Overcoming Poor Solubility Through Accelerated Dissolution

Drug Solutions Podcast

The nitrosamines contamination in “sartan” drugs emphasized the importance of risk assessment in API ingredients manufacturing.

What Goes Wrong When API Quality is Compromised?

Adapting to the increasing complexity and poor solubility and bioavailability of molecules in the pipeline.

Adapting to Solubility/Bioavailability Challenges

Addressing key challenges in building commercial-scale mRNA production facilities.

Engineering Challenges in Commercial mRNA Vaccine Manufacturing

Successful digital transformation in biopharma requires an integrated approach to the data lifecycle.

An Integrated Approach to the Data Lifecycle

Automation of pharmaceutical packaging saves costs and time, say contract packagers.

Automating Packaging of Bio/Pharmaceuticals

Development and Scalability of ADCs and CGTs

Drug Digest

B.S Sathya Durga is Director at Acute Market Reports.

India, the home of more than 10,000 pharmaceutical manufacturing sites, is a major player in the global pharmaceutical market. The country manufactures the majority of the world's active ingredients for generic drugs, is the source of more than 90% of the medications used by Americans, and accounts for more than 60% of global vaccine production, according to data from US Pharmacopeia.

Consequently, India has an ambitious vision: to grow its pharma business to a value of $130 billion by 2030. According to a report from 

, the Indian pharmaceutical business was worth $42 billion in 2020 and is set to grow at a compound annual growth rate of 12% from 2020 to 2030. However, while the Indian pharmaceutical industry is the third largest in terms of volume, it ranks at just fourteenth in terms of value.

To enable rapid growth, India must advance its value proposition amidst intense cost pressures and competition. To stimulate the anticipated growth, it is evident that India needs to undergo a significant transition from generic drug producer to a producer of novel molecules and biosimilars through rigorous R&D initiatives.

Modern technologies are critical in facilitating advancement of India’s pharmaceutical manufacturing industry, as they can enable many crucial process improvements:

Virtual product design allows products to be produced, tested, or assessed virtually without physical prototypes, minimizing research time.

Robust tracking systems automatically alter production to reduce logistics failures.

Intelligent sensors and a connected value chain enable data interchange from design to production and supplier/customer integration.

Autonomous robots provide flexible and adaptive production lines for many models and small customized lots, improving performance.

Predictive maintenance links wirelessly to the cloud for big data and analytics, reducing downtime and improving maintenance.

The organizations that are most likely to have a competitive advantage in the Indian pharma manufacturing market are those who continuously adopt new technology, find ways to harness the technology, and promote business integration. Consequently, significant advancement is predicated on modernization of the complete pharmaceutical manufacturing process.

Technology First Approach – The Need of the Hour

Indian pharmaceutical companies are prioritizing technology to maintain and enhance their market position. All new pharma plants must meet standards set by FDA, World Health Organization, and Pharmaceutical Inspection Co-operation Scheme.

Similarly, an increasing number of Indian pharmaceutical companies are deploying cloud computing, as well as technologies like artificial intelligence/machine learning (AI/ML) and robotic process automation (RPA). This allows them to modernize supply chain processes, extract better insights from data, conduct modeling/simulations more quickly, accelerate the drug development process, and save significant time in drug commercialization.

As a result of the COVID-19 pandemic, Indian companies have adapted to the speed of global digital transformation adoption and increased supply chain efficiencies. Information Technology (IT) companies have been offering different subscription models to the pharma industry that best suit their payment structure. For instance, the “pay as you use '' model charges companies based on usage, making it ideal for expenses like utility bills.

Pharma 4.0 allows pharma businesses to leverage the internet of things (IoT), Cognitive Science, AI/ML, blockchain, and RPA in tandem, utilizing the digital cloud as a foundation. This helps pharma companies enhance distribution and supply chain management by accelerating production and reducing errors. Currently, a medium-sized IT company in India enables more than 150 to 200 pharmaceutical companies to modernize the pharma manufacturing process at some level.

Shifting Priorities to Create Smart Factories

The production capabilities of firms need to be increased in order to create more value-based pharma products. Existing operations in India need to be automated and digitized so that the companies can adhere to the appropriate standards and maintain precise control over the product's quality.

The front-end priority has always prevented Indian companies from focusing on shop-floor technologies, but upgrades to these technologies are increasingly becoming more global. The shop floor is undergoing transformation as a result of developments in the IoT, AI/ML algorithms, 3D printing, machine vision, advanced physical robotics, and parametric optimization.

Development of integrated production capabilities would provide Indian businesses, industries, and the country as a whole with a significant and long-lasting competitive advantage. Existing process technologies need to be scaled up for industrial application so that prices can be reduced. For instance, the University of Calicut discovered a promising method of producing penicillin from wasted fruit by using solid state fermentation rather than submerged fermentation technology. If that technologies like this could be enabled on a widespread scale, it could prove critical to widespread process improvements; the pharmaceutical industry in India must evaluate smart factory developments.

The Indian government has been actively partnering with pharma companies and has been allotting considerable funds for the construction of new pharma facilities, pharma research, healthcare schemes, and so on. These initiatives open new doors for the acceptance of technologies to enhance production efficiency like never before.

However, while technologies such as cloud AI are extensively deployed in the U.S. and Europe, in India modernization of pharma manufacturing is still in its infancy. Companies are finding use cases in many commercial operations and manual procedures to eliminate human interaction and improve accuracy.

As the labor costs in India are lower than in other countries, cost sensitivity must be considered a prime factor. Pharma companies are beginning to use AI and ML, but it's still in the proof-of-concept stage. India is only starting to utilize blockchain for transparent data sharing between contractors and suppliers. While skill and labor aren't a significant issue in India, unstable prices and policies impede sector expansion.

With the current pace and ambitions, active government involvement, and strategic collaborations, it is anticipated that in the coming decade India will grow to adopt advanced modernization technologies in the pharma manufacturing segment to be at par with the developed economies.

Articles

Guest contributor B.S. Sathya Durga discusses the importance of modernizing India's pharmaceutical manufacturing industry.

Modernization of India’s Pharma Manufacturing Industry: “Leader” or “Laggard”

FDA’s Center for Drug Evaluation and Research (CDER) Small Business and Industry Assistance (SBIA) is hosting a three half-day virtual conference from August 16–18, 2022. The conference is in collaboration with the Promoting the Quality of Medicines Plus (PQM+) program, which is funded by the US Agency for International Development (USAID) and led by the United States Pharmacopeial Convention (USP).

The event is intended to help National Medicines Regulatory Authorities (NMRA) in low-and-middle income countries (LMICs) gain a better understanding of FDA’s role in international regulatory harmonization, USP and USAID’s PQM+ program’s role in supporting the strengthening of regulatory systems in LMICs, and more. Topics being covered include FDA drug approval pathways and FDA review of drug applications (new and generic drugs), specifically new TB medicines, FDA review of stability testing, bioequivalenceand post-marketing changes, nitrosamines impurities, and more.

Keynote speakers include FDA’s Janet Woodcock, MD, Principal Deputy Commissioner - Office of The Commissioner; USP CEO Ronald T. Piervincenzi, PhD; USAID’s Dr. Atul Gawande, Assistant Administrator for Global Health; WHO’s Tereza Kasaeva, MD, PhD, Director Global TB Programme; and Rogerio Gaspar, PhD Director of Regulation and Prequalification .

The event is virtual, and registration is free.

FDA’s CDER SBIA is hosting a three-day virtual conference regarding regulatory best practices for global access to medicines. 

FDA to Host Multi-Day Global Access Virtual Conference

Pfizer and Global Blood Therapeutics (GBT), a biopharmaceutical company specializing in sickle cell disease (SCD) treatment, announced on Aug. 8, 2022 a definitive agreement under which Pfizer will purchase all outstanding shares of GBT at $68.50 (totaling approximately $5.4 billion). This purchase will grant Pfizer the rights to GBT’s existing Oxbryta (voxelotor) treatment, as well as other treatments in development.

Voxelotor is an oral, once-daily therapy for patients with SCD that increases hemoglobin’s affinity for oxygen. Since oxygenated sickle hemoglobin does not polymerize, voxelator inhibits sickle hemoglobin polymerization and the resultant sickling and destruction of red blood cells that leads to hemolysis and hemolytic anemia. Generating net sales of approximately $195 million in 2021, the treatment is currently approved in the United States, European Union, United Aram Emirates, Oman, and Great Britain.

GBT’s pipeline includes two key treatments that received orphan drug and rare pediatric disease designations from FDA. According to a company press release, if approved, GBT’s SCD treatments could achieve combined worldwide peak sales of more than $3 billion.

GBT021601 (GBT601), an oral, once-daily, next-generation sickle hemoglobin polymerization inhibitor in the Phase II portion of a Phase II/III clinical study. GBT601 is designed to improve both hemolysis and frequency of vaso-occlusive crisis (VOC).

Inclacumab is a fully human monoclonal antibody that targets P-selectin. It is currently being evaluated in two Phase III clinical trials as a quarterly treatment to reduce the frequency of VOCs, as well as the hospital readmission rates resulting from VOCs.

“Sickle cell disease is the most common inherited blood disorder, and it disproportionately affects people of African descent. We are excited to welcome GBT colleagues into Pfizer and to work together to transform the lives of patients, as we have long sought to address the needs of this underserved community,” said Albert Bourla, chairman and CEO, Pfizer, in the release. “The deep market knowledge and scientific and clinical capabilities we have built over three decades in rare hematology will enable us to accelerate innovation for the sickle cell disease community and bring these treatments to patients as quickly as possible.”

“Today is an exciting milestone that accelerates GBT’s mission to discover, develop and deliver life-changing treatments that provide hope to underserved patient communities,” said Ted W. Love, president and CEO, GBT, in the release. “Pfizer will broaden and amplify our impact for patients and further propel much-needed innovation and resources for the care of people with sickle cell disease and other rare diseases, including populations in limited-resource countries. We look forward to working together with Pfizer to serve our communities and advance our shared goal of improving health equity and expanding access to life-changing treatments to create a healthier future for all.”

Pfizer’s $5.4 billion acquisition of Global Blood Therapeutics is expected to strengthen its sickle cell disease portfolio.

Pfizer to Acquire Global Blood Therapeutics for $5.4 Billion

Sartorius announced that it has agreed to purchase Alubmedix through its French-listed subgroup Sartorius Stedim Biotech for £415 million (US$429 million) on Aug. 8, 2022. Albumedix is a provider of recombinant human albumin, which is used in various applications in the biopharmaceutical industry, such as an animal-free additive to cell culture media and for the stabilization of vaccines and viral therapies. The purchase is expected to close before the end of the third quarter of 2022.

According to a company press release, Albumedix will join Sartorius' Bioprocess Solutions Division. Its existing 72,000-ft2 site in Nottingham, UK, will be established as a center of excellence for innovation and good manufacturing practice-compliant production of raw materials.

“Albumedix will be an important addition to Sartorius’ advanced therapy solutions, particularly regarding our cell culture media business, as it will enable us to strengthen our position as a relevant supplier of innovative chemically defined media and critical ancillary materials,” said René Fáber, member of the executive board for the Bioprocess Solutions Division of Sartorius, in the press release. “This market offers high growth potential due to the increasing regulatory requirements as well as rising demand for the use of recombinant human albumin in near-patient applications. Albumedix will also add important formulation excipients to our vaccine production solutions, allowing us to expand our existing customer relationships and forge new ones.”

“We are delighted to be joining forces with Sartorius and look forward to accelerating our ambitious growth plans in delivering critical solutions to our global customers,” said Jonas S. Møller, CEO of Albumedix, in the release. “We have been highly impressed with Sartorius’ knowledge and capabilities in the bioprocessing markets, and we are excited to join this purposeful journey. We believe Sartorius will bring tremendous value in strengthening our market reach and broadening our innovation capacity, as well as significantly scaling up our existing platform.”

Sartorius’ £415 million (US$429 million) acquisition of Albumedix is intended to bolster its portfolio with recombinant albumin-based solutions.

Sartorius to Acquire Albumedix for £415 Million

Catalent announced on August 9, 2022 that it has reached an agreement to acquire Metrics Contract Services, a full-service specialty contract development and manufacturing organization (CDMO), for $475 million from Mayne Pharma Group Limited.

Catalent will strengthen its capabilities in integrated oral solid formulation development, manufacturing, and packaging, as well as expand its capacity to handle highly potent compounds upon the completion of the acquisition.

The acquisition will also include Metrics’ 333,000-square-foot facility located in Greenville, NC. The facility features comprehensive capabilities to accelerate and de-risk customer programs from early development through commercial launch through a streamlines one-site solution.

“This acquisition will further expand Catalent’s ability to meet our customers’ expectations in fast-growing areas of the business and patient need. The experienced team and consistently improved, state-of-the-art facility in Greenville will provide Catalent’s customers with immediate, fit-for-scale capacity for in-demand highly potent drugs and other oral solid small-to-mid-size batch needs. This capacity is particularly important for customers with R&D pipelines featuring accelerated, orphan, and rare disease programs for oncology and other important therapeutic areas,” said Dr. Aris Gennadios, group president of Catalent’s Pharma & Consumer Health segment, in a press release.

“Over the past several years, Metrics has undergone a period of transformational change to expand its footprint and service offering, becoming a global end-to-end novel oral solid CDMO. Catalent, a global leader in advanced drug development and manufacturing, is well-positioned to continue to invest in and accelerate the growth of Metrics and we believe this transaction will be extremely positive for our Greenville team and customers,” said Scott Richards, CEO of Mayne Pharma.
Source: 

Catalent will acquire Metrics Contract Services for $475 million to expand high-potent capabilities and oral development and manufacturing capacity.

Catalent to Acquire Metrics Contract Services for $475 Million

Coherus BioSciences, a biopharmaceutical company, announced that FDA approved Cimerli (ranibizumab-eqrn) as an interchangeable biosimilar for Lucentis (ranibizumab injection) on Aug. 2, 2022. It is the first biosimilar product interchangeable with Lucentis across all five indications.

Ranibizumab-eqrn is an anti-vascular endothelial growth factor (VEGF) therapy biologic, which has been gaining traction in ophthalmology, according to a company press release. It is Coherus' second FDA approved biosimilar, following Udenyca (pegfilgrastim-cbqv), a biosimilar for Neulasta (pegfilgrastim). Coherus plans to release it in early October 2022 in both 0.3 mg and 0.5 mg dosages. Coherus also plans to release an FDA-approved Humira (adalimumab) biosimilar, Yusimry (adalimumab-aqvh), in 2023.

“[Ranibizumab-eqrn] will provide both greater treatment access and choice for patients, payors, and providers in the US retinal disease community,” said Paul Reider, chief commercial officer, Coherus BioSciences, in the press release. “Coherus is the only company in the $7 billion anti-VEGF ophthalmology market with a demonstrated track record of US commercial biosimilar success.”

“The approval of [ranibizumab-eqrn] and its upcoming launch represent a strategic inflection point for Coherus as we transition to a multi-product revenue stream,” said Denny Lanfear, CEO, Coherus BioSciences, in the press release. “[Pegfilgrastim-cbqv], our first product, established our track record of success competing in the US biosimilars market. Our upcoming launch of [ranibizumab-eqrn] and planned launch next year of our third approved product, our [adalimumab] biosimilar, [adalimumab-aqvh], will leverage this experience and knowledge.”

FDA has approved Coherus’ Cimerli (ranibizumab-eqrn) as an interchangeable biosimilar for all five indications of Lucentis.

FDA Approves Coherus’ Interchangeable Biosimilar for Lucentis

Sanofi and Innovent Biologics, a biopharmaceutical company, announced a strategic collaboration to bring oncology medicines to patients in China on Aug. 4, 2022. This agreement is designed to accelerate development and commercialization of two oncology candidates by combining them with sintilimab, a programmed cell death protein 1 immunoglobulin G4 monoclonal antibody jointly developed by Innovent and Eli Lilly and Company. According to the press release, the agreement will also see Sanofi invest €300 million (approximately $310 million USD) in Innovent.

One candidate, SAR408701 (tusamitamab ravtansine), is a potential first-in-class antibody-drug conjugate targeting carcinoembryonic antigen-related cell adhesion molecule 5, a cell-surface glycoprotein that is highly expressed in non-small cell lung cancer (NSCLC), gastric cancer, and various other cancers. Is currently in a global Phase III study for second-line NSCLC, and global Phase II studies for additional indications including first-line NSCLC, gastric cancers, and other solid tumors.

The other candidate, SAR444245 (interleukin (IL) 2), is a potential first-in-class recombinant human IL-2 variant that includes a site-directed single PEG moiety/chain that is designed to prevent it from binding to the α chain of the -2 receptor while retaining near-native affinity for the beta/gamma subunits. It is currently being investigated in global Phase II studies for the treatment of skin cancers, gastrointestinal cancer, NSCLC / mesothelioma, head and neck tumors, and lymphoma.

“This strategic collaboration with Innovent will not only accelerate the development, market access, and future commercialization of two of our key oncology medicines in selected combinations with sintilimab, but also bolster our overall presence in oncology in China,” said John Reed, global head of Research and Development, Sanofi, in the release. “We look forward to a successful partnership with Innovent, one of the most innovative companies in China, and to leveraging their development capabilities and market leadership in the country.”

“This strategic collaboration with Sanofi opens the pathway to great synergy for accelerating the pace of innovation,” said Michael Yu, chairman and CEO, Innovent, in the release. “This pioneering partnership will leverage the synergy between Sanofi and Innovent’s pipeline and R&D resources with the mutual aim to address major unmet medical needs for cancer patients.”

Sanofi and Innovent have entered into a strategic collaboration to accelerate development of oncology medicines and expand their presence in China.

Sanofi and Innovent Enter Oncology Collaboration

Jill Wechsler is Pharmaceutical Technology's Washington Editor, jillwechsler7@gmail.com.

Despite extensive opposition from biopharmaceutical manufacturers, Senate Democrats have pushed through legislation authorizing Medicare to negotiate prices on certain medicines and to limit outlays for seniors with high drug costs. The $740 billion Inflation Reduction Act (IRA) of 2022 also extends subsidies for health insurance provided under the Affordable Care Act (ACA) for an additional three years.

road package of reforms in energy and tax policy

 designed to combat global warming and to boost taxes on wealthy corporations and individuals. Republicans unanimously rejected the entire package, particularly the tax provisions and drug price controls, painting the Democrats’ plan as inflationary and fiscally irresponsible. The House is slated to vote on the bill later this week to seal this important political victory for the Biden administration. Democrats control that body by only a slim margin, setting the stage for a very tight vote in the face of stiff Republican opposition.

The prescription drug provisions in the bill will largely affect adults over age 65, as Senate rules blocked the application of certain cost controls to individuals who get health insurance through employment. The bill thus drops penalties for pharma companies that raise prices each year higher than inflation for commercial plans as well as a policy capping patients’ insulin outlays at $35 a month for consumers. Many plans already have some limits on insulin costs, but high prices on this critical drug have become a hot-button issue.

However, in a boon for health plans and consumers, the legislation delays premium increases for some 13 million individuals who currently receive discounted coverage for health insurance provided through Obamacare state and federal exchanges. Broader subsidies were authorized during the COVID-19 pandemic and are set to expire this year without the added $64 billion authorized here to continue the cost reductions in premiums for three more years.

The changes affecting Medicare drug benefits, however, are significant. The legislation would cap out-of-pocket drug costs for Medicare beneficiaries at $2000 a year beginning in 2025, a provision likely to benefit more than 1 million seniors, possibly up to 3 million as more costly therapies come to market. Pharma companies also would have to pay large “rebates” or fees to the government if they raise Medicare drug prices beyond the rate of inflation. And insulin costs would be capped at $35 a month for seniors.

Most notable is the provision authorizing Medicare price negotiations on certain costly medicines, the holy grail in health benefit reform for many Democrats for decades. Starting in 2026, this highly contentious provision will permit Medicare to negotiate prices on 10 expensive and widely used drugs near patent expiration date, expanding to 20 drugs annually by 2029. If the manufacturer rejects the Medicare price, it would pay a hefty fee to the program, a process that industry attacks as closer to price controls than to negotiations.

One thing for sure is that there will be considerable jockeying among biopharma companies over which drugs are put on the price negotiation list as the new program shakes out.

Pharmaceutical Research and Manufacturers of America 

(PhRMA) led a massive assault on the proposal, with non-stop television and radio ads predicting long-term harm to patients and the healthcare system. Similarly, the 

Biotechnology Innovation Organization (BIO)

 has kept up a steady stream of warnings that Medicare drug regulation would limit access to many important drugs and result in fewer new cures for patients. PhRMA president Steven Ubl has suggested that industry may file suit to block negotiations and will challenge new rules and other features as Medicare moves to implement the new policy.

Less visible was similar objections from the generic-drug industry to the Medicare price negotiations. The Association for Accessible Medicines (AAM) pointed out that the likely brand candidates for spending limits will be widely used, expensive medicines just as they become eligible for generic competition. However, negotiations that lower list prices will leave less room for generic makers to offer lower-priced alternatives that are profitable, and very little incentive for multiple copycats to move into the market. In addition, Medicare drug plans will have little incentive to give favorable formulary placement to only slightly less expensive generics. Biosimilar makers have raised similar issues, as negotiations to lower prices on expensive biotech therapies will make it more difficult for competing follow-ons to gain market share and become profitable.

It’s not clear, moreover, how these new policies will affect state Medicaid programs. Curbs on annual drug price increases for Medicare could raise prices for other public and private plans. New pricing policies may prompt higher launch prices for new therapies, change how formularies cover brand and generic products, and alter the design of both Medicare Part D drug plans and commercial coverage.

Another unknown is the impact of coverage and pricing policy changes on investment and innovation in the biopharma industry. Pharma and biotech manufacturers have loudly predicted that limits on prescription drug revenue from forced negotiations will curb incentives to invest in R&D, particularly in new biotech firms, reducing jobs and the discovery of many life-saving medicines. Some health analysts reject such dire outcomes, maintaining that innovation will continue as the new program spurs competition and benefits Americans more broadly.

Democrats approve curbs for Medicare plans, but not for commercial drug coverage. 

Senate Advances Drug Price Negotiations

On Aug. 4, 2022, Amgen announced a definitive agreement to acquire ChemoCentryx, a biopharmaceutical company specializing in therapeutics to treat autoimmune diseases, inflammatory disorders, and cancer, for $52 per share in cash, which represents an enterprise value of approximately $3.7 billion. Each company’s board of directors has approved the transaction, which is expected to close in the fourth quarter of 2022.

The acquisition includes Tavneos (avacopan), an orally administered selective complement component 5a receptor inhibitor. The drug was approved by FDA in October 2021 as an adjunctive treatment in combination with standard therapy for adult patients with severe active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, specifically granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the two main forms of ANCA-associated vasculitis.

ANCA-associated vasculitis is a group of multi-system autoimmune diseases with small vessel inflammation. With these diseases, inflamed vessels may rupture or become occluded, which gives rise to a broad array of clinical symptoms and signs related to a systemic inflammatory response. This may result in profound injury and dysfunction in the kidneys, lungs, and other organs.

Outside the United States, Tavneos is also approved in the European Union and Japan. Under the acquisition agreement, Vifor Fresenius Medical Care Renal Pharma will retain exclusive rights to commercialize the drug outside the US, except in Japan and Canada. In Japan, Kissei Pharmaceutical holds commercialization rights, and in Canada, Otsuka Canada Pharmaceutical holds commercialization rights.

ChemoCentryx also has three early-stage drug candidates that target chemoattractant receptors in other inflammatory diseases and an oral checkpoint inhibitor for cancer in its pipeline.

"We are excited to join in the T[avneos] launch and help many more patients with this serious and sometimes life-threatening disease for which there remains significant unmet medical need. We also look forward to welcoming the… team from ChemoCentryx that shares our passion for serving patients suffering from serious diseases," said Robert A. Bradway, chairman and CEO at Amgen, in a company press release.

"Last year, after 25 years of proud history, we at [ChemoCentryx ] delivered on our founding promise with the approval of T[avneos] for patients with [ANCA-associated vasculitis]. It is an honor to now join Amgen's great mission, and together begin a bright new era bringing landscape-shaping medicines [such as] T[avneos] to those who will benefit most," said Thomas J. Schall, president and CEO of ChemoCentryx, in the press release.

Amgen’s acquisition of Chemocentryx includes the autoimmune disease drug Tavneos (avacopan).

Amgen Will Acquire Chemocentryx in $4 Billion Deal

On Aug. 4, 2022, AstraZeneca and Merck, known as MSD outside the United States and Canada, announced that the European Commission (EC) approved Lynparza (olaparib) as monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline breast cancer gene (BRCA)1/2 mutations (gBRCAm), who have human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer. The approval is for patients previously treated with neoadjuvant or adjuvant chemotherapy.

With this approval for Lynparza in the European Union, AstraZeneca is set to receive a $75 million regulatory milestone payment from Merck.

The EC’s approval was based on results from a Phase III trial (OlympiA) and a recommendation from the Committee for Medicinal Products for Human Use. In the trial, Lynparza demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival, reducing the risk of invasive breast cancer recurrences, new cancers, or death by 42% compared to placebo. The drug also demonstrated a statistically significant and clinically meaningful improvement in overall survival, reducing the risk of death by 32% compared to placebo.

“[This] approval marks a new era of care in Europe for patients with an inherited form of breast cancer. For patients with high-risk early-stage breast cancer, including those with germline BRCA mutations, recurrence rates remain unacceptably high, with more than one in four of these patients seeing their cancer return following surgery and systemic treatment. Olaparib is the first PARP [Poly(ADP-Ribose)Polymerase] inhibitor to demonstrate improved overall survival for high-risk early-stage breast cancer patients with germline BRCA mutations, and I am hopeful it will become a new standard of care,” said Andrew Tutt, global chair of the OlympiA Phase III trial and professor of Oncology at The Institute of Cancer Research, London, and King’s College London, in a company press release.

“Today’s approval offers patients with germline BRCA-mutated HER2-negative early-stage breast cancer a new, much-needed treatment option. Lynparza as adjuvant treatment can significantly reduce the risk of disease recurrence and death, reinforcing the importance of conducting germline BRCA testing as soon as possible after diagnosis,” said Eliav Barr, senior vice-president, head of Global Clinical Development and chief medical officer, Merck Research Laboratories, in the press release.

Lynparza was approved in March 2022 in the United States for treating gBRCAm, HER2-negative high-risk early breast cancer. The drug is also approved in the US, European Union, Japan, and many other countries for treating patients with gBRCAm, HER2-negative, metastatic breast cancer previously treated with chemotherapy.

The European Commission has approved AstraZeneca and Merck’s Lynparza (olaparib) as an adjuvant treatment for BRCA-mutated HER2-negative high-risk early breast cancer.