Big Pharma bets big on AI’s US$ 148 bn potential to revolutionize healthcare industry
Artificial intelligence (AI) is changing the world and bringing efficiencies across all industries. Pharmaceuticals is one of them. AI can accelerate drug discovery, streamline clinical trials, and personalize medicine. It holds the potential to revolutionize the pharma industry.It takes anywhere between 10 to 15 years and around US$ 3 billion to take a new drug from its discovery phase to the market. AI can drastically cut both the timespan and costs and bring life-saving yet affordable treatments to the market at a faster pace. The global AI market in healthcare was estimated to be about US$ 21 billion in 2024 and is expected to grow to over US$ 148 billion by 2029, compounding at an annual growth rate of 48.1 percent.Drugmakers are eager to ride the AI wave. Players like Bayer, Merck KGaA, Moderna, BMS, Roche, Astellas, Amgen, Eli Lilly, Sanofi, Novo Nordisk and Johnson & Johnson have announced collaborations, signed deals and entered into partnerships in the AI space. Many others, such as Exscientia, Insilico, Berg, Nimbus, Recursion, and Pharos iBio, are a step ahead and are holding clinical trials on drugs developed using AI.On its part, the US Food and Drug Administration (FDA) has recognized the increased use of AI and machine learning (ML) and has reiterated its commitment to ensure the safety and efficacy of drugs “while facilitating innovations in their development.” To this end, the US agency published a paper in March that lists out its approach towards the use of AI.Novo, Lilly turn to AI for drug discovery; AI-based firms sign multiple dealsWith increased adoption of wearable devices, e-health services and other technology-driven offerings in medicine and healthcare, there is valuable data out there that drugmakers can analyze to get more accurate predictions of a drug’s effects on the human body. Such an analysis speeds up drug development and reduces side effects of therapies. Ergo, several large drugmakers have signed crucial AI deals. For example, Novo Nordisk has inked a potential US$ 2.7 billion deal with Valo Health to discover and develop novel treatments for cardio-metabolic diseases. The collaboration between the two organizations will leverage the capabilities of Valo’s Opal Computational Platform, including access to real-world patient data, AI-enabled small molecule discovery and Biowire human tissue modeling platform designed to speed up the discovery and development process.Similarly, Eli Lilly has entered into a US$ 494 million deal with Fauna Bio to use the latter’s AI platform — Convergence — for preclinical drug discovery efforts in obesity. Convergence analyzes genomic data from 452 mammal species and various tissue types to create a comprehensive dataset. By integrating human data and information from animals with natural disease resistance, the platform can identify potential drug targets.AI-based pharma firms like Isomorphic Labs and Biolojic are also landing multiple deals. Isomorphic is owned by Google’s parent Alphabet. Along with Google DeepMind, it has created a new AI model that can accurately predict 76 percent of protein interactions with small molecules. In January, Isomorphic inked deals with Novartis and Lilly for a combined value of nearly US$ 3 billion.Biolojic Design uses computational biology and AI to transform antibodies into programmable, intelligent medicines. Earlier this month, it announced a multi-target drug discovery collaboration with Merck KGaA, which includes antibody-drug conjugates. Biolojic has also inked deals with Teva and Nektar recently.Amgen harnesses generative biology for protein-based drugs; Sanofi ties up with OpenAIFinding a good protein drug candidate is like finding a needle in a haystack. Drug developers typically start by looking at proteins in nature and then go through the painstaking process of shaping them into safe and effective drugs.Generative biology is a revolutionary approach to drug discovery and development that leverages ML and AI to design novel protein therapeutics. Amgen is using generative biology to innovate new protein-based drugs that have desired structures and properties based on existing protein data inputs. In fact, the California-based multinational has said it is “integrating AI across all operational levels.” It has collaborated with PostEra to advance up to five small molecule programs.Amgen is building AI models trained to analyze one of the world’s largest human datasets on an NVIDIA full-stack data center platform, known as DGX SuperPOD, that will be installed at Amgen’s deCODE genetics’ headquarters in Reykjavik, Iceland. This system will be used to build a human diversity atlas for drug target and disease-specific biomarker discovery, providing vital diagnostics for monitoring disease progression and regression.AI can analyze individual data like genetic makeup, lifestyle and medical history to come up with personalized therapies. Amgen is working on AI-driven precision medicines, and potentially individualized therapies, at its Iceland facility.Sanofi too has signed multiple deals in recent months. In May, the French drugmaker signed a collaboration with ChatGPT maker OpenAI and Formation Bio to build AI-powered software to accelerate drug development. Sanofi is also collaborating with BioMap in a deal that could be worth up to US$ 1 billion. The deal is expected to enable superior prediction from limited data in a range of therapeutic areas, including immunology, neurology, oncology, and rare diseases.AI tools can create control arms, digital twins and slash failure rate in clinical trialsTraditional ways of drug development are fraught with challenges, and 90 percent of drug candidates in clinical trials tend to fail. Major reasons behind this are poor patient cohort selection and recruiting mechanisms, and the inability to monitor patients effectively during trials. AI tools like Trial Pathfinder study real data obtained from patients’ electronic health records and simulate clinical trials for the drug with different eligibility criteria. Trial Pathfinder also calculates trial hazard ratios, a scientific term that compares the survival rates of those given and not given the drug.AI and synthetic data can also be used to create control arms in clinical trials, which can help speed up the process, reduce costs, and improve the quality of data. For example, FDA has supported the use of a Medidata Synthetic Control Arm in a phase 3 trial of Medicenna’s MDNA55 in recurrent glioblastoma.In addition to observing real-time patient data, researchers can also create digital twins, virtual replicas of cells, organs, or people, which they can use to simulate and predict various clinical outcomes during a trial.Our viewThe pharmaceutical industry is on the cusp of a revolution. In the coming years, we hope to see some tangible results of the efforts being put in by drugmakers, AI developers and regulatory agencies. The CPhI Annual Report 2023 has predicted that in 2030, over half of FDA-approved drugs will involve AI in their development and/or manufacturing. The winner, in our view, will be the end-user who will have cheaper, safer and more effective treatments, delivered at a faster pace.

Impressions: 652

13 Jun 2024
DMF submissions from China jump 42% as India continues to top list in Q1 2024
Generic drugs play a crucial role in providing access to life-saving drugs at affordable prices. To that end, drugmakers submit Drug Master Files (DMFs) or their ‘recipes for making generics’ to the US Food and Drug Administration (FDA) for review. Of these, Type II DMFs involve active pharmaceutical ingredients (APIs) for both branded and generic drugs.PharmaCompass has been reviewing Type II submissions for several years now. We have noticed that these filings have been increasing in recent years. There has been a 33.5 percent increase in Type II DMF submissions since Q1 2018 (when 176 Type II DMFs had been submitted). However, at 235, the first quarter (Q1) of 2024 saw only a 1.3 percent increase in DMF submissions over Q1 2023. In Q1 2023, DMF submissions had increased by 21.5 percent (over Q1 2022).Of the 235 Type II submissions received by the FDA in Q1 of this year, only 35 (or around 15 percent) had their review completed under the Generic Drug User Fee Act (GDUFA). The total number of reviews completed by the US federal agency so far this year is 129.In all, FDA received 353 Type II, III, IV, and V DMF submissions, compared to 291 in Q1 2023, an increase of 21.3 percent.View FDA DMF Filings in Q1 2024 (Power BI Dashboard, Free Excel Available)DMF submissions from India dip 1.8%; China witnesses 42% rise in filings As has been the trend, India (dubbed as the pharmacy of the world) and China filed the maximum DMF submissions, with 107 and 101 submissions respectively. However, DMFs filed by Indian companies saw a marginal dip of 1.8 percent in Q1 2024 — in Q1 2023, Indian companies had filed 109 Type II DMFs. Meanwhile, DMF filings by Chinese drugmakers increased 42.2 percent in Q1 2024, up from 71 in Q1 2023.India’s MSN Laboratories was the clear leader with 15 DMF submissions to the FDA, while China’s Sichuan Elixir Pharmaceutical came a distant second with nine submissions. Indian drugmakers Aurobindo Pharma and Global Calcium (with seven submissions each) were tied at third position. There were two players at the fifth spot — India’s Dr. Reddy’s Laboratories and China’s Zhejiang Jingsheng Pharmaceutical — as both these drugmakers registered six submissions each.View FDA DMF Filings in Q1 2024 (Power BI Dashboard, Free Excel Available) Diabetes, cancer drugs emerge as hot molecules in Q1 2024Approved in June 2020, triheptanoin is the first and only FDA-approved treatment for children and adults with long-chain fatty acid oxidation disorders (LC-FAOD). At five, triheptanoin saw the maximum DMF filings. Four of those applications have already been positively reviewed.Anti-diabetic drug sitagliptin phosphate monohydrate saw four DMF filings. Empagliflozin, the API found in Boehringer Ingelheim and Eli Lilly’s diabetes drug Jardiance, drew three DMF filings in Q1 2024.In the US, Jazz Pharmaceuticals’ Zepzelca (lurbinectedin) is indicated for the treatment of adult patients with metastatic small cell lung cancer (SCLC). Three DMF applications were submitted for lurbinectedin. Similarly, ruxolitinib phosphate, used for the treatment of patients with intermediate or high-risk myelofibrosis, also received three DMF applications.Semaglutide — the glucagon-like peptide-1 receptor agonist that catapulted Novo Nordisk to the position of the most valuable public company in Europe — received three DMF filings. Semaglutide’s arch rival, tirzepatide, also drew three DMF filings.AstraZeneca’s Brilinta (ticagrelor) plus aspirin is currently approved in over 115 countries for the prevention of stroke, heart attack, and other events in adults with acute coronary syndrome (ACS). Ticagrelor received three DMF submissions. Vonoprazan fumarate, a first-in-class potassium-competitive acid blocker to treat acid-related diseases, also received three DMF submissions.View FDA DMF Filings in Q1 2024 (Power BI Dashboard, Free Excel Available) Eighteen DMFs filed for first time in Q1 2024 During the first quarter of this year, 14 drugs saw first time filing of DMFs. Together, these 14 drugs attracted 18 DMF filings with tirzepatide topping the list with three submissions from Chinese companies.The 14 drugs that saw first time filing were clascoterone, capmatinib hydrochloride, niraparib tosylate monohydrate, vibegron, cabozantinib sulfate, ruxolitinib hemifumarate, ripretinib, ruxolitinib, ruxolitinib mesylate, tucatinib hemiethanolate, tecovirimat, tirzepatide, tolvaptan povidone, and azilsartan.View FDA DMF Filings in Q1 2024 (Power BI Dashboard, Free Excel Available) Our viewUntil 2020, DMF submissions by Indian companies used to be double those of Chinese and American firms put together. In 2022, DMF filings from India began to dip, while submissions by Chinese companies began to rise. In the first half of 2023, there was a 46.5 percent rise in DMF submissions from China. The gap between DMF filings by India and China has narrowed down considerably this year. The reasons behind this phenomenon may be multiple. But it definitely implies that America will find it increasingly difficult to reduce its reliance on China.

Impressions: 1652

23 May 2024
Top Pharma Companies & Drugs in 2023: Merck’s Keytruda emerges as top-selling drug; Novo, Lilly sales skyrocket
The pharma industry clearly recalibrated itself in 2023, turning its focus away from Covid and onto two of the biggest threats to human health – obesity and cancer. The top lines of the major pharma companies reflect this shift in focus.We always knew that Pfizer’s record US$ 100 billion revenue for 2022 wasn’t sustainable. Even though Pfizer’s 2023 sales were lower by nearly 42 percent against its 2022 sales, the New York-headquartered drugmaker managed to retain its pole position. The two main reasons behind its ‘top of the charts’ sales of US$ 58.5 billion were Pfizer’s record nine new molecular entity approvals by the US Food and Drug Administration (FDA) and the launch of its vaccine for respiratory syncytial virus (RSV).Johnson & Johnson came second with sales of US$ 54.8 billion (excluding its consumer business and MedTech units). AbbVie took bronze despite Humira being subject to biosimilar competition and Merck maintained its fourth position. Roche nabbed the fifth position from Novartis (which stood sixth). Bristol Myers Squibb maintained its position at seven, as did AstraZeneca (eighth) and Sanofi (ninth). And Eli Lilly bumped into the tenth spot, knocking out GSK.View Our Interactive Dashboard on Top Drugs in 2023 by Sales (Free Excel Available)Keytruda, Eliquis, Humira top charts; Novo’s Ozempic debuts top 10 list at number fourMerck’s Keytruda became the number one selling drug in the world, a position that was held by AbbVie’s Humira for long, and Pfizer’s Comirnaty in the Covid years. This oncology drug raked in a whopping US$ 25 billion, with sales increasing 19 percent last year. In fact, Keytruda accounted for 46.7 percent of Merck’s pharmaceutical sales, which grew 3 percent in 2023 to US$ 53.6 billion.At number two was Pfizer and BMS’ anticoagulant Eliquis — it posted global sales of US$ 18.95 billion (marking a growth of 4 percent on 2022 sales). With competition from generics, Humira’s sales fell by 32 percent to US$ 14.5 billion. As a result, this blockbuster anti-rheumatic drug fell to the third rank.The fourth spot was taken up by Novo Nordisk’s Ozempic, the wonder drug that treats type 2 diabetes. Gilead’s Biktarvy, a med that treats HIV-1, saw sales jump 14 percent — from US$ 10.39 billion posted in 2022 to US$ 11.85 billion last year. This way, Biktarvy emerged as the fifth largest selling drug of 2023.At number six was Sanofi and Regeneron’s Dupixent. This allergic diseases med posted 11-figure sales in 2023, netting € 10.72 billion (US$ 11.59 billion) globally, a growth of 34 percent over 2022 numbers.At number seven was J&J’s biggest blockbuster immunology drug Stelara that raked in US$ 11.3 billion in 2023. Coming a close eighth was Pfizer-BioNTech’s Covid-19 vaccine Comirnaty — its sales fell by over 70 percent to US$ 11.22 billion in 2023. At the ninth spot was Lilly and Boehringer’s diabetes drug Jardiance that saw a 27.7 percent increase in total global sales at US$ 10.6 billion. And rounding off the list at number 10 is BMS’s Opdivo, a Keytruda rival. Opdivo hauled in US$ 10 billion in total global sales in 2023, a year-on-year increase of 8 percent.View Our Interactive Dashboard on Top Drugs in 2023 by Sales (Free Excel Available)Driven by diabetes, obesity care meds, Novo, Lilly post double-digit sales growthDemand for diabetes and new weight-loss drugs catapulted Novo Nordisk to emerge as the most valuable public company in Europe. Its net sales zoomed 31 percent to DKK 232.3 billion (US$ 33.75 billion) compared to DKK 177 billion (US$ 25.8 billion) in 2022. Net profit jumped 51 percent to DKK 83.68 billion (US$ 12.51 billion) in 2023 from DKK 55.5 billion (US$ 8.32 billion) in 2022 — the highest annual profit for the Danish drugmaker in over three decades.The growth was driven by Ozempic, whose sales spiked 60 percent in 2023 to DKK 95.7 billion (US$ 13.91 billion), from DKK 59.8 billion (US$ 8.71 billion) the year before.Rival Eli Lilly’s revenue grew 20 percent in 2023 to US$ 34.1 billion from US$ 28.5 billion in 2022. Mounjaro turned out to be a star for the Indianapolis drugmaker with its sales rocketing 970 percent in 2023 to US$ 5.16 billion. FDA also approved it to treat obesity under the brand name Zepbound in November, which brought in additional revenues of US$ 176 million.View Our Interactive Dashboard on Top Drugs in 2023 by Sales (Free Excel Available) GSK’s RSV jab makes strong debut; AbbVie’s immunology drugs post steep growthGSK’s Arexvy was the first RSV vaccine approved by the FDA. It made a strong debut — Arexvy contributed £ 1.2 billion (US$ 1.5 billion) to GSK’s sales in just four months.AbbVie posted another solid financial year. Though the drop in Humira revenue was offset by two newer immunology blockbuster drugs, Skyrizi and Rinvoq, the Illinois-headquartered drugmaker did posted a marginal decrease in revenue of 6.4 percent to US$ 54.3 billion. However, revenue from Skyrizi soared 50 percent to US$ 7.8 billion, while Rinvoq’s sales increased 57 percent to US$ 4 billion. AbbVie expects a combined US$ 16 billion from Skyrizi (US$ 10.5 billion) and Rinvoq (US$ 5.5 billion) sales in 2024. BMS attributed its 2 percent decrease in revenue (of US$ 45 billion) to lower sales of Revlimid in the US due to competition from generics. Sales of the multiple myeloma treatment dropped 39 percent to US$ 6.1 billion. Ophthalmology drug Eylea saw a drop in sales  of 4 percent, at US$ 9.21 billion (from US$ 9.65 billion), as competition from Roche’s Vabysmo triggered a price cut by Regeneron. Vabysmo saw sales balloon 324 percent from CHF 591 million (US$ 685.56 million) to CHF 2.4 billion (US$ 2.78 billion) in 2023.View Our Interactive Dashboard on Top Drugs in 2023 by Sales (Free Excel Available) Our viewAccording to data analytics company GlobalData, GLP-1 agonist drugs (such as Ozempic and Mounjaro that treat type 2 diabetes) are slated to overtake PD-1 antagonists (such as oncology drugs Keytruda and Opdivo) as the top-selling drugs on the market in 2024. It estimates a robust compounded annual growth rate (CAGR) of 19.2 percent from 2023 to 2029 for GLP-1 drugs that seem to have more benefits besides bringing down blood sugar levels (such as weight management, benefits to the heart etc).The market size for GLP-1 is likely to increase to US$ 105 billion by 2029. In contrast, the data firm projects a CAGR of 4.7 percent in the PD-1 antagonist market, with its market size projected to be around US$ 51 billion in 2029. Given these projections, we are likely to see more movers and shakers in our top 10 drug list this year.

Impressions: 2652

25 Apr 2024
FDA approves four oligonucleotide therapies in 2023; Novartis, GSK, Novo bet big
In the intricate world of molecular biology, oligonucleotides stand out as versatile, powerful molecules. Oligonucleotides are essentially short, single strands of DNA or RNA that modulate gene expression. There are various oligonucleotide therapy (ONT) agents (such as antisense, deoxyribozymes, siRNA and CRISPR/Cas) that offer promising therapeutic tools.A variation of gene therapy, oligonucleotide gene therapies (OGTs) are manufactured using synthetic oligonucleotides. These therapies are designed to enter cells. ONTs act like tools that can fine-tune the behavior of certain genetic instructions, and are therefore often designed to treat rare and genetic diseases and cancers. Sometimes, they may be delivered into cells through lipid nanoparticles or adeno-associated viruses (AAV), halting the translation of a specific protein. Oligonucleotides have also revolutionized vaccine development through the creation of nucleic acid vaccines, such as mRNA vaccines.The first oligonucleotide drug, known as fomivirsen, was approved by the US Food and Drug Administration (FDA) back in 1998. It was developed by Ionis Pharmaceuticals (then known as Isis Pharmaceuticals), and was approved to treat a rare eye disease. However, ONT approvals have picked up since 2016. Currently, there are 20 oligonucleotide drugs approved by the FDA and the European Medicines Agency (EMA) and a majority of them treat orphan and rare diseases.In 2023, FDA approved four ONTs — AstraZeneca-Ionis’ Wainua (eplontersen), Novo Nordisk owned Dicerna Pharmaceuticals’ Rivfloza (nedosiran), Biogen-Ionis’ Qalsody (tofersen) and Iveric Bio’s Izervay (avacincaptad pegol).In 2021, the global ONT market size was estimated to be US$ 18.2 billion. It is expected to increase to US$ 51.4 billion by 2029, growing at a compounded annual rate (CAGR) of 13.85 percent. Similarly, the market for oligonucleotides synthesis (or the process of producing oligonucleotides) was estimated at US$ 7.7 billion globally in 2022 and is expected to grow 11.8 percent CAGR to reach US$ 16.4 billion by 2030. Some of the bigger players in oligonucleotides synthesis are Danaher Corporation, Thermo Fisher Scientific, Merck KGaA, Eurofins, Agilent, Bio-Synthesis, EUROAPI, Eurogentec, STA Pharma, and Bachem.View Our Interactive Dashboard on Oligonucleotide Therapies (Free Excel Available)ONTs address neuro disorders; four ONTs bring in US$ 1.24 bn for AlnylamONTs are widely applied to treat neurodegenerative diseases, such as Duchenne muscular dystrophy (DMD). Multiple ONTs have been approved in Europe and the US for DMD, such as Exondys 51 (eteplirsen), Vyondys 53 (golodirsen), and Amondys 45 (casimersen) from Sarepta and NS Pharma’s Viltepso (viltolarsen). Last year, Ionis bagged two approvals in the space. FDA approved its Biogen-partnered therapy Qalsody (tofersen) to treat patients with amyotrophic lateral sclerosis (ALS). The agency also approved AstraZeneca and Ionis’ drug Wainua (eplontersen), rendering it as the first self-administered treatment for a rare nerve damage disease, known as hereditary transthyretin amyloidosis (ATTR-PN). Analysts estimate global peak sales for Wainua to come in at US$ 750 million for ATTR-PN alone. The drug is also being tested for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), a rare heart muscle disorder.Alnylam Pharmaceuticals has also successfully brought four ONTs to market in recent years — Onpattro (patisiran) and Amvuttra (vutrisiran) for rare nerve diseases, and Givlaari (givosiran) and Oxlumo (lumasiran). Givlaari has been approved to treat acute hepatic porphyria (a liver enzyme deficiency) while Oxlumo treats primary hyperoxaluria (a disorder characterized by increased urinary oxalate excretion). The four ONTs brought in US$ 1.24 billion for Alnylam in 2023.View Our Interactive Dashboard on Oligonucleotide Therapies (Free Excel Available) Novartis buys rights to siRNA therapy, GSK bets big on ONT pipeline through dealsAfter Alnylam discovered inclisiran (Leqvio), Novartis acquired global rights to the therapy in a US$ 9.7 billion deal. Leqvio was the first FDA-approved small interfering RNA (siRNA) therapy for LDL-C (bad cholesterol) reduction. It brought in US$ 355 million for Novartis in 2023.GSK has increasingly been investing in its ONT pipeline. The British pharma has promised over US$ 5 billion in upfront and milestone payments in multiple deals. In February, GSK exercised its option to license Elsie Biotechnologies’ discovery platform to find and develop novel ONTs. GSK has also entered a discovery collaboration with Wave Life Sciences.Last July, Japanese drugmaker Astellas Pharma completed its approximately US$ 5.9 billion buyout of New Jersey-headquartered Iveric Bio. Iveric focuses on retinal diseases and the deal gives Astellas drug candidates to treat about 160 million people with eye ailments. Subsequently, in August, Iveric’s Izervay (avacincaptad pegol) was approved by the FDA as a new treatment for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).After Novo Nordisk acquired RNAi technology company Dicerna Pharmaceuticals for US$ 3.3 billion in 2021, the latter’s once-monthly RNAi therapy Rivfloza (nedosiran) saw FDA approval last October. Rivfloza was okayed for children nine years and older to treat a rare genetic condition that affects the kidneys, known as primary hyperoxaluria type 1 (PH1).View Our Interactive Dashboard on Oligonucleotide Therapies (Free Excel Available) Ionis tees up NDAs for rare disease treatments after two late-stage trial winsThe industry is looking for cures to a wide spectrum of diseases like cancer (such as melanoma, pancreatic, liver, glioblastoma, breast and ovarian cancer), cystic fibrosis, Alzheimer’s disease, Parkinson’s disease, hepatitis B, asthma, Rett syndrome, non-alcoholic steatohepatitis, and IgA nephropathy through its research on ONTs.In January, Ionis announced late-stage results wherein its RNA-targeted hereditary angioedema (HAE) candidate, donidalorsen, significantly reduced the rate of HAE attacks in patients treated every four weeks and patients treated every eight weeks. The California-based biotech is readying a new drug application (NDA) to submit to the FDA. HAE is a rare and life-threatening genetic disease that causes unpredictable and frequent severe swelling of the skin, gastrointestinal (GI) tract, upper respiratory system, face and throat. This year, Ionis’ olezarsen was granted fast track designation by the FDA for the rare genetic disease familial chylomicronemia syndrome (FCS). Last September, olezarsen had met its primary endpoint of reducing abnormally high levels of triglycerides in a late-stage trial in patients with the metabolic disorder. Currently, there are no FDA-approved treatments for this condition. If okayed, olezarsen is likely to bring in US $849 million in sales for Ionis by 2032.In March, FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 12 to two in favor of the clinical benefit/risk profile of imetelstat for the treatment of transfusion-dependent (TD) anemia in certain adult patients with myelodysplastic syndromes. The agency assigned a Prescription Drug User Fee Act (PDUFA) target action date of June 16, 2024, for Geron’s NDA for imetelstat. It is among the most anticipated drug launches this year.View Our Interactive Dashboard on Oligonucleotide Therapies (Free Excel Available) Our viewDeveloping ONTs is a field fraught with challenges, such as toxicity and drug delivery. There are safety concerns as well as concerns around delivering the therapy. However, technological breakthroughs and collaborations between pharma firms and contract research organizations that focus on drug delivery are continuously working towards addressing these challenges. All in all, we foresee exciting times ahead for ONTs.  

Impressions: 2548

21 Mar 2024
FDA steps in to address challenges faced by cell and gene therapies
The year 2023 was a rather tough one for cell and gene therapy (CGT) companies. There was news about smaller CGT players finding it difficult to get finance, with many drastically downsizing their operations by laying off hundreds of employees. Many others had to shut shop, making us wonder if innovation in the biopharma industry is in for a setback.The new year began on a sour note, with the FDA shooting off letters to six manufacturers of cancer therapies that use CAR-T technology to add a boxed warning on their label after the agency found a serious risk of developing secondary cancer. These therapies include Bristol-Myers Squibb’s Abecma and Breyanzi, Janssen Biotech’s Carvykti, Gilead’s Yescarta, Novartis’ Kymriah and Kite Pharma’s Tecartus. “Boxed warnings” or “black box warnings” are the highest safety warnings. A week later, FDA stepped in and finalized guidance for companies and academic researchers working on CAR-T cell therapies.In this article, PharmaCompass looks at some of the challenges being faced by CGT firms, and the growth prospects of this sunrise sector.A field with complex manufacturing, high costs of developmentThere are several ways in which CGTs can target a disease, giving rise to various kinds of such therapies. These include gene addition, gene silencing, gene editing, DNA therapy (such as DNA plasmids and viral vectors), RNA therapy (ribosomal RNA, messenger RNA, microRNA, small interfering RNA and transfer RNA), antisense oligonucleotides and gene-modified cell therapy (such as CAR T-cell therapies and Treg cell therapies). CGTs are being deployed to treat several kinds of diseases, such as various types of cancers, including brain tumors, breast and colon cancers, as well as leukemia. Other major therapeutic areas CGTs are making an impact on are genetic and rare diseases like sickle cell disease (SCD), β-thalassemia, hemophilias, and paraplegia. CGTs are also being explored for treating Duchenne muscular dystrophy, Alzheimer's disease, Parkinson’s disease, multiple sclerosis, type 1 diabetes and macular edema.Going by FDA’s Purple Book, there are 35 CGT products approved in the US. With three FDA approvals, bluebird bio tops the list (with Lyfgenia, Zynteglo, and Skysona), followed by Bristol Myers Squibb (with Abecma and Breyanzi), Kite Pharma (with Tecartus and Yescarta), and Novartis (with Zolgensma and Kymriah). Recently, FDA approved Vertex Pharma-CRISPR Therapeutics’ Casgevy, the first gene-editing therapy that uses the Nobel-prize-winning CRISPR technology.Though CGTs are personalized therapies, they come with potential risks, such as developing certain kinds of cancers, genotoxicity, allergic reactions, damage to the organs etc.Another challenge faced by CGTs is costs. Apart from the high R&D costs, these biotechs face other challenges such as high costs of reagents like clinical-grade lentiviral vectors or gene editing reagents, as well as cell processing materials, GMP facilities and personnel costs.Little wonder then that the selling price of some of the CGTs run into millions of dollars. CSL Behring and uniQure’s Hemgenix, a first-of-its-kind drug for hemophilia B, is the most expensive drug in the world. It costs a whopping US$ 3.5 million. Similarly, bluebird bio’s Lyfgenia, a therapy that has the potential to resolve vaso-occlusive events and is custom-designed to treat the underlying cause of SCD, costs US$ 3.1 million.Smaller CGT firms get strapped for funds, fail to land Big Pharma dealsTypically, innovation for CGTs happens at small biotechs or universities. Many of the small firms get acquired by bigger drugmakers or tie up with larger pharma companies so that volumes can be scaled up once the therapy is approved.Last year, scores of biotechs announced bankruptcies. Many smaller biotechs failed to land Big Pharma deals. They had to contend with narrower funding options, forcing several startups in the sector to shut shop. For example, Intergalactic Therapeutics shut down last year, after being around for less than two years. The company said: “The current environment has led to challenging times for companies to raise capital,” even though Intergalactic’s programs have “shown promise”. Other CGT firms that shut shop last year were Locanabio, Vedere Bio II and CODA Biotherapeutics.Companies that laid off employees to cut costs are base editing biotech Beam Therapeutics, Editas Medicine, Sangamo Therapeutics, Graphite Bio, UniQure, Generation Bio, Candel Therapeutics, Lyell Immunopharma, BrainStorm Cell Therapeutics and Nkarta. CRISPR Therapeutics, ElevateBio and Atsena also reportedly laid off employees. FDA lines up initiatives, to make 2024 ‘breakout’ year for gene therapiesThe “personalized nature” of CGTs makes them highly effective. But this trait also gives rise to multiple challenges. Acknowledging this, in January, FDA announced a pilot program called Collaboration on Gene Therapies Global Pilot (CoGenT Global) to streamline regulations pertaining to this sector. The agency has also addressed challenges such as the high cost of manufacturing, clinical development timelines, macroeconomic conditions (such as high interest rates), and operational issues being faced by CGTs. FDA is promising to make 2024 a “breakout” year for gene therapies, with a number of initiatives to promote clinical development, approvals and uptake. FDA’s Center for Biologics Evaluation and Research (CBER) is sponsoring research and encouraging collaboration with the National Institutes of Health’s Bespoke Gene Therapy Consortium. The agency has made gene editing therapies eligible for accelerated approval and detailed the information that should be provided in an investigational new drug (IND) application. It has also launched a pilot program Support for clinical Trials Advancing Rare disease Therapeutics (START), with the intention of speeding up development.Our viewIn 2022, Precedence Research estimated the CGT market at US$ 15.46 billion, expecting it to increase fivefold by 2032 to touch US$ 82.24 billion, with therapeutic areas such as oncology (US$ 10.4 billion) and genetic disorders (US$ 8.57 billion) expected to draw most revenues.FDA approved seven CGTs in 2023, including Casgevy. But this year, FDA and European regulators may approve as many as 17 gene therapies. A McKinsey report says in 2024 alone, “up to 21 cell therapy launches and as many as 31 gene therapy launches—including more than 29 adeno-associated virus (AAV) therapies—are expected.” Given these estimates, we have little doubt that 2024 will be a “breakout year” for CGTs.  

Impressions: 2132

22 Feb 2024
FDA approvals rise 49% in 2023; CRISPR’s gene editing therapy sees light of day
In 2022, when the US Food and Drug Administration (FDA) was reeling under the impact of the pandemic, new drug approvals by the agency dropped by 26 percent. But last year, FDA’s new drug approvals rebounded by an impressive 49 percent, with the Center for Drug Evaluation and Research (CDER) approving 55 new drugs in 2023. Of them, 36 percent were considered first-in-class, while small molecules made up for 62 percent of the total drugs approved (i.e. 34). FDA’s Center for Biologics Evaluation and Research (CBER) okayed 19 biologics in 2023 compared to eight in the previous year.The first half of 2023 saw the debut of vaccines for the all-too-common respiratory syncytial virus (RSV). Among the other notable approvals in H1 was Biogen and Eisai’s Alzheimer’s drug Leqembi (lecanemab). Out of the total 55 drug approvals, 29 came in H2 2023. This includes Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy that relies on the Nobel Prize-winning CRISPR gene-editing technology. Casgevy has been approved as a treatment for sickle-cell disease (SCD) and β-thalassemia.While FDA witnessed a sharp rise in approvals in 2023, many other drug regulators didn’t. The European Medicines Agency (EMA) granted marketing authorization to 32 novel drugs in 2023, a fall from 33 in 2022. Similarly, Health Canada’s approvals in 2023 decreased to 38, compared to 45 in the previous year.As usual, oncology topped the list of drug approvals by therapeutic area, at 39 (as opposed to 35 in 2022). Rare diseases was the second most popular therapeutic area for drug approvals. With drugmakers clearly paying heed to the unmet needs of patients suffering from rare diseases, this therapeutic area sprinted from a 9 percent share and the fourth position among new approvals in 2022 to an impressive 34 percent share in 2023. A quarter of the new drug approvals were in infectious diseases, followed by immunology (19 percent) and neurology (7 percent).View New Drug Approvals in 2023 with Estimated Sales (Free Excel Available) Casgevy, postpartum depression drug Zurzuvae emerge as potential blockbustersGene therapy Casgevy, postpartum depression (PPD) med Zurzuvae, blood cancer med Elrexfio and ulcerative colitis drug Velsipity were some of the prominent approvals of 2023.Britain’s Medicines and Healthcare products Regulatory Agency was the first to okay Casgevy in November as a cure for SCD and β-thalassemia. Soon, the FDA approved it for SCD. In January this year, the American agency also approved it for transfusion-dependent β-thalassemia (TDT). Analysts estimate Casgevy to generate US$ 2.6 billion in peak sales, says Nature. Biogen and Sage’s PPD therapy Zurzuvae became the first and only FDA-approved pill for the condition that can be life-threatening for both the mother and the child. Global sales of Zurzuvae are forecast to hit US$ 1.28 billion by 2028.In August, Pfizer’s Elrexfio (elranatamab) became the first “off-the-shelf” (ready-to-use) therapy in the US for multiple myeloma. The drug provides an option for patients with hard to treat or relapsed blood cancer and is estimated to bring in US$ 861 million in peak sales by 2028, says Nature.Pfizer also bagged another significant approval in October — its drug Velsipity (etrasimod) was greenlit by the FDA to treat adults with ulcerative colitis, an inflammatory bowel disease. Peak revenue for Velsipity is expected to come in at US$ 825 million, as per Evaluate.View New Drug Approvals in 2023 with Estimated Sales (Free Excel Available) Astra’s Truqap, GSK’s Ojjaara among top cancer therapies given FDA nod in H2In November, FDA approved AstraZeneca’s Truqap (capivasertib) in combination with the Anglo-Swedish drugmaker’s Faslodex (fulvestrant) for treating adult patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations. Evaluate Pharma forecasts peak Truqap sales to come in at about US$ 690 million.In September, FDA approved GSK’s Ojjaara (momelotinib) as the first and only treatment for myelofibrosis with anemia. Nearly all myelofibrosis patients are estimated to develop anemia over the course of the disease. Ojjaara is taken orally once a day.Other notable oncology treatments okayed by FDA in H2 2023 include Daiichi’s Vanflyta (quizartinib) in July to treat an aggressive blood cancer known as acute myeloid leukemia (AML). In August, FDA approved Janssen’s bispecific antibody Talvey (talquetamab-tgvs) for difficult-to-treat blood cancer. The agency approved two cancer therapies in November — BMS’ Augtyro (repotrectinib) for ROS1-positive non-small cell lung cancer (NSCLC) and Takeda’s targeted oral therapy Fruzaqla (fruquintinib) for adult patients with metastatic colorectal cancer (mCRC).View New Drug Approvals in 2023 with Estimated Sales (Free Excel Available) Rare disease drugs Santhera-Catalyst’s Agamree, Novo’s Rivfloza bag approval in H2In October, FDA approved Santhera Pharmaceuticals and Catalyst Pharma’s Agamree (vamorolone), an oral suspension treatment for Duchenne muscular dystrophy (DMD) in patients two years of age and older. This makes it the first drug fully approved in both the US and Europe for the muscle degeneration disorder. Agamree acts in a manner similar to other steroids, which are the standard of care for the inherited rare disease. However, it causes fewer side effects.FDA also okayed Novo Nordisk’s once-a-month injection Rivfloza (nedosiran) in October to treat a rare genetic condition — primary hyperoxaluria type 1 (PH1) — that causes recurring kidney stones.In November, the agency approved Takeda’s Adzynma (ADAMTS13, recombinant-krhn) as the first treatment for both adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP), a rare genetic blood disorder. Other noteworthy FDA approvals in H2 2023 for rare blood diseases include Novartis’ Fabhalta and bluebird bio's Lyfgenia. Fabhalta is the first oral monotherapy for the treatment of adults with paroxysmal nocturnal hemoglobinuria, a rare disease that causes symptoms such as hemolytic anemia, hemoglobinuria (excretion of hemoglobin in the urine), fatigue, shortness of breath etc. Lyfgenia is the first cell-based gene therapy for the treatment of SCD in patients 12 years and older. Similarly, another rare disease drug — Regeneron’s Veopoz —  bagged FDA approval in August last. Veopoz treats CHAPLE disease, an ultra-rare disease in which patients have severe gastrointestinal problems.View New Drug Approvals in 2023 with Estimated Sales (Free Excel Available) Our viewAfter a lull in 2022, new drug approvals have finally gathered momentum. The good news is that this year, several pathbreaking drugs are coming up for approval, such as Madrigal Pharmaceuticals’ resmetirom (the first treatment for NASH with liver fibrosis), Merck’s sotatercept (a treatment for pulmonary arterial hypertension), Lilly’s donanemab for Alzheimer’s disease and Karuna Therapeutics’ drug to treat schizophrenia. Let’s hope 2024 turns out to be an even bigger year for new drug approvals.

Impressions: 2648

01 Feb 2024
Pfizer’s buyout of Seagen, drugmakers suing US govt, obesity drugs make it to top 10 Phispers of 2023
Every week, PharmaCompass compiles important developments in the world of pharmaceuticals and brings a compilation to you in the form of Phispers. Of the hundreds of stories we carried in 2023, here are the top 10 stories, including some trends and updates.I. Pfizer buys Seagen for US$ 43 billion to bolster its oncology portfolioIn March, Pfizer said it is acquiring cancer treatment specialist Seagen for US$ 43 billion. Seagen is a pioneer in antibody-drug conjugates (ADCs), or drugs that work like “guided missiles” to destroy cancer cells while sparing healthy cells. Another important deal in the field of ADCs took place in December when AbbVie picked up ImmunoGen for US$ 10.1 billion, giving it access to Elahere (mirvetuximab soravtansine-gynx), an ADC approved for platinum-resistant ovarian cancer. Elahere is expected to achieve blockbuster status by 2030. II. Merck, BMS, trade bodies, sue US government over IRA negotiationsIn June, Merck filed a lawsuit against the US government seeking to block Medicare from negotiating lower prescription drug prices under the Inflation Reduction Act (IRA). Days later, the US Chamber of Commerce, one of the most influential trade groups in the US, filed a separate lawsuit, arguing that the negotiations violated drugmakers’ constitutional rights and granted excessive control over prices to the government. They were joined by Bristol Myers Squibb (BMS) and lobby group PhRMA. Drugmakers and the Biden administration appeared to be at each other’s throats. In December, the White House identified 48 drugs whose prices spiked faster than inflation in Q4. These drugs may be subject to rebates starting January 2024. Biden Administration also announced it is setting a new “march-in” policy that allows the government to seize medicine patents held by drugmakers for therapies whose development was taxpayer-funded, if it believes they are not “reasonably available and affordable.”III. US, UK approve Lilly’s Mounjaro for weight management; to be sold as ZepboundIn November, drug regulators in the US and the United Kingdom approved Eli Lilly's Mounjaro (tirzepatide) for weight management, to be sold under the brand name Zepbound. The drug will pose strong competition to Novo Nordisk’s Wegovy in a market that's expected to reach US$ 100 billion by the end of the decade.IV. Novo, Lilly plan capacity expansions for weight loss drugsBoth Novo Nordisk and Eli Lilly announced expanding their manufacturing capacities in order to capitalize on the burgeoning market for weight loss drugs. Novo is investing over DKK 42 billion (US$ 6 billion) in Kalundborg (Denmark), US$ 2.3 billion to expand its site in Chartres (France) and over € 2 billion (US$ 2.18 billion) in Dublin (Ireland) to boost production of its blockbuster diabetes and weight-loss drugs, including Ozempic and Wegovy (both semaglutide). Similarly, Eli Lilly had announced a US$ 2.5 billion manufacturing facility in Germany in November to address the demand for its new obesity and diabetes therapies.V. FDA finds violations at Global Pharma’s eye drops plant in India; issues Form 483In April, FDA found several violations in manufacturing processes and sterilization methods used by India-based Global Pharma for its EzriCare Artificial Tears Eye Drop, which has been linked to 68 cases of eye infection in the US, including eight cases of vision loss and three deaths.VI. ‘Intas India staff tore documents, threw acid to destroy evidence’, notes FDAIn January, FDA issued a Form 483 with 11 observations to Intas Pharma’s drug manufacturing facility in Ahmedabad (Gujarat, India). A team of three FDA drug regulators conducted an inspection of the manufacturing facility from November 22 to December 2, 2022. The 36-page report issued by the FDA has alleged that employees at the facility had destroyed documents related to manufacturing practices by tearing them into pieces and disposing them inside the quality control lab and scrap areas. Acid was used to destroy evidence, notes FDA.VII. GSK overtakes Pfizer in bagging first FDA approval for RSV vaccineIn May, FDA approved GSK’s respiratory syncytial virus (RSV) vaccine for people aged 60 and above. Arexvy is the first RSV vaccine to be approved in the US for the common condition that can be fatal for the elderly. Later that month, Pfizer’s RSV vaccine Abrysvo also got approved. In July, Sanofi-AstraZeneca’s RSV antibody therapy, Beyfortus (nirsevimab-alip), received approval from the FDA. It is a long-acting treatment that can be given once per season. The approval is specifically developed for newborns and infants.VIII. UK authorizes gene therapy Casgevy for blood disorders, US follows suit In November, Britain’s Medicines and Healthcare products Regulatory Agency was first off the block in authorizing CRISPR Therapeutics and Vertex Pharmaceuticals’ Casgevy, a therapy that seeks to cure two blood disorders — sickle-cell disease (SCD) and β-thalassemia. The therapy is based on gene editing technology that had won its scientists the Nobel Prize in Chemistry in 2020.Less than a month later, FDA not only approved Casgevy (exagamglogene autotemcel) for SCD, but also approved bluebird bio’s Lyfgenia (lovotibeglogene autotemcel) for the treatment of SCD in patients aged 12 and older who have a history of vaso-occlusive events (when tissues become deprived of oxygen).IX. Leqembi becomes first med to bag full approval to treat Alzheimer’sEisai and Biogen’s Alzheimer’s drug Leqembi (lecanemab) had won FDA’s accelerated approval in January. It treats patients who are in the earliest stages of the neurodegenerative disease. In July, it became the first treatment to receive full FDA approval to treat the condition.X. Bayer’s experimental anticoagulant fails late-stage trialOne of the biggest disappointments from clinical trials came when a major late-stage trial for Bayer’s experimental anticoagulant asundexian had to be discontinued due to its inadequate effectiveness. Bayer had expectations in excess of € 5 billion (US$ 5.5 billion) from this drug.  

Impressions: 2108

18 Jan 2024
Job cuts double in 2023; Pfizer, BMS, Novartis, Biogen downsize to cut costs
The year 2023 has seen considerable job cuts by biopharmaceutical companies. While layoffs have become commonplace since 2022, the exercise touched new heights this year. The reasons behind these job cuts have ranged from restructuring, drop in Covid sales, fall in quarterly revenues to shift in strategy and mergers and acquisitions.In 2022, over 100 biopharma companies had announced workforce reductions. That number has doubled in 2023. And the year has not ended as yet.In Q1 2023, the number of companies that had announced layoffs surpassed 50 and included companies like Biogen and Thermo Fisher. Between mid-April and November, this figure rose even further, with approximately 140 pharmaceutical companies disclosing workforce reductions.View Our Interactive Dashboard on Biopharma Layoffs in 2023 (Free Excel Available)Biogen, Amgen, layoff staff post mergers; low Q2 sales trigger job cuts at BMSIn our Q1 2023 update, we had mentioned that both Novartis and Biogen plan to cut jobs worldwide to save US$ 1 billion in costs. Starting November, Novartis will retrench over 100 employees at its US headquarters in East Hanover (New Jersey). Similarly, Biogen announced plans to layoff around 113 employees from Reata Pharmaceuticals’ Plano, Texas site in the US. Biogen had acquired Reata for US$ 7.3 billion in July this year, and the job cuts were announced promptly after the acquisition.Another company that announced post-merger retrenchments is Amgen, which had acquired Horizon Therapeutics in December 2022 for US$ 27.8 billion. Amgen has been aggressively cutting costs. Earlier this year, it had laid off 750 employees due to intensifying pressure on drug prices and inflation. And now, it is issuing pink slips to 350 former Horizon employees.The going has also been tough for Bristol-Myers Squibb (BMS) — it reported low Q2 revenues and had to cut its full-year forecasts as two of its top drugs, blood cancer treatment Revlimid and blood thinner Eliquis, saw a drop in sales due to competition from generics. As a result, BMS laid off 48 employees in New Jersey in May, and plans to do away with another 100-odd employees soon.Nearly a year after GSK spun off its consumer healthcare business to create Haleon, there are reports that hundreds in the United Kingdom and potentially thousands working globally for Haleon are at the risk of losing their jobs. The restructuring is likely to save GBP 300 million (US$ 393 million) over the next three years.View Our Interactive Dashboard on Biopharma Layoffs in 2023 (Free Excel Available)Pfizer, Thermo Fisher, Novavax announce layoffs due to declining Covid salesIn October, Pfizer had significantly lowered its full-year revenue forecast for 2023 due to reduced demand for its Covid products. The drug behemoth has also announced cost-cutting measures such as layoffs and expense cuts that will help save US$ 3.5 billion.During the same month, Pfizer announced plans to retrench 791 employees at its Gladstone site in the US. A month later, the company announced 800 job cuts, by reducing staff at its Kent (the UK), Michigan (the US), and Newbridge, Kildare (Ireland) sites.Thermo Fisher Scientific has been downsizing its workforce at different locations since last year. The company manufactures Covid testing kits. In our Q1 2023 update, we had mentioned that the company laid off around 500 employees across various locations in California between January 2022 and mid-April 2023.In a fresh wave of job cuts announced in November, Thermo Fisher will layoff 97 employees in January 2024. The company plans to close its facility in Alabama. Earlier in August, the company fired 205 staffers across two separate sites in Alachua, Florida, due to the relocation of development, manufacturing, and production activities from this site to their new Plainville, Massachusetts site.In November, Covid vaccine maker Novavax announced second round of cost cuts for 2023 in order to reduce spending by US$ 300 million. In May, Novavax had reduced its headcount by 25 percent to align its spending with the diminishing size of the Covid opportunity.Similarly, in June, contract manufacturer Catalent said it plans to retrench 150 employees at its Bloomington, Indiana plant. Catalent has been working closely with drugmakers to manufacture Covid vaccines and therapies, and the job cuts are part of its post-pandemic restructuring exercise.View Our Interactive Dashboard on Biopharma Layoffs in 2023 (Free Excel Available)Shifts in strategy, restructuring trigger layoffs at Takeda, PTC Therapeutics, ApellisIn May, Takeda had announced a shift in its R&D strategy, leading to 186 layoffs in Massachusetts and an additional 27 in San Diego. This announcement follows Takeda’s decision to discontinue discovery and pre-clinical efforts in AAV (adeno-associated virus) gene therapy and rare hematology.In a similar move announced in September, rare disease drugmaker PTC Therapeutics announced retrenchment of 25 percent of its workforce as part of a broader restructuring initiated in May, involving discontinuation of several early-stage gene therapy development programs to focus on high-potential R&D programs. PTC plans to complete the process by January 15. In August, Apellis announced its plan to layoff approximately 225 employees and divest two preclinical assets to achieve US$ 300 million in savings as part of a significant corporate restructuring program. This move aims to drive the growth of Syfovre, an injectable form of pegcetacoplan that received FDA approval for geographic atrophy (GA) in February.During the same month, Sage Therapeutics, a company working on novel therapies for brain health disorders, announced 188 job cuts. These were part of a restructuring plan announced soon after FDA rejected its drug Zurzuvae (developed along with Biogen) for major depressive disorder (MDD). The agency has approved the pill for postpartum depression, which is a much smaller market as compared to MDD.In September, 2seventy bio (a company spun out of bluebird bio) had announced plans to layoff about 40 percent of its workforce (i.e. axe 176 jobs) in order to lower costs and focus on the biotech firm’s cancer cell therapy — Abecma.In August, Emergent BioSolutions decided to cut 400 jobs and scale back operations at some of its facilities, in an effort to move away from its CDMO business and pivot its focus on core products, such as nasal spray Narcan and anthrax vaccines.View Our Interactive Dashboard on Biopharma Layoffs in 2023 (Free Excel Available)Our viewThe biopharmaceutical industry is still grappling with the disruptions caused by Covid. Some of the layoffs reflect a correction, as demand moves back to pre-pandemic days. The others are either a fallout of disappointing quarterly results, or the outcome of normal business restructuring and strategy shifts.While this article was going to print, there was news that Kite Pharma, a subsidiary of Gilead focusing on cell therapies, is letting go off 7 percent of its staff, or around 300 employees in order to improve operational efficiency. Similarly, another genetic medicines company Generation Bio is firing 68 employees. Both these updates follow news that FDA is investigating the  “serious risk” of cancer patients developing secondary blood cancer after undergoing chimeric antigen receptor T-cell (CAR-T) therapies. Incidentally, several startups focusing on cell and gene therapies (such as Summation Bio, Oncurus Inc, Intergalactic Therapeutics), have had to shut operations due to lack of finance.As we bid farewell to 2023, there are larger concerns of a slowdown in the global economy. For now, it seems like 2024 may not be very different from 2023. 

Impressions: 6490

30 Nov 2023
Drug shortages persist in US, Europe; Astra’s RSV therapy faces overwhelming demand
Both the US and Europe have been grappling with acute drug shortages since the start of the pandemic.Despite efforts, drug shortages are persisting and affecting a range of medicines, such as those used to manage body weight, cancer drugs, drugs that treat attention deficit/hyperactivity disorder (ADHD), antibiotics and cardiac medications. The latest to join this list is the recently approved therapy for respiratory syncytial virus (RSV) from AstraZeneca and Sanofi — Beyfortus (nirsevimab).Over the last five to six years, shortages of over 25 new molecules have been reported in the US each year. By June 2023, a total of 160 new drug shortages had been documented, but only 51 of them had been resolved. The US Food and Drug Administration (FDA) has been working closely with drug manufacturers to overcome this ongoing problem.The scenario is much the same in Europe where there has been a 20-fold increase in drug shortages over the last 20 years. Given the continued shortages of antibiotics, the European Medicines Agency (EMA) is undertaking steps to oversee critical tasks, such as monitoring and reporting drug shortages to EU countries, coordinating responses, and managing the supply and demand of medicinal products. Additionally, EMA plans to collaborate with the Health Emergency Preparedness and Response Authority (HERA) to ensure the availability of antibiotics for respiratory infections through collaborations with concerned drugmakers.View Our Interactive Dashboard on Drug Shortages in H2 2023 (Free Excel Available)Astra-Sanofi’s RSV med faces overwhelming demand; CDC prioritizes availability According to the Centers for Disease Control and Prevention (CDC), about 58,000 to 80,000 children under the age of five years are hospitalized in the US each year and up to 300 die from RSV. These numbers explain the higher-than-expected demand for AstraZeneca and Sanofi’s jointly developed RSV drug Beyfortus (nirsevimab), which has resulted in its shortage. Beyfortus is a monoclonal antibody and the first preventive option approved in July to protect infants in the US.Moreover, CDC has recommended that available doses of Beyfortus be prioritized for infants at the highest risk of severe RSV disease. The organization has also expedited the release of over 77,000 additional doses of Beyfortus and is in close contact with manufacturers to step up supplies through late 2023 and early 2024. In an interview with Reuters, AstraZeneca’s CEO Pascal Soriot said it is prioritizing the US market for additional doses of Beyfortus.View Our Interactive Dashboard on Drug Shortages in H2 2023 (Free Excel Available) Rising demand, production delays lead to shortages of diabetes, obesity medsThe US and several European countries such as Belgium, Germany and Hungary continue to face  shortages of diabetes and obesity drugs. Resulting largely from increased demand and production delays, these drugs include Novo Nordisk’s semaglutide (sold under brand names Wegovy, Ozempic and Rybelsus) and liraglutide (Victoza and Saxenda) and Eli Lilly’s tirzepatide (Mounjaro) and dulaglutide (Trulicity).So acute is the problem that Belgium has limited the use of Novo’s semaglutide and GLP-1 drugs to individuals with type 2 diabetes and weight-loss patients meeting specific body mass index  criteria. And Germany is considering restricting the export of Novo’s Ozempic.With Goldman Sachs estimating obesity drugs to attain a market size of US$ 100 billion by 2030,  both Novo and Lilly are busy expanding their manufacturing capacities. Novo is investing over Danish kroner 42 billion (US$ 6 billion) to enhance production in Kalundborg, Denmark, and Lilly will be building its first plant in western Germany for € 2.3 billion (US$ 2.5 billion) to meet the soaring demand for its diabetes and weight loss drugs. Novo has also brought Thermo Fisher onboard as a contract manufacturer for its weight loss drug Wegovy.View Our Interactive Dashboard on Drug Shortages in H2 2023 (Free Excel Available) Shortages of critical cancer drugs persist; FDA steps in to increase suppliesIn our last update, we had captured a severe shortage of cancer drugs that was deemed a national emergency by oncologists in the US. FDA's drug shortage database tells us that as of November 18, the shortage of cancer drugs persists in the US. The drugs in short supply include cisplatin, carboplatin, methotrexate, capecitabine, clofarabine, leucovorin calcium, and azacitidine.As part of its push to alleviate shortages, FDA has partnered with Chinese drugmaker Qilu Pharmaceutical and Canadian company Apotex to temporarily import cisplatin. Also, it has worked closely with manufacturers to boost production capacity.In September, the White House issued a statement that said its efforts to resolve the shortage of cisplatin have borne fruit, as the US supply of the chemo drug has been restored to nearly 100 percent of the pre-shortage levels. Recently, Accord Healthcare (the US unit of Intas) announced it has restarted the production of cancer drugs cisplatin and methotrexate.View Our Interactive Dashboard on Drug Shortages in H2 2023 (Free Excel Available) High demand, manufacturing issues lead to scarcity of ADHD drugsDuring 2020 and 2021, the US experienced a notable increase in the diagnosis of ADHD, leading to over 10 percent rise in stimulant prescriptions across diverse age groups. Record-high demand and manufacturing issues have led to a shortage of ADHD drugs, such as Takeda’s Vyvanse (lisdexamfetamine dimesylate) and methylphenidate hydrochloride (a stimulant sold under several brand names, such as Ritalin, Concerta, Methylin etc).In an attempt to ease the shortages, FDA has approved generics to Takeda’s Vyvanse capsules earlier this summer after its patent expired in August. The other drugs in short supply include statins, antibiotics, and cardiac drugs. The US has grappled with a surge in demand for liquid Amoxicillin, essential for the treatment of infections in children. Manufacturers like Teva, Sandoz, and Alembic have made the API available on an ‘allocation basis’ to meet the demand.Similarly, cardiovascular drugs like adenosine and lidocaine (used to treat arrhythmias) and medications to lower cholesterol, such as rosuvastatin and atorvastatin, are also experiencing shortages.View Our Interactive Dashboard on Drug Shortages in H2 2023 (Free Excel Available) Our viewThe geopolitical and economic situations coupled with thinning of margins in the generics industry are continuing to impact the biopharma industry. However, our analysis tells us that governments are able to address drug shortages. For instance, in the US, the list of drug facing shortages had 90 drugs on it during January to mid-June 2023. This number has come down to 68 in FDA’s latest update. Similarly, Canada has brought down shortages from 454 to 441 during the same period.However, in Europe, drug shortages have been worsening over the last six months, owing to several factors such as increased demand, inflation and geopolitical unrest. In Italy, drug shortages have increased from 423 to 541, in Norway from 320 to 370, and in Spain from 295 to 342.Let’s hope the situation improves in 2024. 

Impressions: 3054

23 Nov 2023
India continues to top FDA-registered generics facilities, sets up 20 new units for FY24
Every year, the US Food and Drug Administration (FDA) publishes the user fee amounts it will collect from manufacturers of pharmaceuticals, generic drugs, biosimilars and medical devices in the coming financial year. The fiscal year 2024 fee under the Generic Drug User Fee Act (GDUFA) was published on July 28, 2023. The facility payments list under the GDUFA has revealed that as of October 30, 2023, 1,320 facilities had paid their registration fee for financial year 2024. Out of this, 663 or 50.2 percent are active pharmaceutical ingredients (API) facilities, 395 or 30 percent are finished dosage forms (FDF) facilities, 68 (5.15 percent) are facilities that produce both APIs and FDFs, and 194 (14.7 percent) are contract manufacturing services (CMO) sites. Teva Pharmaceuticals led the list of companies by facility registrations, followed by Aurobindo Pharma and Viatris. Teva has 26 facility registrations, including 16 for FDFs, nine for APIs, and one for both APIs and FDFs. Aurobindo Pharma has 22 facility registrations, including 12 for FDFs, eight for APIs, one for CMO, and one facility that is engaged in both API and FDF activities. Viatris has registered 18 facilities, including 13 for FDFs and four for APIs, and one facility that is engaged in both API and FDF activities. Generic Drug Facilities Registered with the USFDA in FY2024 (Free Excel Available) India tops with 376 facility registrations, US comes second at 317 India continues to dominate the list of total facility registrations with the FDA — it registered 376 facilities for FY2024, including 200 API facilities and 134 FDF facilities, 21 facilities engaged in both API and FDF activities, and 21 CMO facilities.  The United States followed India with 317 facilities and China held the third position with 169 facilities. At 200, India continues to have the largest share of API facilities, which is almost equal to the API sites registered together by both China (112) and the US (76). Amongst European drugmakers, Italy leads with the 54 API manufacturing sites, followed by Spain (30) and Germany (29). The largest number of facilities for FDFs are in the US (143 sites), followed by India (134) and China (38).   Country API FDF Both CMO Total India 200 134 21 21 376 USA 76 143 12 86 317 China 112 38 11 8 169 Italy 54 2 2 18 76 Germany 29 4 1 17 51 Spain 30 9 1 4 44 Canada 7 13 12 32 France 16 1 7 24 Taiwan 10 5 6 2 23 Switzerland 15 3 4 22 Japan 19 1 20    Generic Drug Facilities Registered with the USFDA in FY2024 (Free Excel Available)  GDUFA III reauthorization and FDA user fee rates for FY 2024 The GDUFA is a law designed to speed up the access to safe and effective generic drugs for Americans and reduce the costs to the industry.  The GDUFA was reauthorized on September 30, 2022 (as GDUFA III), with provisions that came into effect on October 1, 2022, and will last until September 30, 2027. In July 2023, FDA published user fee rates for FY 2024 for prescription drugs, generic drugs, biosimilars and medical device user fee programs, as well as for outsourcing facilities. Fiscal year Facility Registrations 2013 1390 2014 1414 2015 1450 2016 1425 2017 1442 2018 1269 2019 1286 2020 1300 2021 1340 2022 1385 2023 1394 2024 1320   Last year, FDA had reduced the fee for API facilities and CMOs. However, the FY2024 fee for FDF facilities, both domestic and foreign, has gone up by over 3 percent. Similarly, the fee for large-, medium- and small-sized drug applicants has gone up by over 7 percent. Generic Drug Facilities Registered with the USFDA in FY2024 (Free Excel Available)  46 new facilities registered in FY24; India leads with 20 new units, 11 set up in China Out of the total 1,320 facilities registered for FY2024, 46 were new. Out of these, 20 were registered in India, followed by 11 in China and six in the USA. Out of the 46 new facilities, 22 are FDF facilities, including units of Alembic Pharmaceuticals (in Karkhadi, Gujarat, for injectables and ophthalmic products and in Jarod, Gujarat, for oral solids), Amneal, Aspen (in Gqeberha, South Africa, for oral solids, eye drops and sterile manufacturing), Aurobindo Pharma (in North Carolina, USA, for R&D and manufacturing of inhalation, topical and transdermal products), Novartis (in Ljubljana, Slovenia, for aseptic products, non-aseptic solutions, biosimilars, and nasal spray), Lupin (injectables), Torrent, and Granules India. There are 13 API units among the list of new registrants (including facilities of players like Global Calcium, Hikal, and Ipca Laboratories), and 11 CMO facilities (including units of Bora Pharmaceuticals and the Hetero Group).  Among the new registered CMOs is Bora Pharmaceuticals’ Mississauga (Canada) facility that produces a range of dosage forms, including oral solid dose (OSD), liquid and semi-solid therapeutics (creams and ointments). Bora had acquired this facility from GSK in 2020. In FY2024, there were 135 facilities that did not renew their registration. Amongst these were facilities owned by Akorn Pharma, which had shutdown its US operations in early 2023. In fact, 45 of the 135 facilities that did not renew their registrations were from the US. Generic Drug Facilities Registered with the USFDA in FY2024 (Free Excel Available)  Our view Over the last few years, the US drug regulator has been contending with regulatory compliance and quality issues of Indian drug manufacturers. America has also been trying to reduce its reliance on China. But the GDUFA facility payments list for FY2024 reveals that not much has changed, and it will business as usual in the coming year.

Impressions: 4965

09 Nov 2023