In a world of change, big pharma remains a constant

  • Pfizer, Roche and Novartis top the pharma table – and are set to stay there until at least 2022.
  • Novo Nordisk predicted to deliver the greatest return on investment.
  • But cell and gene therapies, plus AI, digital tech will disrupt pharma business model.


Analysts casting their eyes forward to 2022 see big pharma maintaining its position in the sector, protected by vast war chests and ready to pounce on any newcomer that shows promise. Here pharmaphorum’s Andrew McConaghie crunches the numbers.

In June 2017 Evaluate Pharma unveiled its forecasts for what it believed the pharmaceutical industry would look like in 2022. This is, of course, five years away, which can seem like a lifetime in our increasingly high-speed and unpredictable world.

It is just 10 years since the iPhone was launched, but its influence has been enormous, creating a truly interconnected, digital life for people in all parts of the globe, and also making the once also-ran Apple into the world’s biggest corporation.

Probably the closest equivalent in pharma is Gilead, which has witnessed a meteoric rise thanks to the launch of its groundbreaking hepatitis C drug Sovaldi.

It was approved just three-and-a-half years ago (December 2013), and has made a lasting impact on pharma and healthcare systems. It not only brought a cure to millions of patients for the first time, but it has also altered the relationship between the industry and payers forever (though not necessarily in pharma’s favour).

There is undoubtedly further ‘disruptive innovation’ on the horizon, but how will it affect the way new medicines are discovered, developed and marketed?


Could anything come along and make these companies extinct overnight, like a giant technological meteorite wiping out pharma dinosaurs?

Certainly, Evaluate Pharma doesn’t predict any great changing of the guard at the top of the industry.  Just look at the three companies predicted to lead the sector in 2022, and consider how long they have been around: Pfizer was established in 1849; Roche was set up in 1896, and Novartis, tipped to be number one in five years’ time, can trace its roots back to two originator companies, one established in 1859, the other in 1886.

This triumvirate currently sits atop the pharma sector table, and analysts like Evaluate see no reason to believe they won’t be there in five years’ time.

There are a few simple reasons for this: these companies have proven themselves adept at adapting to changing environments, and have huge war chests to simply buy themselves out of trouble when the need arises.

But of course, that’s the nature of change: sometimes, you just don’t see it coming or, even if you do, you can’t get out of the way fast enough.

The most notable example of this in recent corporate history is Kodak, the film and photographic company, which had its roots in the chemicals business closely related to pharma, and was established in the same era, in 1888.

Kodak failed to realise that digital photography would sweep away the old analogue technology within a very short space of time, and paid the price when it filed for bankruptcy in 2012.

So far, no big pharma company has come anywhere near to bankruptcy, and they remain among the most secure firms in any sector.

Most of the biggest companies have, in addition to their huge financial firepower, some diversification to counterbalance the high risk/high rewards R&D-based game.

Worldwide prescription drug sales (2016-2022): Top 20 companies and total market


Pfizer and Novartis both have generics/biosimilars arms, while Roche has a diagnostics division (the latter currently a commercial slow-burner, but one which is likely to play an increasingly important role in healthcare).

Indeed, the only company expected to sink rapidly down the rankings over the next five years is Gilead. That’s largely based on the fact that it has been (in part) a victim of its own success in hep C, and won’t be able to sustain the surge in revenues it achieved in 2014 and 2015.

The company’s management are currently reticent about spending its $31 billion in cash funds, and Evaluate Pharma thinks this and a tailing-off in hep C revenues will see it fall a full nine places in the industry rankings.

Of course, Evaluate hasn’t factored in the possibility of Gilead finally losing its inhibitions and making a ‘mega merger’ or another canny Pharmasset-type acquisition, both of which remain possibilities.

Success in pharma is certainly not directly tied to a diverse portfolio – with its specialisation in diabetes, Novo Nordisk is probably the top 20’s most focused/exposed company, and is expected to rise three places, to 14th, by 2022.

There is growing talk of a cure for type 1 diabetes being a possibility in the next 10-20 years thanks to cell therapy research, but the sheer volume of patients requiring insulin and other diabetes products means Novo’s business model won’t be under threat for some time yet.

Indeed, Evaluate predicts that Novo will deliver the greatest return on investment in R&D, deals and M&A for the whole sector.

Cell and gene therapies

However, there is no doubt that revolutionary cell and gene therapies will have established themselves by 2022, and their long-term impact on pharma and healthcare systems could be far, far greater than that of Sovaldi.

Top 20 most valuable R&D projects (ranked by Net Present Value – NPV)


That’s because many of these drugs could potentially offer a one-treatment cure for cancers and rare genetic conditions, which are intractable and often terminal conditions today. Already filed with the FDA, the rival CAR-T drugs from Kite Pharma (axicabtagene clloleucel) and Novartis’ CTL019 are both tipped to be multi-billion dollar earners in cancer by 2022, though this will depend on just how many patients can achieve a long-term remission or a cure.

A handful of other companies, such as bluebird, Spark Therapeutics and Sangamo are all developing what could be curative gene and cell therapy treatments across a range of genetic diseases.

These drugs are expected to command extremely high prices – up to $1 million for a single, one-off treatment to cure patients. Such products will test the business models of pharma, and the resources of healthcare systems, enormously.

However, it’s by no means assured that these new cell and gene therapy companies will muscle in to the big pharma clique – bluebird, Spark Therapeutics and Sangamo have strategic deals with an existing big pharma company (both Pfizer in the second two cases) and these could swoop to acquire a firm once its candidate has proven its value.

FDA is Advancing the Goals of the Orphan Drug Act

Three months ago, FDA committed to fully eliminate a backlog of about 200 orphan drug designation requests that were pending review with FDA, and to implement policies that would require FDA to respond to all new designation requests within 90 days of receiving them. Moreover, the agency pledged to never allow a backlog of these designations to accumulate again.

At that same time, I said that we may pursue other policies that we believe would enable us to better advance the goals of the Orphan Drug Act (ODA). All of these commitments were part of a new Orphan Drug Modernization Plan that we announced on June 29th.

I’m pleased to update you on our progress in meeting each of these objectives.

First, owing to the dedicated efforts of the orphan drug designation team who oversee the Orphan Drug Designation Program, the first of these goals has been fully achieved. Reviews of all orphan drug designation requests older than 120 days were completed on August 28th. This was well ahead of the September 21st deadline that we had set for ourselves under our orphan drug plan. The achievement is hopeful news for those with a rare disease, defined as a disease which generally affects fewer than 200,000 people in the United States. Companies that receive orphan drug designation for their product qualify for various incentives including tax credits for clinical trial costs, relief from prescription drug user fees and the potential for seven years of marketing exclusivity after the drug is approved.

Second, we’re putting in place new policies to improve the efficiency of our review process to ensure that we meet our new 90-day mandate to prevent new backlogs.


To do this, FDA will pursue a range of process improvements. Among them: we’ll reorganize our review staff to improve workload efficiencies and to better leverage the expertise across FDA’s medical product centers. We’ll also use lean management principles to design a new process map that’s based on an assessment of sources of delay or redundancy and metrics for measuring success. This new workflow will outline a more efficient process that eliminates redundancies and delays that don’t add value. We’ll share this map with you in the fall.

Finally, we’re going to be taking new policy steps to make sure that the incentives offered by the ODA are granted by FDA in a way that’s consistent with the manner Congress intended. To that end, FDA will soon hold a public meeting to get input on complex scientific and regulatory issues such as those raised by molecularly targeted drugs and biologics and the appropriate application of orphan incentives in that paradigm. As part of this process, FDA will also be examining aspects of how the agency grants designations, to make sure they continue to reflect current science and drug development and the goals intended by Congress.

For all the success of the ODA, there’s been criticism that some sponsors are using designations as a way to sidestep other important public health goals set out by Congress. We need to make sure our policies take notice of all of these new challenges and opportunities.

FDA plans to advance certain guidance documents and other policies to address these issues. One guidance document will close a loophole that allows sponsors to avoid an obligation to study drugs in pediatric indications. This circumstance arises if sponsors received an orphan designation for a pediatric subtype of an otherwise common and non-orphaned adult disease.

The longstanding practice of allowing pediatric subpopulations of common diseases to be designated as orphan conditions was intended to promote pediatric drug development. It pre-dated the implementation of the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act (PREA), two laws that were specifically aimed at promoting more pediatric studies.

Now, instead of instigating more pediatric research, the granting of the orphan designation in the pediatric subpopulation can have the opposite effect. It can allow sponsors to sidestep pediatric study requirements that are part of other laws aimed at promoting this same research.

Consider a condition like inflammatory bowel disease. A drug may be approved to treat the large population of adults with the condition. Then the same drug may be granted an orphan designation to treat the much smaller population of a subset of children suffering from the same condition.

But once a drug receives an orphan designation for a pediatric population of the adult disease, the drug then becomes statutorily exempt from the requirements of PREA. This occurs even in cases where the sponsor never goes on to develop the drug for this pediatric use. These PREA requirements could have required the sponsor to study the drug for this or other uses in children. By granting the drug a pediatric orphan designation, it means the drug never has to actually be studied for a pediatric use. It’s a loophole that is in direct opposition to what Congress intended.

Nobody envisioned this unintended conflict between the original ODA and the provisions outlined in PREA. In effect, by letting sponsors designate pediatric subpopulations of drugs intended to treat adult diseases, the drug makers receive an unintended “free pass” from having to study drugs in these or other pediatric uses. Thus, rather than ensuring more pediatric research, as Congress envisioned, we can end up with fewer pediatric studies. FDA will soon issue a draft guidance document that’s aimed at closing this inadvertent loophole.

Taking these and other steps to modernize our stewardship of the ODA is imperative. Science is giving us new opportunities to use the tools offered by the ODA to advance innovation in more areas of medicine where patients have few, if any options. At the same time, the demands on FDA’s orphan drug program continue to grow. We need to make sure the policies governing how we implement these key provisions are modern and efficient.

The number of requests received by FDA under the Orphan Drug Designation Program has steadily increased over the past five years, rising to 568 new requests in 2016. This is more than double the number of requests received in 2012.  Patients with rare disease often have limited or no treatment options. We want to maximize new opportunities for patients.

FDA will continue to make full use of tools provided by Congress to apply incentives for the efficient development of rare disease therapies, and for activating more pediatric research. These steps will help us achieve our ultimate goal: to facilitate the development of safe, effective innovations that have the potential to meaningfully impact rare diseases.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration

Apple CEO pledges to put patients’ health before profits

Apple is looking at the broader healthcare ecosystem and not just those ventures that can make the firm money, according to CEO Tim Cook. 



The remarks were made in an interview with Fortune, a day before the company launches its latest iPhone model.

Speaking on a variety of subjects, from the ever-evolving Apple Watch to its attempt to aid in the clinical research industry with ResearchKit, Cook hinted toward a busy future in healthcare for Apple.

“There’s much more in the health area. There’s a lot of stuff that I can’t tell you about that we’re working on, some of which it’s clear there’s a commercial business there. And some of it it’s clear there’s not. And some of it it’s not clear. I do think it’s a big area for Apple’s future.”

But the overarching theme of Cook’s answers centered on Apple being different to competitors in that it focuses on what will help people, rather than what will make the company money.

One of the biggest opportunities to do so is expanding into the healthcare industry, explained Cook:

“If you look at it, medical health activity is the largest or second-largest component of the economy, depending on which country in the world you’re dealing with. And it hasn’t been constructed in a way where the focus at the device level is making great products from a pure point of view.”

He added: “The focus has been on making products that can get reimbursed through the insurance companies, through Medicare, or through Medicaid. And so in some ways we bring a totally fresh view into this and say, ‘Forget all of that. What will help people?’”

Cook’s biggest example of exactly that is the iPhone based health research tool, ResearchKit. He said: “We put out ResearchKit and made it a source so that people could run enormous-sized studies,” he said. “There’s no business model there. Honestly, we don’t make any money on that. But it was something that we thought would be good for society and so we did it.”

Although plenty has been speculated about the Apple Watch – with potential features allowing diabetes patients to monitor blood sugar – little has been revealed in the way of the new iPhone 8 and iPhone X smartphones.

The announcement later today could include the rumoured Apple take on electronic patient records, plans of which were leaked by CNBC earlier this year.

Facebook just held a breakfast to promote its ‘clinical trials strategy’ to drug marketers

  • Facebook brought drug marketers together to educate them on targeting consumers.
  • The company is going after an industry that’s rapidly increasing its digital ad spending

fb clinical trial.jpg

On Thursday, the company’s New York-based health unit hosted an invitation-only breakfast for pharmaceutical marketers to learn about targeting users for their clinical trials.

CNBC viewed a copy of the invitation, which asked participants to attend a presentation on the company’s “new clinical trials strategy.”

Facebook is already widely used by clinical trial recruiters. The sector is a massive revenue opportunity for the company. Research firm eMarketer estimates that pharma and health-care marketers will spend $3.1 billion on digital advertising by 2020, up from $1.9 billion last year.

According to a person who attended Thursday’s event, Facebook detailed how drug marketers can and can’t target users. The source requested anonymity because Facebook did not make the details public.

Facebook’s health team explained that users can’t be targeted based on health conditions like insomnia. This is not limited to clinical trials.

Marketers can target people by demographics and their expressed interests, or likes. Millions of health groups have organically popped up on Facebook for people with a variety of health conditions, though marketers can’t use that data in their outreach.

Some drug companies have been reluctant to use Facebook due to concerns that patients will share sensitive information like medical side effects and adverse events. Pharmaceutical companies are required to monitor and report these comments.

This wasn’t Facebook’s first event for drug marketers. CNBC reported in May that the company was hosting a summit the following month to pitch its platform as an alternative to traditional television and print media ads.

Smartphone app looks to tackle US opioid crisis

A smartphone app could help improve pain and addiction management associated with America’s ongoing opioid crisis.



According to the National Institutes of Health, more than 25 million – or over one in 10 – Americans experience pain daily.

But overreliance on opioid-based prescription painkillers has created a national crisis: around half of the 33,000 Americans who died from opioid drug overdose in 2015 did so with a prescription treatment.

Consequently, regulations on pain relief opioids have tightened, making it more difficult to access opioids from a patient’s point of view, but harder for providers to know what to safely prescribe their patients.

Launched by US firm Avella, the Pain and Addiction Management Mobile App attempts to address this challenge, providing US health providers with crucial information about opioids.

This includes changes to regulations, clinical information about opioids, and prescribing guidelines from bodies like the Centers for Disease Control and Prevention.

Also included is an ‘opioid converter’ function which can inform providers how best to transition a patient from one medication to another while maintaining safety and efficacy of treatment.

“Prescribing pain medications has always been a difficult task given the safety risks, addiction potential and side effects of certain powerful narcotics,” said Eric Sredzinski, executive vice president of Clinical Affairs and Quality Assurance Program Director for Avella. “Today it is more challenging than ever, which is why we’re looking to support our provider partners as they help patients manage chronic pain while preventing the devastating impact of opioid addiction.”

In response to the opioid crisis – which President Trump has labelled “a national emergency” – the FDA is looking to bring more non-narcotic pain relief medications to market.

This includes Lilly and Pfizer’s tanezumab for chronic low back pain which was granted fast-track designation in June.

In an unprecedented move, the agency asked Endo to remove its painkiller Opana ER from the US market over fears it was fuelling the opioid crisis. Endo withdrew its painkiller in July.

Summit Therapeutics antibiotic delivers encouraging clinical trial results

A phase II clinical trial pitched Summit’s ridinilazole against a specialist (narrow-spectrum) drug, fidaxomicin


Summit Therapeutics PLC’s (LON:SUMM, NASDAQ:SMMT) next-generation antibiotic scored well in a head to head with the existing treatment for Clostridium difficile infection (C.difficile).

A phase II clinical trial pitched Summit’s ridinilazole against a specialist (narrow-spectrum) drug, fidaxomicin. The data revealed that both reduced the abundance of C.difficile. However, ridinilazole had “markedly less” impact on the gut microbiome.

Body’s ecosystem

The ecosystem of the gut is part of the human microbiome, which also exists on the skin. It is thought to be key to regulating the body’s function, the way it digests food, vitamins and medicines and how it repels infection and disease.

Summit chief medical officer Dr David Roblin said: “Ridinilazole is a precision antibiotic that is designed to selectively target C.difficile while being highly preserving of the gut microbiome that plays a crucial role in naturally protecting against recurrent CDI.

Highly selective

“Ridinilazole has now provided evidence of its high selectivity in two complementary clinical trials.

“The data from our earlier phase II trial showed a greater microbiome preservation of ridinilazole-treated patients compared with the current standard of care, vancomycin, which led to achieving statistical superiority in sustained clinical response.”

The latest study is a different one from the phase III trial of ridinilazole currently underway and is expected to yield early data in first half of next year. It gave limited pointers on efficacy compared with fidaxomicin.

An earlier phase II trial, which pitched ridinilazole against vancomycin, delivered impressive results in phase II.

Clinerion, Novartis, RxEOB, And More: News From August 2017

August 31, 2017 | August was full of exciting news in the clinical trial and healthcare community, including partnerships and products from Clinerion, Novartis, RxEOB, and more.



RxEOB has authored the case study, “Utilizing RxEOB MercuryMessaging to promote mammograms.” The RxEOB case study highlights how health care plans wanting to increase the percentage of appropriate patients getting mammograms can do so through better and effective communications using a patient-centric messaging platform. The American College of Radiology and American Cancer Institute both recommend regular mammograms in women beginning at age 40. Unfortunately, for a variety of reasons, the percentage of women who receive an annual mammogram is only 65%. According to the RxEOB case study, “Health plans are interested in improving their mammogram screening rates because it is critical for early detection of breast cancer and for patient health.” It goes on to say, “RxEOB MercuryMessaging maximizes the digital connections and does so with minimal message noise and false positives.” Press release

Clinerion has redesigned the web application for Patient Recruitment System, creating a sleek, professional and intuitive new user interface with analytical capabilities. The system’s functionality and speed have been improved, further supporting decision-making for clinical trial site selection and recruitment strategies. The Patient Recruitment System (PRS) web application has been completely redesigned, using state of the art web design principles based on Material Design. It now incorporates new functionalities and improvements in ease-of-use, resulting in a modern, visually attractive, intuitive and user-friendly appearance. The entire application can now be used on touch displays. Press release

Novartis announced the launch of a mobile research study for people with multiple sclerosis (MS) that collects data via their smartphone, without the need for clinic visits. The study, Evaluation of Evidence from Smart Phone Sensors and Patient-Reported Outcomes in Participants with Multiple Sclerosis (elevateMS), is designed to collect sensor-based data from physical tasks and symptoms. It aims to improve understanding of the daily challenges patients with MS can have and to uncover new potential measurements of treatment effectiveness through real-time data collection from participants in their everyday life. The elevateMS study, which was developed in partnership with Sage Bionetworks, uses a mobile application that was built on the Apple ResearchKit platform. This emerging digital smartphone research platform allows study participants to contribute to research from home or on the go. At the same time, it enables researchers to collect data in the participant’s everyday environment. Press release

Certara announced that it has added externalization technology to its D360 scientific informatics platform. The resulting new product, D360 Partner, facilitates collaboration between sponsors and their external research partners. Those external collaborators could include academic institutions, contract research organizations or third-party research groups. Those partners all have similar data access and communication requirements to members of an internal research project. “Prior to the launch of D360 Partner, this type of collaboration required a custom solution, posing challenges both from an information technology and an informatics perspective. Our new solution provides external research partners with highly secure access to only authorized project data,” David Munro, president, Phoenix Technologies at Certara, said in a press release. Press release

CHRISTUS Health System announced the initial results of the system-wide transition from manual patient intake to Epion Health’s integrated digital check-in platform, using iPads to check patients into their appointments. The move represents a significant step for CHRISTUS, impacting all of its clinic locations across Texas, Arkansas and Louisiana. The Epion Check-in solution provides bi-directional integration with athenahealth, CHRISTUS Health’s electronic health record (EHR) provider, 100% data security and a robust rules engine. EHR integration empowers patients to review and edit existing personal health information already in the system, while adding information to the record appropriate for their scheduled appointment, saving significant time at check-in. Press release

Mauna Kea Technologies announced the peer-reviewed publication of a clinical study demonstrating improved early stomach cancer detection with Cellvizio2 in Endoscopy, the official journal of the European Society of Gastrointestinal Endoscopy (ESGE) and affiliated societies. The new data builds on a recently published meta-analysis3 of Cellvizio in stomach cancer and further establishes the superiority of biopsies guides by a combination of endoscopic imaging with Flexible spectral Imaging Colour Enhancement (FICE) and probe-based confocal laser endomicroscopy (pCLE) with Cellvizio, compared to standard FICE without pCLE for in vivo detection of pre-cancerous and cancerous gastric lesions. Press release

Medisafe announced the official launch of Medisafe Insights. Eclipsing 4 million users and 1 billion doses managed, Medisafe is turning its database of patient information, combining demographics, medication details, medical conditions and comorbidities, engagement with content and interventions, and other key information, into actionable insights for pharma. Medisafe Insights is a proprietary tool for market research (HIPAA compliant and ISO secure), which provides the pharmaceutical industry real-time information regarding patient behavioral trends impacting medication management. With a suite including a de-identified dashboard of high level trends, a targeted and context-aware survey tool and custom enterprise solutions, Medisafe Insights reveals obstacles throughout the patient journey and enables pharma to turn patient behaviors into aggregated actionable insights.  The launch of Medisafe Insights comes one year after announcing its commercial offering for pharma and life sciences companies and launching several successful pilot programs. Press release

SERMO announced a new feature for its pioneering Drug Ratings platform. In addition to allowing physicians to rate and review prescription drugs according to their own clinical experiences, SERMO Drug Ratings now enables physicians to search for and research prescription drugs by FDA-approved indications. “Drugs don’t walk into the doctor’s office – patients with conditions do. Doctors tend to think of the patient’s condition first and then think of the available treatment options. Now that physicians can search the Drug Ratings database by indication, they can discover the highest ranked treatment approaches for each indication as well as evaluate how peers rate all approved drugs against each other,” said SERMO CEO Peter Kirk, in a press release. “Drug ratings for doctors, by doctors are an entirely new resource in medicine, enabling doctors to discover new and physician-preferred treatment options for patients in real time.” With the new feature physicians can evaluate different classes of drugs against each other for treating specific conditions, or compare unique brands. They can examine the drug’s overall rating, as well as see how other physicians rank classes and drugs on efficacy, safety, tolerability, accessibility, and adherence. This enables doctors to find information as quickly or in as much detail as they need. Press release

Natural Language Processing (NLP) text analytics provider Linguamatics, and RealHealthData announced their strategic partnership to combine Linguamatics’ advanced NLP technology with RealHealthData’s extensive database of detailed provider narratives, to improve the understanding of drug use, adverse events, and product switching in Real World settings. Understanding the real world (i.e., outside of clinical trials) impact of therapies on patients is critical for pharmaceutical and biotech companies. Medical records are one of the key sources of real world data, and provide evidence that can inform all phases of drug development. RealHealthData provides access to patient narratives from all 50 US states and every medical specialty. The data can be used for all phases of drug development and post marketing research. Linguamatics I2E can be used to extract the key facts from these narratives using relevant ontologies and queries, transforming real world data into actionable intelligence for better decision making. Press release

Firma Clinical Research is pleased to announce its contribution to the FDA approval of Melinta Therapeutics’ lead antibiotic, Baxdela (delafloxacin), for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible bacteria. Firma was selected by Melinta to provide clinical pharmacology consulting, medical writing, and statistical services for the clinical trials and regulatory submission of their drug Baxdela. “We’re thrilled to support the Melinta team in this FDA approval, and gratified this product will be available for patients suffering with ABSSSI,” noted Christina Fleming, Chief Scientific Officer and President, Clinical Research Services for Firma, in a press release. “Applying our specialized services to provide direct client value is what our team members strive to accomplish.” Press release

Clinipace Worldwide has launched a new regulatory and strategic development consultancy called RSD Global Consulting (RSDGC). With more than 50 specialists, Clinipace RSD Global Consulting provides strategic consulting and regulatory support in the United States, Europe, and Asia Pacific. RSDGC offers stage-specific solutions for all phases of development, from non-clinical and clinical, through to marketing applications and post-marketing support. The group also provides all aspects of pharmaceutical development support, including chemistry, manufacturing, and controls (CMC) strategy; dossier preparation ; pre-approval inspection (PAI) preparation; GxP auditing for compliance in pre-clinical (GLP), clinical (GCP), manufacturing (GMP), medical/regulatory writing, strategic biostatistics and a quality assurance (QA) consultancy.

Novartis and FDA hail ‘historic’ Kymriah, first ever approved CAR-T

In the end, the FDA took little more than six weeks to give final approval to Kymriah, the first ever CAR-T treatment.




The US regulators’ advisors recommended the drug last month, and now the agency has itself backed the drug for use in patients, an historic advance in treating patients with acute lymphoblastic leukemia (ALL), which is set to be the first of many haematological cancers to be targeted.

Kymriah (tisagenlecleucel, known as CTL019 until now) is the first chimeric antigen receptor T cell (CAR-T) therapy, and will now be available for patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.

The novel immunocellular therapy is an historic first because it is the first gene transfer treatment approved by the FDA, and uses a patient’s own T cells to fight cancer.

The Swiss pharma giant has beaten its closest rival, Kite Pharma, to the market,  though its CAR-T treatment is not far behind, looking set for approval in November.

Novartis has already declared that a one-time treatment of the drug will cost $475,000 –  within the range predicted by analysts, but much lower than the $1 million forecasts made initially.

This price reflects that for some patients, the treatment will be seen only as a bridge to transplantation, and therefore only a part of the overall treatment cost.

A big step forward in blood cancers

The promise of the CAR-Ts is enormous for patients with relapsed or refractory ALL, who otherwise face a death sentence after all other therapies have failed.

A pivotal clinical trial of Kymriah in 63 paediatric and young adult patients with the condition found overall remission – a complete absence of the disease –  in 83% of patients within three months of treatment.

If this response proves durable, at least for some patients, it could represent a cure.

Novartis has triumphed in being the first company to bring a CAR-T to market, thanks to its work with immunologist Carl June, one of the earliest pioneers of the technology at the University of Pennsylvania Perelman School of Medicine.

“At Novartis, we have a long history of being at the forefront of transformative cancer treatment,” said Joseph Jimenez, CEO of Novartis. “Five years ago, we began collaborating with the University of Pennsylvania and invested in further developing and bringing what we believed would be a paradigm-changing immunocellular therapy to cancer patients in dire need. With the approval of Kymriah, we are once again delivering on our commitment to change the course of cancer care.”

“This therapy is a significant step forward in individualised cancer treatment that may have a tremendous impact on patients’ lives,” said Carl June, MD, the Richard W. Vague Professor of Immunotherapy, Director of the Center for Cellular Immunotherapies in Penn’s Perelman School of Medicine.

“Through our collaboration with Novartis, we are creating the next wave of immunocellular cancer treatments, and are eager to progress CAR-T therapy in a host of haematologic and other cancer types.”

The FDA Commissioner, Scott Gottlieb, also took the rare step of commenting on a new approval himself.

“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” said Gottlieb.

“New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses. At the FDA, we’re committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving.”

Safety measures

Like other CAR-T treatments in development, Kymriah does carry significant safety risks. The greatest of these is cytokine release syndrome (CRS), an immune system firestorm which has proven fatal in some CAR-T trials.

In the study, 49% of patients treated with Kymriah experienced grade 3 or 4 CRS, however there were no incidents of the cerebral oedema seen in trials of other CAR-T candidates from Kite Pharma and Juno.

The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS), to inform patients and doctors about the risks and monitor safety.

The arrival of CAR-Ts and other gene and cell therapies will also mean that specialist treatment centres will have to be established to administer the drugs. Novartis is also establishing a network of certified treatment centres throughout the country which will be fully trained on the use of Kymriah and appropriate patient care.

Gilead in the picture

The timing of the approval is remarkable, coming just two days after Gilead announced it is buying Novartis’ close CAR-T rival, Kite Pharma for $12 billion.

Analysts will watch closely for how Gilead/Kite will price its rival Axi-cel once it gains approval. Currently under priority review by the FDA, its decision date is 29 November, but a ruling could come earlier as it has with Novartis.

Novartis says it intends to launch a variety of US patient access programmes to support access for patients, including the standard measures to help patients navigate insurance coverage and providing financial assistance for the uninsured or underinsured.

The company plans additional filings for Kymriah in the US and EU later this year, including applications with the FDA and EMA, for the treatment of adult patients with r/r diffuse large B-cell lymphoma (DLBCL). Additional filings beyond the US and EU are anticipated in 2018.

Outcomes-based approach

Novartis has also announced a novel collaboration with the United States Centers for Medicare and Medicaid Services (CMS) centred around  indication-based pricing and outcomes-based payment.

The indication-based pricing could be particularly important for uptake of Kymriah as it expands its licensed indications; its effects may be much less compelling in other diseases, necessitating a lower price for these patients.

Commenting on its plans for extending its outcomes-based pricing to its new first-in-class treatment, Joe Jimenez said:

“Novartis has been at the forefront of outcomes-based pricing and is very pleased to work with CMS on this first-of-its-kind collaboration with a technology that has the potential to transform cancer care. We look forward to continuing to work with CMS to potentially expand this approach to other products and disease states.”

Subtle Shifts In Trial Startup Challenges

Each year Insight Pharma Reports, a sister publishing arm to Clinical Informatics News, conducts a survey of 100, qualified respondents seeking insight into the trends in clinical trial patient enrollment and recruitment. The third annual survey, which will be released soon, reveals subtle shifts in clinical trials startup challenges.



Our pool of qualified responses comes from sponsors, CROs, PROs (Patient Recruitment Organization), vendors, and site. Sites, CROs, and sponsors represent the majority of the responses. One hundred percent of the respondents currently work in patient recruitment and enrollment.

Responses suggest remaining challenges with enrollment planning and perhaps a slight shift toward modeling and simulation to predict enrollment. Still only half of respondents report using social media to recruit patients, but users are pleased with the performance. On the site side, though, personal relationships and history still seem to outweigh other indicators.

Finding the Right Patients and Keeping Them

Enrollment planning is challenging. We gave respondents eight options for their biggest challenges and year after year all the options are flagged. Hitting enrollment goals and recruiting deadlines topped the list in both this year’s survey and last year’s. More than 35% of respondents also cited unrealistic protocols, short or unrealistic time frames, and unrealistic budget.

Concern about short enrollment timelines fell a bit in 2017. In 2016, it was the second most frequently mentioned concern, listed by 45% of respondents. In 2017, short enrollment timelines fell to the fourth highest concern at 39%.

Unfortunately, predicting enrollment remains elusive. Investigators and key opinion leaders lost some prestige in terms of enrollment prediction, though both are still heavily used. Respondents using investigator feedback to predict enrollment fell from 64% to 50%; those using key opinion leader recommendations fell from 41% to 31%. Simulation models, meanwhile, gained a bit of traction with 29% of respondents citing their use, a rise of 5 points.

On the whole, most respondents felt their enrollment predictions were accurate. The percentage reporting predictions that were “accurate” or “somewhat accurate” was over 70% both in 2016 and 2017. But, worryingly, the percentage calling predictions “inaccurate” nearly doubled, from 9% to 17%.

Going Social

The number of companies using social media to recruit patients for clinical trials was perfectly split: 50 respondents were using it; 50 were not. Of the half that were using social media for patient recruitment, a vast majority—88%—said it was effective. These responses mirror those from 2016.

Facebook was by far the most popular social media site used for patient recruitment, with 86% of companies using it. Health and wellness blogs came in second. CraigsList and Twitter were closely ranked as the third and fourth most-used platforms. No platform that we asked about—including Pinterest, YouTube, and Instagram—was not used by at least a few companies, and several were using avenues we’d not considered.

When asked to rank the top three most-effective recruiting avenues, social media came in first followed by online advertisements, posters at hospitals and clinics, and connections with advocacy groups. Again, of the 14 survey options that were offered for recruiting efforts, each one was named by at least four respondents, demonstrating the breadth of ongoing recruiting efforts and how varying opinions can be on their usefulness.

Closing the Deal

Unfortunately, sites continue to fall occasionally short of enrollment targets. Most respondents said it only happens 6-15% of the time, but more than 20% of respondents put their answers on the far edges of the range: reporting that they fail to meet enrollment targets either less than 5% of the time or up to 25% of the time.

Patient dropout rates continue to be low. The vast majority of responses—86—report losing less than 15% of patients enrolled in trials, and most of those—49—report losing less than 5% of trial patients, an improvement over last year’s 44.

Relationships With Sites

Existing site and investigator relationships still dictate much of site selection. In fact, the percentage of respondents reporting using third party resources for site selection fell from 25% to 14%. Sponsors and CROs continue to look to historical performance, specific clinical research focus, site experience in the indication, and a site’s ability to target patient population in determining which sites to work with again. These top four indicators of productive sites are unchanged from last year.

Interestingly, only 33% of respondents answered that they choose sites with the help of an internal database of site metrics. But all respondents did answer list their criteria for productive sites. Sites are considered productive when they have a successful historical performance, a specific clinical research focus, a proven ability to target a patient population, and experience in the indication. These four criteria described the most productive sites in both 2016 and 2017.

Report lays out new strategy for UK life sciences

Industry-led plans to breathe new life into the UK’s £64-billion life sciences sector have been unveiled alongside details of £160 million in government funding to fuel progress in the field.


The Life Sciences Industrial Strategy report, penned by immunologist and geneticist Sir John Bell, outlines the findings of an independent sector-led review on how the government can work with industry to help the UK “become an international benchmark for success”.

The recommendations will now be “considered carefully” by the government and used to work towards a sector deal between government and the global life sciences sector, it said.

“We have created a strategy which capitalises on our strong science base to further build the industry into a globally-unique and internationally competitive life sciences eco-system, supported by collaboration across industry, government, the NHS, academia, and research funders to deliver health and wealth,” said Sir John.

The strategy is organised under five key themes – science, growth, NHS, data, and skills – with proposals to build on the UK’s strengths in each area.

Recommendations include reinforcing the UK science offering with a funding boost for basic science and also by improving the country’s clinical trial capabilities, and ensuring the country has the talent and skills to underpin future life sciences success through a reinforced skills action plan across the NHS, commercial and third sectors.

Elsewhere, it calls for a tax environment that will support growth and attract substantial investment, and the establishment of up to five regional innovation hubs providing health data to help researchers make better use of evidence available.

Encouraging collaboration with the NHS is also a central theme and, as such, the report is recommending that the Accelerated Access Review be adopted with national routes to market streamlined and clarified, including for digital products.

Delving deeper into the detail, the strategy lists measures to further improve access to innovation, including conditional reimbursement for therapies that have shown promise in UK based trials at the point of licensing, a forum to facilitate early engagement between industry, NHS and NICE to agree commercial deals, and expansion of NICE tools beyond the QALY to assess value.

£160 million to support advanced therapies, vaccines
Alongside its publication Health Secretary Jeremy Hunt has unveiled £14 million in funding to support 11 medical technology research centres to further encourage collaboration between the NHS and industry in developing and bringing new technologies to patients through the National Institute for Health Research (NIHR).

In addition, Business Secretary Greg Clark announced the first phase of the government’s new investment in life sciences with funding of £146 million of funding for ‘cutting-edge’ projects, which is also expected to leverage more than £250 million of private funding from industry. The investment will be spread over four years and covers five major projects supporting advanced therapies, advanced medicines and vaccines development and manufacturing.

Mike Thompson, chief executive of the ABPI, welcomed the plans. The Strategy “is an impressive document which captures the importance of our sector to a successful post-Brexit Britain. We want the UK to be one of the best places in the world for discovering, developing and adopting new medicines and this Strategy provides the focus for all life science partners to work together to deliver exciting medical innovations for patients.

“We look forward to working with Government and other partners to implement these recommendations – including through a sector deal with the bio-pharmaceutical industry and a voluntary agreement on UK medicines policy between industry and the Department of Health. These measures will provide confidence for global companies to invest in the UK during and beyond Brexit.”

Also commenting on the strategy, Professor Sir Robert Lechler, president of the Academy of Medical Sciences, said it “recognises the importance of funding across basic and discovery science, and translational research.

“Maintaining and enhancing an environment which supports research across the whole ecosystem including academia, industry, the NHS and charities, is essential to allow the UK’s life sciences sector to continue to flourish,” he stressed, and also emphasised the importance of supporting life sciences clusters, regional strengths and cross-sector collaboration.”

The government will respond formally to the proposals in its life sciences sector deal, expected later in the year.

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