Mike Hennessy Jr. is the President and CEO of 

Mike Hennessy Jr.

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Pharmaceuticals are entering a transition into a far more complex era of patient therapies, and patient segmentation. It will not be an easy process. It’s an evolution long in the making and welcomed for not only improved treatment outcomes, but also for increasingly realistic “cures”. In such a tightly regulated space, where large financial investments are also required, many unwilling stakeholders will be swept along with this rising tide of new medicines. Who would have seriously considered larger-scale three-dimensional printing of medicines five years ago, or marrying messenger RNA delivery methods with chimeric antigen receptor therapies for reconfigurable patient specific antigen profiles, within the same patient, over the span of a month?

To keep this surging tide heading into workable spaces without swamping all systems, international bodies, such as the International Council for Harmonisation and the World Health Organization, are going to have to be relied on to perform much of the heavy lifting. New financial cooperation models, some of which were trial ran during the COVID-19 pandemic, must also be implemented for consolidated gains to remain real.

With these advances rolling in at a more rapid pace than ever before, our coverage of the pharmaceutical space must also evolve. This year, we have increased our coverage of the daily news, to provide insight at a greater pace. The brand has also rededicated to video coverage, to provide insight from the experts on the frontlines of these advances. Along with these changes, we have amped up our conference coverage, to provide key advances and learnings from major meetings throughout the year, like our coverage from the 11th International mRNA Health Conference and CPHI Barcelona. All these latest insights can be read at 

As we eye up trends and opportunities for 2024, we are truly excited for the fruits of the future. There is so much awaiting us, and we can be guaranteed that the new medicines about to be manufactured, stored, delivered, and received will be more efficacious than ever and worth the efforts. And that is something worth holding on to, something to be proud of.

When referring to this article, please cite it as Hennessy, M. The Dislocation of Progress. 

Articles

Pharmaceuticals are entering a transition into a far more complex era of patient therapies, and patient segmentation.

The Dislocation of Progress

As of mid-October 2023, there were 9342 clinical trial studies targeting COVID-19 (1). This is alongside 12,086 patents that relate to COVID-19 (2). Messenger RNA (mRNA) clinical trials, however, stand at only 483, with 112 related patents. mRNA was the talk of the industry during October 2023, as Katalin Karikó and Drew Weissman were awarded the Nobel Prize in Physiology or Medicine for their work in mRNA vaccines against COVID-19.
In an interview with Pharmaceutical Technology®, Laks Pernenkil, Principal and Practice Leader, US Life Sciences, Deloitte, pointed to “an emphasis coming out of the pandemic on supply resilience … with all the ups and downs around the supply of raw materials, there has been significant focus on ensuring patients are not affected by supply shortages, part of the anxiety has manifested around inflation [rising costs] of raw materials.” Pernenkil also drew attention to increased digitalization as improving process design, supply performance, and eventually, profits (3).
At the other end of the spectrum, discovering new types of drugs and therapies, the top five pharmaceutical companies’ investments in R&D in 2022 were Roche with $14.78 Billion, J&J $14.14 billion, Pfizer $12.38 billion, Merck $11.84, and BMS $10.02 billion, ranging between 15% to 30% of income (4). Such investment speaks of self-confidence and perhaps aligns with increasing trust in the newest modalities, including mRNA approaches.


NIH. https://clinicaltrials.gov. Clinical trials.gov (accessed Oct. 12, 2023).

World Health Organization, WHO’s Covid-19 Response Timeline (accessed Oct. 12, 2023).

Playter, G. The Era of Digital Data in Bio/Pharma Manufacturing. 

Statista. Leading 50 Global Pharmaceutical Companies by Prescription Sales and R&D Spending in 2022. 

When referring to this article, please cite it as Hennessy, M. Capitalizing on Success. 

Industry investments indicate increasing trust in the newest modalities, including mRNA approaches. 

Capitalizing on Success

 article (1) outlined that new therapeutics and breakthroughs in neurosciences have lagged far behind oncology or infectious diseases. In Alzheimer’s disease, despite knowing for decades that p-tau and amyloid plaques are established hallmarks, current armaments are severely constrained to drugs that ameliorate disease progression in people living with early Alzheimer’s disease, such as Aduhelm and Leqembi, or drugs that tackle memory and cognitive decline, such as Cholinesterase inhibitors such as Aricept, Exelon, and Razadyne, and Glutamate regulators. All have efficacy questions swirling, while some also have considerable side effects issues, including attendant brain swelling problems (2), and therefore, “current therapy using anti-plaque approach might not be the best option to tackle these diseases” (1).

Neurons are comparatively long-lived cells but are destroyed by Alzheimer’s. Today significant progress can be relayed based on the underlying biology of how this happens. Professor Bart De Strooper, group leader at VIB-KU Leuven Center for Brain and Disease Research, contends, “Our study sheds light on the previously murky waters of Alzheimer’s disease, revealing a potential key player in neuronal loss—an RNA gene called MEG3, and the process of necroptosis” (3). This study contrasted mouse neurons to human, which resisted cell death by comparison, which if analyzed and understood, could provide a protective treatment avenue. As the study itself emphasizes, “Down-regulation of MEG3 and inhibition of necroptosis using pharmacological or genetic manipulation of receptor-interacting protein kinase 1 (RIPK1), RIPK3, or mixed lineage kinase domain-like protein (MLKL) rescued neuronal cell loss in xenografted human neurons” (4). Meaning the effects of the disease, including neuronal tangles and necroptosis, was successfully reduced.

It has been a long wait, but for Alzheimer’s at least, this is the beginning of renewed hope.

Necdina, M. What is Wrong with the Neuroscience
Drug Market? 

UK Research and Innovation. New Study Discovers How Neurons Die in Alzheimer’s Disease. UK Research and Innovation, 

Balusu, S.; Horre, K.; Thrupp, N.; et al. MEG3 Activates Necroptosis in Human Neuron Xenografts Modeling Alzheimer’s Disease. Science, 

When referring to this article, please cite it as Hennessy, M. Renewed Hope for Alzheimer’s. 

Renewed Hope for Alzheimer’s

From a pure business perspective, while equal in many respects to computer chip manufacturing, the pharmaceutical industry pulls ahead because it does not experience the same high amplitude boom and bust periods. This is attractive to investors. We have noted, however, that many key products face looming patent expiration. Prices, especially for some new single dose treatments, can be eye-wateringly high and that for an increasing number of patients the traditional insurance cost-to-benefit model needs reinvention.

Despite these deeply entrenched problems, business prospects continue to shine, fueled in part by a new sense of discovery and remarkable invention. An era of personalized cancer vaccines could be at hand, and the general public is now aware of the efficacy of certain weight loss drugs which has evolved (in some cases) from former diabetes treatments to work effectively in both curbing weight but also in mitigating cardiovascular and related sequalae.

As we currently stand, the prototypical institutional investor, such as retirement fund or investment banks, will continue to back our industry with their (or other peoples’) dollars. But a key emerging trend, to replace an approximate loss of $200 billion by blockbusters to generics, will be pharmaceutical companies themselves reinvesting in their own future through mergers and acquisitions but also in increased R&D activities. Fresh from their 44th annual healthcare conference, Goldman Sachs forecasts that, “The pharmaceutical industry will need growth, and is sitting on a tremendous amount of cash. The firepower that we’ve calculated—i.e., cash plus modest leverage—amounts to $700 billion dollars globally. The baseline expectation is that there is going to be continued M&A, though there has been increased focus recently on regulatory uncertainty, particularly as it relates to larger deals” (1).

On the smaller scale, several companies were held recently up as exemplars for investor success, which includes the 324% one-month trailing total return (TTR) for Madrigal Pharmaceuticals (good Phase III results for treatments for non-alcoholic steatohepatitis), 312% TRR for Pliant Therapeutics (reporting positive Phase IIA results for oral medication to treat idiopathic pulmonary fibrosis), and 271 TTR for Reata Pharmaceuticals, which works on novel treatments for neurologic disorders and chronic kidney disease (2).

1. Haider, A. Pharmaceutical Companies Have $700 billion for Acquisitions and Investment. Intelligence Articles, Goldman Sachs. July 6, 2023.
2. Bolton, N. Top Pharmaceutical Stocks for Q2 2023, May 2023, Investopedia.

When referring to this article, please cite it as Hennessy, M. Billions of Reasons to be Buoyant. 

Pharma's ability to continually reinvent itself will be critical in growing future business operations.

Billions of Reasons to be Buoyant

In June 2021, the Biden–Harris administration announced a task force to address “short term supply chain discontinuities” (1). This included strengthening Executive Order 13944, a list of essential medicines, medical countermeasures, and critical inputs (2). A report published in May 2022 highlights fundamental pillars one would expect (3).

A proposed bill by US Senator Gary Peters (MI), Chairman of the Homeland Security and Governmental Affairs Committee, building off several reports he released in the past few years, proposes to assess national security vulnerabilities in the pharmaceutical supply chain by the Mapping America’s Pharmaceutical Supply (MAPS) Act. This database will include key information about critical drugs such as the country of origin and quantity so supply chain weaknesses can be identified (4). While this might seem duplicative of other database systems such as North American Industry Classification System codes, it can be seen as part of a macro trend for government, to take further action in an already highly regulated industry. The Inflation Reduction Act (IRA) and the National Biotechnology and Biomanufacturing Initiative are cut from the same cloth.

Rumors have swirled about an under-the-radar White House initiative to gather pharmaceutical supply feedback to present potentially radical options. On this initiative, but specifically commenting on generics, Elisabeth Reynolds, a Massachusetts Institute of Technology lecturer and former special assistant to Biden for manufacturing and economic development at the National Economic Council, said, “There’s a lot of resistance in the industry to more transparency or anything that requires more cost in this low-margin business. We have to find ways to provide incentives to invest in quality, or put in place requirements to make them responsible for quality” (5).

Tom Kraus, VP government relations for the American society of health-system pharmacists, strongly supports MAPS, saying, “By requiring HHS to coordinate with other agencies and the private sector to map the pharmaceutical supply chain, threats to the US pharmaceutical supply chain can be identified and addressed before they place patients at risk” (5).

1. White House. FACT SHEET: Biden-Harris Administration Announces Supply Chain Disruptions Task Force to Address Short-Term Supply Chain Discontinuities. 

2. FDA. Reports, Executive Order 13944 List of Essential Medicines, Medical Countermeasures, and Critical Inputs. August 2020.

3. The Advanced Regenerative Manufacturing Institute (ARMI). 

Essential Medicines Supply Chain and Manufacturing Resilience Assessment

. BioFabUSA Roadmap Reports, Special Reports.

4. Senator Gary Peters Office, Peters Introduces Bipartisan Bill to Assess National Security Vulnerabilities in the Pharmaceutical Supply Chain. Press Release. July 20, 2023.

5. Griffin, R.; Edney, A.; Swetlitz, I. Secret White House Team Tackles Drug Shortages, Quality Woes. 

When referring to this article, please cite it as Hennessy, M. 
Supply Chain Securities. 

Mapping America’s Pharmaceutical Supply (MAPS) Act aims to establish a database including key information about critical drugs so supply chain weaknesses can be identified.

Supply Chain Securities

Prescription drug patent exclusivity was extended during Hatch-Waxman Act’s convoluted negotiations to increase generic drug access and overall drug affordability. Later, around 2009, part of the prescription price increase allowance and extension argument for biologics was based on what was termed a “looming patent cliff.” Patent protection is now 20 years from date of filing in the United States, but market exclusivity appears to average a little over 13 years in practice (1). Following Hatch–Waxman, the generic products’ share of total prescriptions in the US increased from 36% in 1994 to 90% in 2019 (1). Loss of income due to lower pricing of generics estimated at $185 billion was evenly balanced by price hikes for prescription drugs of $187 billion (2). This helped create the conditions we face today where once again there is a prescription drug price crisis because 10% of prescriptions have an average cost of $20 a day and account for 80% of all prescription drug spending, despite the fact that (largely due to Hatch-Waxman) 90% of prescriptions are generics that cost on average, $1 a day (2). 

To revisit the cost issue, President Biden signed the Inflation Reduction Act (IRA), while pharmaceuticals reportedly face, once again, a looming patent cliff (3). With regard to IRA, biopharma executives describe the Medicare drug price negotiation process “as basically enforced price fixing on certain established medicines and that it will affect how companies allocate capital and force hard decisions on investments in the very costly process of drug testing and production” (4). 

However, at the 2023 BIO conference in Boston, FDA Commissioner Robert Califf stated that drug prices are too high, and that “FDA officials are providing technical assistance to their counterparts at the federal Centers for Medicare & Medicaid Services as they prepare to negotiate drug prices with companies for the first time” (5). On limiting reimbursements for accelerated clinical trials, Califf went on to say, “‘sounds like common sense to me’ for government health insurers to pay less for drugs that haven’t yet been fully approved. ‘If I had a basketball that’s probably going to stay inflated and it looks pretty good in the store but we don’t really know, you wouldn’t really pay the same as you would for a first-rate basketball’ guaranteed to stay firm” (5).

1. Grabowski, H.; Long, G.; Mortimer, R.; and Bilginsoy, M. Continuing Trends in U.S. Brand-name and Generic Drug Competition. 

. August 2021. Taylor and Francis online. 

2. Engelberg, A. Unaffordable Prescription Drugs: The Real Legacy of the Hatch-Waxman Act, 

4. Wechsler, J. Biden Hits Drug Prices for Boosting Health Care Costs. 

5. Weisman, R. FDA Chief’s Unwelcome Message to Biotech Execs: Prices of Drugs Are Too High. 

When referring to this article, please cite it as Hennessy, M. Drug Pricing’s Static Changes. 

The debate surrounding drug pricing changes rages on.