris (eculizumab) for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis and atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy.

PNH and aHUS involve the breakdown of red blood cells. PNH causes anemia, thrombosis, pancytopenia, and dark urine. Anemia is also found in aHUS as well as thrombocytopenia and kidney failure.PNH and aHUS are considered rare diseases. A rare disease, according to FDA (1), impacts fewer than 200,000 people in the United States.

Bkemv, a monoclonal antibody, binds to the complement C5 protein, inhibiting activation of the complement system (a part of the human immune system). The breakdown of red blood cells in the bloodstream is prevented by the binding in PNH and aHUS patients. Bkemv, which is the 53rd FDA-approved biosimilar in the US, is only available through a restricted program—Bkemv Risk Evaluation and Mitigation Strategy.

Labeling for Bkemv includes a Boxed Warning that it increases the risk of serious and life-threatening meningococcal infections caused by 

 Therefore, FDA states that patients should complete meningococcal vaccination before starting Bkemv or Soliris. Patients should also be monitored for symptoms of meningococcal infections (1).

“As an interchangeable biosimilar, Bkemv is highly similar with no clinically meaningful differences to Soliris. Bkemv has the same safety warnings and is expected to have the same adverse reactions as Soliris,” FDA stated in the press release. “The most frequently reported adverse reactions in the PNH randomized trial for Soliris (≥10% overall and greater than placebo) are headache, nasopharyngitis (common cold), back pain and nausea. The most frequently reported adverse reactions in aHUS single arm prospective trials for Soliris (≥20%) are headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, swelling of lower legs or hands, nausea, urinary tract infections, and fever.”

“Many rare conditions are life-threatening, and many do not have treatments,” said Sarah Yim, director of the Office of Therapeutic Biologics and Biosimilars in FDA’s Center for Drug Evaluation and Research, in a press release (1). “The FDA is committed to help facilitate the development of safe and effective interchangeable biosimilar treatments that can expand access for individuals with rare diseases whose current treatment options are limited.”

Henlius’ HERCESSI (HLX002; trastuzumab-strf), for adjuvant treatment of HER2-overexpressing breast cancer, HER2-overexpressing metastatic breast cancer, and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.

“Our patient-centered approach has led us to unwaveringly explore high-quality, effective, affordable, and accessible treatment options, and our determination to promote HLX02 in more than 40 markets around the world is Henlius' response to patients' concerns,” said Jason Zhu, executive director, chief executive officer and chief financial officer of Henlius, in a press release (2). “We look forward to reaching more patients in North America and providing them with more cost-effective access to high-quality biologics.”

FDA. FDA Approves First Interchangeable Biosimilar for Two Rare Diseases. Press Release. 

Henlius. Henlius Trastuzumab Receives FDA Approval in the United States. Press Release. April 26, 2024.

Articles

Bkemv (eculizumab-aeeb) is the first interchangeable biosimilar to Soliris (eculizumab) to treat paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

FDA Approves Interchangeable Biosimilar to Soliris

Integrated Biosciences, a biotechnology company that uses synthetic biology and machine learning to develop next-generation therapeutics for age-related diseases, announced on May 28, 2024, that it is collaborating with Illumina Ventures Labs to create novel therapeutics targeting the transcriptome. Integrated Biosciences will integrate the company’s drug discovery engine with Illumina sequencing.

Integrated Biosciences, which is developing a portfolio of preclinical-stage assets to treat multiple age-related diseases, stated in a press release that the partnership “will generate additional therapeutic assets and new discovery platforms that hold the promise of reshaping drug discovery” (1). The partnership will include monetary and scientific support and allow Integrated Biosciences to discover and design new classes of small-molecule therapeutics that shape the transcriptomes and methylomes of cell populations. The company plans for these drug candidates to be applicable to diseases where cell state and identity are important, including diseases related to aging and development.

“All drugs act by modifying cellular components, and nucleic acids are particularly important. This partnership is a nexus to using small molecules to systematically target RNA expression and DNA modifications across cell types, such that we can control exactly how cells behave,” said Felix Wong, PhD, co-founder of Integrated Biosciences, in the press release (1). “We will generate unprecedented large-scale datasets that provide maps of cell states and how to alter them, charting the course for definitive cures for age-related diseases.”

“Illumina Ventures supports innovative companies that are pursuing breakthrough science, and our partnership with Integrated Biosciences, through our Illumina Ventures Labs, represents an investment in the intersection of healthcare, genomics, and sequencing,” said Ron Mazumder, PhD, partner at Illumina Ventures, in the release. “Integrated Biosciences is an outlier early stage company that has already pioneered breakthroughs in drug discovery. Illumina Ventures is convinced that, with our unique support and resources, Integrated Biosciences will unlock novel therapeutic candidates and modalities that bring next-generation sequencing to the forefront of drug discovery.”

In December 2023, Integrated Biosciences announced a new class of small-molecule antibiotics discovered leveraging an artificial intelligence (AI)-powered platform (2). Researchers at the Massachusetts Institute of Technology (MIT), the Broad Institute of MIT and Harvard, the Wyss Institute for Biologically Inspired Engineering, and the Leibniz Institute of Polymer Research in Dresden, Germany, collaborated on the study, which screened more than 12 million candidate compounds.

“This discovery of a new class of antibiotics is a breakthrough result showing that artificial intelligence and explainable deep learning are uniquely capable of catalyzing drug discovery,” said Wong (2). “Our work makes publicly available several high-powered models to accurately predict both antibiotic activity and toxicity. Importantly, this is one of the first demonstrations that deep learning models can explain what they are predicting, with immediate and far-reaching implications to how drug discovery is done and how efficiently we can find new drugs using AI.”

“An important implication of this study is that deep learning models in drug discovery can, and in many cases should, be made explainable. While AI continues to make an impact, it is also limited by the many black box models that are commonly used and obfuscate the underlying decision-making process. By opening up these black boxes, we aim to create more generalizable insights that may be more useful in accelerating the use and development of next-generation approaches to drug discovery,” said Satotaka Omori, PhD, founding member and Head of Aging Biology at Integrated Biosciences (2).

Integrated Biosciences. Integrated Biosciences Collaborate with Illumina Ventures Labs to Design Novel Therapeutics Targeting the Transcriptome. Press Release. May 28, 2024.

Integrated Biosciences. Integrated Biosciences Announces Nature Publication Identifying New Class of Antibiotics Discovered Via Company’s AI-Powered Platform. Press Release. 

The partnership will create therapeutic assets and new discovery platforms and potentially reshape drug discovery.

Integrated Biosciences Collaborates with Illumina Ventures Labs Collaborate on Novel Therapeutics

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Hospira, a Pfizer company, announced on May 21, 2024 that it was voluntarily recalling the lots listed in the table below of Buprenorphine Hydrochloride Injection Carpuject Units and Labetalol Hydrochloride Injection, USP Carpuject Units because of incomplete crimp seals. The company also received a customer complaint of a leaking unit.

The recalled lots were distributed nationwide to wholesalers/hospitals in the United States from September 2023 through April 2024. The National Drug Code (NDC), lot number, expiration date, and configuration details for the recalled lots are as follows:

Buprenorphine Hydrochloride Injection–CIII, Carpuject Single-dose Cartridge/Tube Unit with Luer Lock. NDC: Carton 0409-2012-32, Cartridge 0409-2012-03; lot number HJ3965, expiration date 2024/09; lot number HJ8546, expiration date 2024/10. Both have a concentration of 0.3 mg base/mL and are 10 cartridge units/carton.

Labetalol Hydrochloride Injection, USP Carpuject Single-dose Cartridge Unit with Luer Lock. NDC: Bundle 0409-2339-34, Carton/Cartridge 0409-2339-24; lot number HJ7566, expiration date 2025/05; lot number HN8747, expiration 2025/09; HN8749 expiration date 2025/09. Both have a concentration of 20 mg/4 mL (5 mg/mL) and are 10 carton/ cartridge units/bundle. 

While Pfizer has not received any related reports of adverse events, if an impacted product is administered, there is an increased risk for lack of efficacy and systemic infection that might require additional treatment, according to the company. Adverse events may be reported to FDA through the agency’s MedWatch program.

“Pfizer places the utmost emphasis on patient safety and product quality at every step in the manufacturing and supply chain process. Pfizer has notified direct consignees by letter to arrange for the return of any recalled product,” the company stated in a press release (1).

Buprenorphine HCl Injection, a clear, sterile, injectable agonist-antagonist analgesic intended for intravenous or intramuscular administration, is used to manage pain for which alternate treatments are inadequate. Labetalol HCl Injection is a treatment for controlling blood pressure in severe hypertension.

In December 2023, the company had another voluntary recall. That recall was of lots of 4.2% Sodium Bicarbonate Injection, USP ABBOJECT Glass Syringe, 5 mEq/10 mL; 8.4% Sodium Bicarbonate Injection, USP Lifeshield ABBOJECT Glass Syringe, 50 mEq/50 mL; and Atropine Sulfate Injection, USP Lifeshield ABBOJECT Glass Syringe, 1 mg/10 mL because of the presence of glass particulate matter found during product inspection (2).

“Potential complications related to injection of visible and subvisible inert particles include inflammation of a vein, granuloma, and blockage of blood vessels or life-threatening blood clot events. The frequency and severity of these adverse events could vary depending upon a variety of factors including the size and number of particles in the drug product, patient comorbidities (such as age, compromised organ function), and presence or absence of vascular anomalies,” the company stated in the release (2).

Hospira. Hospira Inc. Issues a Voluntary Nationwide Recall for Buprenorphine Hydrochloride Injection CarpujectTM Units and Labetalol Hydrochloride Injection, USP CarpujectTM Units Due to the Potential for Incomplete Crimp Seals.

Hospira. Hospira, Inc. Issues A Voluntary Nationwide Recall For 4.2% Sodium Bicarbonate Injection, 8.4% Sodium Bicarbonate Injection, and Atropine Sulfate Injection Due to the Potential Presence of Glass Particulate Matter. Press Release. 

The units are being recalled because of incomplete crimp seals and one complaint of a leaking unit.

Hospira Recalls Buprenorphine Hydrochloride Injection Carpuject Units and Labetalol Hydrochloride Injection, USP Carpuject Units 

Bristol Myers Squibb (BMS) announced on May 22, 2024 that it is creating a 10-year plan—ASPIRE (Accessibility, Sustainability, Patient-centric, Impact, Responsibility and Equity)—to expand access to its therapies to more than 200,000 patients in low- and middle-income countries (LIMCs) by 2033. The ASPIRE plan will include strategies and the development of access plans to increase affordability and availability of BMS’ medicines in LMICs to ensure 100% of the company’s marketed products are supported by access plans. 

BMS has introduced local brands of their drugs, with the company filing 11 local brands in 2023; five have received regulatory approvals. “BMS local brands are making an impact in countries [such as] Thailand, which has the highest prevalence of beta thalassemia, by providing treatment options [such as] Rojusna to help combat this widespread disease,” the company stated in a press release (1).

Part of the ASPIRE plan is for BMS to collaborate with the Access to Oncology Medicines (ATOM) Coalition to bring its cancer treatment, Opdivo (nivolumab), to Pakistan, Rwanda, Zambia, and other countries. ATOM is led by the Union for International Cancer Control and includes 40 global partners to address the challenges of availability, affordability, and appropriate use of oncology medicines.

“Access to potentially life-saving innovative medicines is very limited in some parts of the world, leaving patients with few treatment options for serious diseases [such as] cancer,” said Christopher Boerner, PhD, board chair and chief executive officer, Bristol Myers Squibb, in the press release. “Bristol Myers Squibb believes patients who can benefit from our medicines should have access to them. Our ASPIRE strategy is an important step toward accelerating and expanding patient access to these much-needed treatments.”

In countries where BMS does not have a commercial presence, the company is making its medicines available through the Direct Import and the Direct-to-Institution (DTI) pathways. BMS is providing 12 medicines using a tiered pricing commensurate to more than 80 LIMCs through the Direct Import pathway. The DTI pathway, which provides safe, broad, and timelier access to BMS medicines through collaboration with local institutions, includes efforts in five LMICs in East Africa and Pakistan and West Africa in 2025. The goal is to include more than 15 LMICs by 2026.

“By investing in solutions that reduce quality-of-care gaps and strengthen health systems, BMS will help drive equitable access to innovative medicines to patients around the world, regardless of where patients live. Enabling timely access to innovative medicines in LMICs is part of BMS’ commitment to health equity globally and our Environmental, Social and Governance (ESG) strategy,” the company stated in the release.

 that it is has established an agreement with Cellares, a US-based integrated development and manufacturing organization specializing in cell therapy manufacturing, to reserve global capacity and supply for manufacturing chimeric antigen receptor T-cell therapies. The deal is valued at up to $380 million in upfront and milestone payments (2). 

Bristol Myers Squibb Announces 10-Year Strategy to Reach More Patients in Low- and Middle-Income Countries.

Bristol Myers Squibb. Bristol Myers Squibb and Cellares Announce a $380M Worldwide Capacity Reservation and Supply Agreement for the Manufacture of CAR T Cell Therapies to Bring the Promise of Cell Therapy to More Patients, Faster. Press Release. April 22, 2024.

The company is collaborating with the Access to Oncology Medicines Coalition to expand patient access to immuno-oncology therapy Opdivo.

Bristol Myers Squibb Plans 10-Year Strategy to Expand Access to Medications

AstraZeneca announced on May 20, 2024 that it is planning a new $1.5 billion antibody drug conjugate (ADC) facility in Singapore. The new facility is supported by the Singapore Economic Development Board (EDB) and will be the company’s first end-to-end ADC production site. ADCs deliver highly potent cancer-killing agents directly to cancer cells and require multiple process steps, including antibody production, drug and linker synthesis, conjugation of the drug-linker to the antibody, and filling of the completed ADC. Among its drug candidates, AstraZeneca has six wholly owned ADCs in the clinic and others in preclinical development.

“AstraZeneca has built an industry-leading portfolio of cancer medicines including antibody drug conjugates which have shown enormous potential to replace traditional chemotherapy for patients across many settings,” said Pascal Soriot, chief executive officer of AstraZeneca, in a press release (1). “Singapore is one of the world’s most attractive countries for investment given its reputation for excellence in complex manufacturing, and I am excited for AstraZeneca to locate our $1.5 billion ADC manufacturing facility in the country.”

"We welcome AstraZeneca's decision to establish a manufacturing presence in Singapore for the first time. It will also be a first for AstraZeneca—an end-to-end manufacturing facility for novel antibody drug conjugates that enables precision therapy for cancer,” said Png Cheong Boon, chairman, EDB, in the release. “This greenfield investment is a strong show of confidence in Singapore's biopharmaceutical manufacturing capabilities and talent, strengthens our ecosystem in supporting the development and manufacturing of precision medicines, and creates meaningful jobs and economic opportunities for Singapore. We look forward to a successful partnership with AstraZeneca."

AstraZeneca will work with the Singapore's government and other partners on sustainability solutions for the new ADC facility. The company plans for the facility to have zero carbon emissions. Construction on the new facility will begin at the end of 2024 with a target of 2029 for full operation.

In an email commenting on AstraZeneca’s Singapore investment (2), 

, managing director and head of European Healthcare at Houlihan Lokey, said:

“With a wide portfolio of in-house [a]ntibody-[d]rug [c]onjugates (ADCs) at various stages of clinical and pre-clinical development, AstraZeneca’s plan to build a new facility by 2029 exemplifies the long-term strategic thinking of large-cap pharmaceutical companies aiming to control their supply chains more effectively. This move reflects the industry's recognition of the complexities and costs associated with developing and manufacturing ADCs, which necessitates substantial investment in infrastructure to ensure quality and efficiency in production.

“The construction of this facility also highlights a broader trend within the pharmaceutical industry, where strategic initiatives are being directed towards high-growth market segments. ADCs, for instance, represent a significant opportunity with an estimated market size of $10 billion, growing at a rate exceeding 15% annually, driven largely by their promising applications in oncology. By investing in dedicated facilities, companies are positioning themselves to capitalize on this rapid growth and technological advancement.

“The strategic significance of ADCs in the pharmaceutical industry is underscored by other recent high-profile acquisitions. 

AbbVie’s $10 billion acquisition of ImmunoGen

 was partly motivated by the latter's expertise in ADCs, particularly in the area of solid tumor oncology. Similarly, 

 for $43 billion significantly bolstered its oncology capabilities, integrating Seagen's pioneering ADC technology.

“These acquisitions illustrate how major pharmaceutical companies are significantly expanding their oncology portfolios and technological capabilities to maintain a competitive edge in the market. AstraZeneca in particular, stands out as a market leader in the increasingly competitive market for ADCs, with the development of the site in Singapore further cementing its position.”

1. AstraZeneca. AstraZeneca Plans $1.5 Billion Manufacturing Facility for Antibody Drug Conjugates (ADCs) in Singapore. Press Release. May 20, 2024.
2. Tomasic, P. Commenting on AstraZeneca Building a $1.5bn Manufacturing Site in Singapore. Email Distributed by Dynevor, S. Houlihan Lokey, May 20, 2024.

The new facility will be the company’s first to offer full manufacturing processing for antibody drug conjugates.

AstraZeneca Plans $1.5 Billion ADCs Facility in Singapore

The European Medicines Agency (EMA) announced on May 17, 2024 that its Pharmacovigilance Risk Assessment Committee (PRAC) has recommended the suspension of medicines that contain 17-hydroxyprogesterone caproate (17-OHPC). Drugs that contain 17-OHPC are used to prevent premature birth or loss of pregnancy. Other authorized uses include treatment of gynecological and fertility disorders.

The recommendation comes after a PRAC review that found there is a possible “but unconfirmed” risk of cancer developing in people that were exposed to 17-OHPC in the womb. The review also found that 17-OHPC is not effective in preventing premature birth and may not be effective in other authorized uses.

“In view of the concern raised by the possible risk of cancer in people exposed to 17-OPHC in the womb, together with the data on the effectiveness of 17-OHPC in its authorized uses, the PRAC considered that the benefits of 17-OHPC do not outweigh its risks in any authorized use. The Committee is therefore recommending the suspension of the marketing authorizations for these medicines. Alternative treatment options are available,” EMA stated in a press release (1).

PRAC will develop direct healthcare professional communication (DHPC) for 17-OPHC medicines that recommends use of alternative treatment options. Once approved, the DHPC will be provided to healthcare professionals by the marketing authorization holder.

Results from a large population-based study that looked at the risk of cancer in those exposed to 17-OHPC in the womb was used to make PRAC’s decision. While data suggested there was an increased risk of cancer compared to people not exposed to these medications, the study had limitations, according to PRAC. “The Committee therefore concluded that the risk of cancer in people exposed to 17-OHPC in the womb is possible but cannot be confirmed due to uncertainties” (2). PRAC also considered effectiveness data of other authorized uses of these medicines in a study of more than 1700 pregnant women with a history of preterm delivery. PRAC found 17-OHPC to be no more effective than placebo in preventing recurrent premature birth or medical complications.

In April 2023, FDA withdrew the approval of Makena (hydroxyprogesterone caproate injection) after post-marketing data found that the drug was not effective and there were risks associated with its use. Makena had been originally approved under FDA’s accelerated approval pathway in 2011 (3).

“It is tragic that the scientific research and medical communities have not yet found a treatment shown to be effective in preventing preterm birth and improving neonatal outcomes—particularly in light of the fact that this serious condition has a disparate impact on communities of color, especially Black women,” said FDA Commissioner Robert M. Califf in a press release at the time of the withdrawal (3). “Fundamentally, however, the touchstone of FDA drug approval is a favorable benefit-risk assessment; without that favorable assessment, the drug should not have the status of being FDA-approved.”

“We acknowledge at the outset the serious problems of preterm birth with respect to both maternal and neonatal health and the contribution of institutional forces that have led to health disparities, including preterm birth, among Black women,” said FDA Chief Scientist Namandjé Bumpus in the release. “Nothing in this opinion today is intended to minimize these concerns—to the contrary, our hope is that this decision will help galvanize further research.”

EMA. Meeting Highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 13-16 May 2024. Press Release. May 17, 2024.

EMA. Hydroxyprogesterone Caproate-containing Medicinal Products–Referral. 

FDA. FDA Commissioner and Chief Scientist Announce Decision to Withdraw Approval of Makena. Press Release. April 6, 2023.

After a review, the agency concluded there was a possible risk of cancer to those exposed to 17-hydroxyprogesterone caproate in the womb.