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.  

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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: 1668


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.  

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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: 5228


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: 2599


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: 4189


09 Nov 2023
CDMO Activity Tracker: Novo taps Patheon to augment Wegovy supply; Wuxi sets up standalone vaccine plant
The third quarter (Q3) of 2023 was marked by deals and capacity expansions in the contract development and manufacturing organization (CDMO) space. Moreover, the trend of CDMOs increasing their exposure to advanced therapies, such as biologics, cell and gene (C&G) therapies, and highly potent active pharmaceutical ingredients (HPAPIs) continued unabated. Some of the key players in the CDMO space are Lonza, Catalent, Recipharm AB, Thermo Fisher, Seqens, Curia, Siegfried, Samsung Biologics, Fujifilm Diosynth Biotechnologies, Quotient Sciences and, Piramal Pharma Solutions. View CDMO Activity Tracker of Q3 2023 (Free Excel Available) Novo taps Patheon to meet Wegovy supply; Samsung Biologics-BMS expand deal Novo Nordisk has been struggling to ramp up supplies of its popular weight-loss drug, Wegovy. Back in October 2021, there were quality issues at the Brussels facility of its key CDMO Catalent that fills Wegovy injection pens. The two companies are hoping to resolve the quality issues at the Brussels facility soon. For now, Novo and Catalent have expanded their supply agreement — Catalent’s Bloomington, Indiana plant will now fill injection pens for Wegovy. According to reports, Novo has also struck a deal with Thermo Fisher's CDMO subsidiary Patheon for manufacturing Wegovy at its Greenville, North Carolina facility. Samsung Biologics has expanded its strategic agreement with Bristol Myers Squibb (BMS) for large-scale manufacturing of the latter’s commercial antibody cancer drug substance. This drug substance will be manufactured at Samsung Biologics’ facility in Songdo, South Korea.  Polpharma has signed two agreements with Poland’s clinical-stage drug development firm — Ryvu Therapeutics — for manufacturing an active substance (RVU120) used for phase 2 clinical studies in hematology. In July, French drugmaker Biophytis signed a master agreement with Seqens to produce the active compound in Sarconeos (BIO101), Biophytis’ main drug candidate developed for three indications — severe forms of Covid-19, sarcopenia and Duchenne muscular dystrophy. A month later, Biophytis signed an agreement with Skyepharma for the production of finished product batches of Sarconeos for severe forms of Covid-19. Another CDMO, Recipharm, has partnered with start-up Ahead Therapeutics to develop a ground-breaking treatment for myasthenia gravis, a rare autoimmune disease. View CDMO Activity Tracker of Q3 2023 (Free Excel Available)  WuXi launches standalone plant for jabs in China; Bora opens new facility in Taiwan WuXi Biologics’ immunization-focused subsidiary WuXi Vaccines has launched its first standalone vaccines contract manufacturing facility in Suzhou, China. This new plant will focus on drug substance and drug product capacity for projects in various stages of development. Bora Pharmaceuticals has opened a state-of-the-art facility in Taoyuan City, Taiwan, that provides its customers access to extensive ophthalmic manufacturing services. The facility will specialize in ophthalmic products such as sterile solutions, emulsions, creams, ointments and gels. Skyepharma and clinical-stage biotech MaaT Pharma have completed construction of what will be Europe’s largest manufacturing facility for microbiome ecosystem therapies. Aurigene Pharmaceutical Services, a subsidiary of Dr Reddy’s Laboratories, will invest US$ 40 million to build a specialized development and manufacturing facility in Hyderabad (India), targeting therapeutic proteins, antibodies, and viral vectors. View CDMO Activity Tracker of Q3 2023 (Free Excel Available)  EUROAPI acquires BianoGMP; Syngene buys Stelis’ biologics facility In mergers and acquisitions, EUROAPI bought Germany-based contract manufacturer BianoGMP for €10 million (US$ 10.6 million) to strengthen its expertise in the high-growth oligonucleotide market. SK pharmteco announced it is acquiring a controlling stake in Center for Breakthrough Medicines (CBM), a Philadelphia-based cell and gene therapy CDMO. The move will expand SK pharmteco’s technical expertise, production capacity, and geographic reach. Syngene is acquiring a manufacturing facility in Bengaluru, India, from Stelis Biopharma for INR 7.02 billion (US$ 86 million), to enhance its biologics drug substance manufacturing capacity. And Sharp, a leader in pharmaceutical packaging and clinical trial supply services, has acquired Berkshire Sterile Manufacturing, a specialized CDMO focusing on sterile injectable products. View CDMO Activity Tracker of Q3 2023 (Free Excel Available)  AGC Biologics augments C&G capacities; CordenPharma upgrades peptide unit The quarter saw several CDMOs expand their facilities, including AGC Biologics, Fermion, Porton Pharma Solutions and Evonik. AGC Biologics expanded its program to provide lentiviral vector (a type of retrovirus) support for advanced therapies to drugmakers focused on rare diseases. The company added three new cell therapy suites to its Colorado facility. It also expanded its C&G therapy facility in Milan, Italy, to meet demands for GMP viral vector manufacturing projects. After bagging a potential US$ 1 billion, multi-year contract to manufacture large-volume peptide at its Colorado facility earlier this year, CordenPharma has upgraded its commercial peptide production capacity. This unit is now the world’s largest solid-phase peptide synthesis (SPPS) manufacturing facility. Meanwhile, Fermion has increased its manufacturing capacity for APIs at its Hanko site in Finland and Porton Pharma Solutions has expanded its capabilities in New Jersey, with a new 40,000-square-feet drug development facility under its US subsidiary, J-Star Research. CDMO Axplora has announced the installation of a new cGMP pilot flow chemistry unit at its Leverkusen site (Germany). Additionally, Evonik and Heraeus Precious Metals have tied up to expand their range of services for HPAPIs. View CDMO Activity Tracker of Q3 2023 (Free Excel Available)  Curia, Touchlight tie-up for doggybone DNA; MilliporeSigma opens new mRNA sites Several CDMOs advanced their messenger RNA (mRNA) drug substance facilities during the last quarter. Leading CDMO Curia has tied up with Touchlight, a company that specializes in making DNA using enzymes. This collaboration will offer Curia’s clients access to Touchlight’s special DNA vector, known as “doggybone DNA” (dbDNA), which can be used as a template for making mRNA therapies. The pact expands Curia’s existing mRNA production offerings with another differentiated source of DNA raw material that’s “immediately” available to its customers.  MilliporeSigma inaugurated two new mRNA drug substance manufacturing sites in Germany — at Darmstadt and in Hamburg. The two sites will tackle a full range of mRNA services, from preclinical to commercial-scale projects. Similarly, Ardena and RiboPro have forged a strategic alliance to provide solutions for the production of advanced mRNA and lipid nanoparticles. And American CRO and CDMO PackGene BioTech and an mRNA CDMO Kudo Biotechnology have tied up to provide customized mRNA manufacturing services for drug and vaccine development. View CDMO Activity Tracker of Q3 2023 (Free Excel Available)  Our view The start of Q4 saw leading CDMO Lonza strengthen its collaboration with a key biopharmaceutical partner to scale up the filling of antibody-drug conjugates. Moreover, Advent International and Warburg Pincus completed their US$ 4.25 billion acquisition of Baxter’s BioPharma Solutions business, which will now be known as Simtra BioPharma Solutions. Overall, the year’s developments have strengthened our belief that the global CDMO market will grow considerably in the coming years. Research and Markets puts that number at US$ 246.6 billion by 2026, up from US$ 172.7 billion in 2022.  

Impressions: 2560


19 Oct 2023
Excipient Market Overview: Biologics spur growth in lipid-based agents; Asahi Kasei opens new plant
This week, PharmaCompass analyzes the market for excipients, or inactive ingredients used in pharmaceuticals. Excipients don’t have a therapeutic effect, but serve various purposes. They are used in drugs as fillers, diluents, binders, suspending and viscosity agents, coating agents, flavoring agents, sweeteners, disintegrates, preservatives etc. Some excipients also help in drug delivery.The overall pharmaceutical excipient market is expected to grow at a compounded annual growth rate of 7.93 percent to touch US$ 13.49 billion by 2028, from US$ 9.21 billion in 2023.Excipients are of two types — organic and inorganic. Organic chemicals are compounds with carbon-hydrogen bonds (such as starch, cellulose, povidones) and inorganic chemicals are derived from minerals, metals, or other non-living sources (such as metallic oxides, calcium sulfate).The organic category dominates the market with the largest market share driven by robust demand from oral pharmaceuticals.Popular organic excipients used in pharmaceuticals are microcrystalline cellulose (MCC), lactose monohydrate, povidones, starch, and mannitol. MCC is excellent for tablet and capsule compressibility, while lactose serves as a binder and diluent. Povidones function as tablet binders and enhance viscosity in liquid forms. Starch serves as a diluent, disintegrate or binder and mannitol enhances the stability, taste, and quality of drugs.Major excipient manufacturers are Ashland Global, BASF, Evonik, DuPont, Roquette Frères, SPI Pharma, Croda International, Lubrizol, Boai NKY Pharmaceuticals, Nanjing Well Pharmaceutical, PMC Isochem, Nippon Fine Chemical, and Seqens.View our Dashboard to know more about Leading Excipient Companies (Free Excel Available)Demand for MCC surges post pandemic; Asahi Kasei, Nitika invest in new plantsSince the start of the pandemic, we have seen a surge in demand for drugs, and this has significantly boosted the demand for MCC. In January 2023, Asahi Kasei completed the construction of a ¥13 billion (US$ 98 million) pharma excipient manufacturing plant in Japan. This is Asahi’s second plant dedicated to manufacturing MCC under the Ceolus brand. This month, India-based Nitika Pharmaceutical unveiled an MCC manufacturing plant, which is India’s largest and most advanced facility with an installed capacity of 1200 metric ton.In a strategic investment, France-based Roquette acquired India-based Crest Cellulose, a manufacturer of excipients like MCC and magnesium stearate. This acquisition will help Roquette meet the increasing global demand for high-quality plant-based excipients. And in March 2023, SPI Pharma secured sole distribution rights for Cellets (MCC pellets) and TAP (tartaric acid pellets) from Switzerland-based Ingredientpharm.View our Dashboard to know more about Leading Excipient Companies (Free Excel Available) Evonik, Croda address delivery of biologics by investing in lipid-based excipientsApart from these traditional inactive ingredients, the market is witnessing an increase in adoption of lipid-based excipients that address the challenge of delivering biopharmaceuticals. Many drugmakers are actively exploring lipid nanoparticles (LNPs) as a safe and effective means of delivering biologics into target cells.The growing focus on biologics is spurring increased investments in biologic excipients.In March 2023, specialty chemicals company Evonik opened a new facility for pharmaceutical lipids at a site in Hanau, Germany. During the same month, Evonik announced it has begun construction of a US$ 220 million plant in Indiana, United States. These facilities are crucial as they will produce essential lipid-based excipients used in the manufacturing of a wide range of messenger RNA and gene therapy products. In 2022, Evonik had bolstered the global supply of pharma-grade, plant-derived cholesterol (PhytoChol), to be used in mRNA vaccines and gene therapies.In July 2023, UK-based Croda completed the acquisition of Solus Biotech. With this buyout, Croda has acquired a portfolio of phospholipids. In May 2023, Croda invested in a new 23,680 square-foot facility in Clinton County, Pennsylvania, to manufacture ingredients for drug delivery systems used in novel therapeutic drugs (mRNA vaccines and gene editing therapies). Last year, the company received around US$ 92.5 million from the UK and US government to expand its manufacturing capacity for lipid systems.In June 2023, Seqens revealed its commitment to invest € 15 million (US$ 15.85 million) in expanding its production capabilities for pharmaceutical polymers and lipids at its Aramon plant in France. This facility is poised to meet the increasing demand for lipid-based RNA delivery.View our Dashboard to know more about Leading Excipient Companies (Free Excel Available) Roquette launches excipient to stabilize probiotics; Lubrizol in deal with WeltonIn May 2023, Roquette launched its novel excipient – Pearlitol ProTec — to protect and stabilize moisture sensitive active ingredients such as probiotics. Back in November 2022, the company had also launched two groundbreaking excipients, Pearlitol CR-H and Pearlitol 200 GT, designed to address formulation challenges.In June 2023, Lubrizol announced it has licensed its novel solubility-enhancing, parenteral excipient, Apisolex, to Welton Pharma for the formulation of its pipeline drug SN-38, intended for the treatment of colorectal and related gastrointestinal cancers. Apisolex was launched in May 2022.Meanwhile, ANP Technologies' innovative nano-encapsulating polymer-based drug excipient, ANP001B, has received DMF (drug master file) acceptance. ANP001B has been effectively employed to enhance drug delivery in Fulgent Pharma’s pipeline product, FID-007 (polyethyloxazoline encapsulated paclitaxel), intended for the treatment of solid tumors in cancer patients who have undergone prior treatments.View our Dashboard to know more about Leading Excipient Companies (Free Excel Available) Post cough syrup deaths, WHO updates guidelines; FDA revises regulation In March 2023, the World Health Organization (WHO) had proposed updated good manufacturing practices (GMPs) to assist pharmaceutical manufacturers in assessing the quality of excipients. This proposal comes after episodes of cough syrups containing excipients that were contaminated with diethylene glycol (DEG) and ethylene glycol (EG), causing over 300 deaths in three countries (The Gambia, Indonesia, Uzbekistan) last year.The US Food and Drug Administration (FDA) has also undertaken significant changes in the regulation of excipients over the past three years. These revisions began with adjustments to the inactive ingredient database as part of the Generic Drug User Fee Amendments (GDUFA) reauthorization for fiscal years 2018-2022. Additionally, in 2021, FDA launched its first pilot program to evaluate the quality and toxicological data associated with novel excipients before their inclusion in drug formulations.View our Dashboard to know more about Leading Excipient Companies (Free Excel Available) Our viewInnovation and rising demand for pharmaceuticals has led to growth in the market for excipients. However, post the cough syrup deaths caused by contaminated excipients, there is pressure on manufacturers to improve quality control. This week, Reuters carried news that FDA has reprimanded 28 companies for failing to prove adequate test of ingredients used in over-the-counter drugs and consumer products for EG and DEG. With new excipients entering the market, stricter regulations will ensure that growth of these inactive ingredients comes with better quality. 

Impressions: 2254


28 Sep 2023
M&A deals surge in H1 2023, as Pfizer, Merck, Sanofi, Lilly announce buyouts
After a year when dealmaking faced several challenges, such as high interest rates and inflation and fears of a looming recession, the first half of 2023 (H1 2023) did show some signs of recovery.During this period, the biopharma industry witnessed a surge in high-profile mergers and acquisitions (M&As). Our analysis shows that total M&As during H1 2023 reached US$ 81.2 billion, as compared to US$ 89.6 billion for the full year 2022. By September 15, 2023, the total M&A deal value — at US$ 94.2 billion — had surpassed the total deal value for 2022.PharmaCompass has noticed a shift in deal trends, particularly in modalities. For instance, biologics made up for 46 percent of all deals in H1 2022, and rose to over 50 percent in H1 2023, suggesting a growing interest in biologics.Oncology and immunology are two key therapeutic areas that have seen significant scientific breakthroughs in recent years. Oncology witnessed 28 deals, worth a total of US$ 45 billion, followed by immunology with seven deals at approximately US$ 14 billion.Our data does not include deals related to acquisition of products or facilities, divestment, medical devices, diagnostics and animal health. We have considered only deals announced in H1 2023, irrespective of when these transactions were completed.View Pharma & Biotech M&A Deals from Jan. to Mid-Sept. 2023 (Free Excel Available)Pfizer-Seagen, Merck-Prometheus amongst biggest transactions of H1 2023The biggest transaction of H1 2023 was Pfizer’s acquisition of Seagen for US$ 43 billion, announced in March. The deal is part of Pfizer’s move to mitigate a hit in revenues from declining sales of its Covid-19 products and the imminent expiration of patents for some of its top drugs.As part of the deal, Pfizer will gain access to Seagen’s four approved cancer therapies, collectively generating nearly US$ 2 billion in sales in 2022. This strategic acquisition bolsters Pfizer’s existing and impressive portfolio of 24 approved oncological therapies. The second largest deal of H1 was Merck’s purchase of Prometheus for US$ 10.8 billion in April. The deal is centered around the potential of Prometheus’ candidate in phase 2 trials — PRA023 (now MK-7240) — to treat ulcerative colitis and Crohn’s disease. Merck’s CEO Robert Davis anticipates MK-7240 to be a multibillion-dollar drug.Around the same time as the Merck-Prometheus deal, Japanese drugmaker Astellas Pharma announced the acquisition of  New Jersey-based eye drug developer Iveric Bio for US$ 5.9 billion. Last month, the US Food and Drug Administration (FDA) approved Iveric’s intravitreal solution for the treatment of geographic atrophy — Izervay (avacincaptad pegol).Another significant deal announced in April was GSK’s US$ 2 billion buyout of Canada-based late-stage biopharmaceutical company Bellus Health. The acquisition is expected to further strengthen GSK’s specialty medicines and respiratory products.View Pharma & Biotech M&A Deals from Jan. to Mid-Sept. 2023 (Free Excel Available)Sanofi, Lilly, Novo Nordisk forge deals to strengthen diabetes, obesity portfoliosOver the last six months, drugmakers like Sanofi, Eli Lilly, and Novo Nordisk have beefed up their diabetes and obesity drug portfolios through acquisitions. The biggest deal in this field was Sanofi’s  acquisition of US-based Provention Bio for US$ 2.9 billion to access diabetes drug Tzield, the first and only therapy approved by the FDA to delay the onset of stage 3 type 1 diabetes (T1D) in adults and pediatric patients. This acquisition builds on a co-promotion agreement Provention Bio had signed with Sanofi in October 2022, one month prior to FDA’s approval of Tzield.In July, Eli Lilly had announced the acquisition of Versanis for a potential value of US$ 1.9 billion. The deal will give Lilly access to phase 2 drug bimagrumab, a monoclonal antibody for the treatment of obesity and cardio-metabolic diseases. In June, Eli Lilly had announced the acquisition of Sigilon Therapeutics for about US$ 344.2 million to gain access to Sigilon’s cell therapy candidate SIG-002 for the treatment of type 1 diabetes. The same month, Lilly had announced the acquisition of Dice Therapeutics for around US$ 2.4 billion in order to bolster its immunology pipeline. The deal will grant Lilly access to Dice’s experimental drugs DC-806 (for treating psoriasis) and DC-853 (for treating a variety of autoimmune and inflammatory diseases).Post the Eli Lilly-Versanis deal, Novo Nordisk announced the acquisition of Inversago Pharma for up to US$ 1.1 billion to access the company’s lead development asset INV-202, an oral cannabinoid receptor blocker. INV-202 demonstrated weight loss potential in a phase 1 trial and is currently in a phase 2 trial for diabetic kidney disease.View Pharma & Biotech M&A Deals from Jan. to Mid-Sept. 2023 (Free Excel Available)Biogen, Novartis, Sobi announce buyouts in rare disease segment; Astra buys CinCorThe rare disease segment witnessed a significant deal in July when Biogen announced the acquisition of Reata Pharmaceuticals for US$ 7.3 billion. The deal gave Reata access to rare disease drug Skyclarys (omaveloxolone), the first and only FDA-approved treatment for Friedreich’s ataxia (rare genetic neurodegenerative movement disorder) in adults and adolescents aged 16 years and older. Omaveloxolone was approved by the FDA in February 2023.In June, Novartis had announced acquisition of American biotech Chinook Therapeutics for up to US$ 3.5 billion to expand its renal portfolio. Novartis will develop and commercialize Chinook’s lead asset and late-stage drug candidates atrasentan and zigakibart for IGA nephropathy, a rare kidney disease. In May, Swedish blood disorder specialist Sobi has acquired Seattle-based CTI BioPharma  for US$ 1.7 billion, gaining access to the FDA-approved Vonjo, a novel targeted therapy for blood-related cancers known as cytopenic myelofibrosis. In January, Italy’s Chiesi Farmaceutici bought Ireland-based rare diseases drugmaker Amryt Pharma for up to US$ 1.48 billion. This deal includes Amryt’s approved drug, Filsuvez for epidermolysis bullosa, an inherited skin disease, which is approved in Europe. The same month, AstraZeneca acquired US-based drug developer CinCor Pharma for up to US$ 1.8 billion. The acquisition is expected to boost Astra’s cardio-renal pipeline with the addition of baxdrostat, a small oral molecule currently in phase 1 trial for the treatment of hypertension. Astra is optimistic about its potential in treating high blood pressure and chronic kidney disease, especially when used in combination with its blockbuster drug Farxiga for cardio-renal diseases.View Pharma & Biotech M&A Deals from Jan. to Mid-Sept. 2023 (Free Excel Available)Our viewAccording to a report by Bain & Company, global M&A value was down 44 percent in the first five months of 2023. The report cites factors such as macroeconomic and interest rate uncertainties to be complicating matters for both potential buyers and sellers. We can take heart from the fact that in comparison to the global data, M&As in the biopharma sector have actually grown in H1 2023. Going forward, there are several factors that suggest deal making in the biopharma sector will pick up further. These include factors such as attractive valuations of biotechs, rising cash reserves of big pharma coupled with cash crunch being faced by several biotechs, and patent cliffs and loss of market exclusivity threatening the revenues of several large drugmakers. In short, H2 2023 is poised to be a lot different. 

Impressions: 2750


21 Sep 2023
FDA reports 62.5% growth in new drug approvals in H1 2023; Health Canada sees drop
After a year when drug approvals by the US Food and Drug Administration (FDA) slipped to the lowest since 2016, the first half of 2023 (H1 2023) saw a 62.5 percent growth in drug approvals by the Center for Drug Evaluation and Research (CDER) as compared with the same period last year. FDA’s CDER approved 26 new drugs in 2023, up from 16 in H1 2022. Approvals of biologics by the FDA surpassed full-year totals for many of the past 20 years. Nine new biologics were approved by FDA’s Center for Biologics Evaluation and Research (CBER) in H1 2023, as against just eight for 2022.While FDA approved more drugs, authorizations by the European Medicines Agency (EMA) also increased but drug approvals by Health Canada dipped by approximately 50 percent. In the first half of 2023, EMA authorized 14 drugs, as opposed to 10 in H1 2022.  Similarly, Health Canada approved 13 drugs against 25 in H1 2022.Among the promising drugs approved in H1 2023 are Biogen and Eisai’s Alzheimer’s drug Leqembi (lecanemab), Astellas Pharma’s drug for hot flashes (associated with menopause) Veozah, AbbVie and Genmab’s blood cancer drug Epkinly and, GSK and Pfizer’s RSV vaccines Arexvy and Abrysvo, respectively.View New Drug Approvals in first half of 2023 with Estimated Sales (Free Excel Available)GSK, Pfizer’s RSV vaccines to generate over US$ 1 billion by 2028The highlight of H1 2023 has been the approval of vaccines for respiratory syncytial virus (RSV), a contagious virus that causes infections of the respiratory tract, and can cause severe illness in older adults and infants. In May 2023, FDA approved GSK’s Arexvy, respiratory syncytial virus (RSV) vaccine for people aged 60 and older, making it the first vaccine approved in the US that protects against the disease. The drug is expected to generate US$ 1.73 billion in peak sales by 2028.Weeks later, the agency approved Pfizer’s Abrysvo, another RSV vaccine for older adults. The vaccine is expected to be available in the third quarter of 2023. In late August, Pfizer also bagged an FDA nod for use of Abrysvo to prevent RSV in infants by vaccinating pregnant women. The drug is expected to generate US$ 1.31 billion in peak sales by 2028.View New Drug Approvals in first half of 2023 with Estimated Sales (Free Excel Available) Leqembi, Veozah, Epkinly likely to join ‘over US$ 1 billion club’ by 2028In March, the US health regulator suggested stricter trials for accelerated approval of cancer drugs. The proposed recommendation followed criticism over the approval of Biogen and Eisai’s Alzheimer’s treatment Aduhelm through this pathway in June 2021.Contrary to this stand though, FDA had approved another Alzheimer’s drug from Biogen and Eisai — Leqembi (lecanemab) — through the same pathway in January 2023. Leqembi is an amyloid beta-directed antibody indicated for the treatment of Alzheimer’s disease. The drug is expected to generate US$ 1.9 billion in peak sales by 2028. Later in July, FDA expanded the accelerated approval of lecanemab to a traditional approval for early-stage Alzheimer’s disease.The US regulator approved several potential blockbuster drugs during the month of May. It granted full approval to Pfizer’s Covid-19 oral antiviral pill Paxlovid (nirmatrelvir and ritonavir) during the month, which had been granted an emergency use authorization during the heydays of the pandemic. Paxlovid is the first oral antiviral pill for Covid-19. With the pandemic behind us, Paxlovid’s sales have been waning, though it is still projected to yield approximately US$ 5.5 billion in sales by 2028.The other important drug approved in May is Japanese drugmaker Astellas Pharma’s oral drug Veozah (fezolinetant) for the treatment of moderate to severe vasomotor symptoms (VMS), or hot flashes associated with menopause. The drug will cost US$ 550 for a month’s supply. Veozah is expected to generate US$ 1.9 billion in sales by 2028.FDA also granted accelerated approval to AbbVie and Genmab’s blood cancer therapy Epkinly (Epcoritamab-Bysp) in May. It has bagged approval to treat patients with diffuse large B-cell lymphoma (DLBCL), and is likely to emerge as a US$ 1.1 billion product.View New Drug Approvals in first half of 2023 with Estimated Sales (Free Excel Available) Sarepta, Biomarin’s gene therapies bag FDA nod; Lilly’s Jaypirca okayed for lymphomaIn June, FDA approved Sarepta’s Elevidys and Biomarin’s Roctavian. Elevidys bagged accelerated approval in Duchenne muscular dystrophy (DMD) patients aged four to five years. This is the first gene therapy approved by the FDA for the treatment of certain patients with DMD. Elevidys is expected to generate US$ 3.36 billion in peak sales by 2028.BioMarin’s one-time gene therapy – Roctavian – has been approved by the FDA to treat severe hemophilia A, a rare bleeding disorder. Priced at US$ 2.9 million, Roctavian is the first gene replacement therapy to be approved for the condition. Roctavian is expected to generate US$ 1.43 billion in peak sales by 2028. This approval follows another approval granted in November 2022 for the first gene therapy to treat adults with hemophilia B — CSL Behring and uniQure’s Hemgenix.In January, Lilly’s Jaypirca (pirtobrutinib) bagged FDA nod, thereby becoming the first and only non-covalent, BTK Inhibitor for the treatment of adult patients with relapsed mantle cell lymphoma which did not respond to other BTK Inhibitors. Jaypirca is expected to generate US$ 0.91 billion in peak sales by 2028.In March, FDA approved Pfizer’s Zavzpret (zavegepant) as the first and only calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray for the acute treatment of migraine. Zavzpret is expected to generate US$ 0.649 billion in peak sales by 2028.Another important FDA approval was granted to GSK’s drug Jesduvroq — it is now the first oral treatment for anemia caused by chronic kidney disease in adults who have been on dialysis for at least four months.View New Drug Approvals in first half of 2023 with Estimated Sales (Free Excel Available) FDA rejects Lilly’s donanemab, Alvotech/Teva’s Humira biosimilarIn January, when the FDA had approved Leqembi, the agency had rejected Eli Lilly’s bid for an accelerated approval pathway for its experimental Alzheimer’s disease drug donanemab. The agency had cited a lack of participants who received continuous treatment with donanemab for at least 12 months as the reason for its decision. However, Lilly announced positive late-stage trial results on donanemab in July — it slowed cognitive decline by 35 percent compared to a placebo in a late-stage trial. An FDA decision on the drug is likely around 2023-end or in early 2024.Similarly, FDA turned down Lilly’s mirikizumab for the treatment of ulcerative colitis. The agency also rejected a BLA for Eli Lilly’s ulcerative colitis drug mirikizumab over manufacturing concerns. Besides these, FDA also rejected Alvotech/Teva’s Humira biosimilar — AVT02 — for a second time this year.View New Drug Approvals in first half of 2023 with Estimated Sales (Free Excel Available) Our viewAfter the pandemic, business is back to normal at the FDA. The number of CDER approvals in the first half of this year are approximately 70 percent of the approvals in 2022. We anticipate more approvals in the upcoming months. If the FDA sustains this pace, approvals this year could potentially double those of the previous years. 

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31 Aug 2023