Category Archives: Genetic Medicine

When Anne Weber became pregnant with her first child at age 28, little did she suspect that, rather than bringing home a bundle of joy, she would have to contend with a cancer diagnosis that would change the course of her life.

At her first ultrasound, not only did she find out that she had miscarried but also that she had a large cyst on one of her ovaries. That cyst turned out to be cancer.

"Because I didn't have a strong family history of cancer, everyone assumed it would be benign," she recalled in an interview with Medscape Medical News. "We were all very surprised when the pathology report came back with ovarian cancer."

Although the incidental finding may have been heartbreaking, it may also have been lifesaving. Because it was caught early, her ovarian cancer was of stage I. She underwent surgery and is now telling her story, 10 years later.

Weber is now a patient advocate at FORCE (Facing Our Risk of Cancer Empowered), a national nonprofit organization dedicated to individuals affected by hereditary breast, ovarian, and related cancers, andpreviously worked for a while at genetic testing company Myriad Genetics.

How Weber developed ovarian cancer at such a young age was initially a mystery. Without a family history and without symptoms or personal risk factors for it, her physician did not suspect a hereditary cancer even though at the time, National Comprehensive Cancer Network (NCCN) guidelines recommended that physicians consider genetic testing for anyone younger than 50 who are found to have ovarian cancer. However, her physician didn't offer genetic testing, or even counsel her about it.

Weber was left with nagging questions. She wanted to know why she'd gotten ovarian cancer and how she could prevent a recurrence. So she started sleuthing around on the Internet.

"When I was diagnosed, I knew nothing about this. Literally, I didn't know what terms to type into the search engine," she said.

When she stumbled onto an online forum that linked her to the NCCN guidelines, the pieces of the puzzle began fitting together.

This was 2009, and she was living in Atlanta at the time. She asked her physician about genetic testing, and her doctor referred her to the only genetic counselor in the city, who was at Emory University. At that time, the wait time for genetic testing was 6 months.

"Six months when you're dealing with something like cancer can be pretty dire," Anne said.

Genetic testing for breast and ovarian cancer has not always been straightforward, and fast-moving research means that genetic testing is becoming more and more complex all the time.

The NCCN may have recently provided a step in the right direction. On December 4, the NCCN released updated clinical practice guidelines on genetic/familial high-risk assessment for breast and ovarian cancer.

The guidelines represent a fairly radical shift from previous recommendations, which focused on BRCA genes, according to Robert Pilarski, MS, LGC, MSW, LSW, a genetics counselor and professor of clinical internal medicine at Ohio State University's Comprehensive Cancer Center. He was also vice chair of the NCCN guidelines panel that updated the guidelines.

The NCCN recommendations remain anchored in strong, unbiased evidence and reflect a conservative approach regarding genes for which there is lack of evidence, he said. But the guidelines also acknowledge a shift toward panel testing and include a table of 17 moderate- and high-penetrance genes that should be considered in addition to BRCA genes. They also provide management recommendations for people who carry these genes.

"Most people now are doing panel testing where the panel involves multiple genes besides BRCA," Pilarski said, "This guideline update is the closest that we've got to a consensus [regarding breast, ovarian, and pancreatic cancer] because it now specifies a set of genes that are reasonable to include in at least a basic panel."

The use of multigene panels is controversial, as previously reported by Medscape Medical News. A study published in early 2019 in the Journal of Clinical Oncology suggested that roughly half of breast cancer patients who carry a pathogenic or likely pathogenic mutation are missed by current genetic testing guidelines. That study used an 80-gene panel, and the authors recommended expanded panel testing for all patients with breast cancer.

Critics shot back, arguing that universal testing is not warranted and that large, multigene panels may create undue anxiety among patients as well as confusion among physicians. Research is in its infancy for many of these genes, and physicians don't know how or even whether to act on results for some of them. That's especially true for variants of unknown significance, which have not been confirmed to increase risk for disease.

Perhaps in response to this controversy, the NCCN guidelines do not recommend universal testing for breast or ovarian cancer. Instead, they provide clinical scenarios in which genetic testing is clinically indicated, may be considered, or has low probability of clinical utility. The NCCN authors hedge their bets by not endorsing for or against multigene panel testing.

"I think we held back from becoming too definitive because there may be times when other genes are appropriate," Pilarski explained. "We didn't want to lock patients out of insurance coverage, and we didn't want to lock ourselves into a set of genes that could change next week with changing evidence."

This "wishy-washiness" over multigene panels creates a problem for Mehmet Copur, MD, FACP, an oncologist who wrote a critical response to the study published earlier this year. He is affiliated with the Morrison Cancer Center in Hastings, Nebraska, and is an adjunct professor at the University of Nebraska Medical Center in Omaha.

"I believe they have tried to please both parties, and they have been too nice," he said. "My personal opinion is that I would go for high-penetrance genes in clinically suspicious settings. I would ignore that disclaimer note and say, 'I'm going to do this 17-gene panel.' "

Going one step further, he suggested the creation of commercially available gene panels based on the NCCN recommendations for these 17 genes.

"There are a wide variety of panels available with different genes on different panels. There is a lack of consensus among experts regarding which genes should be tested in different clinical scenarios. If possible, it would be helpful to create commercially available gene panels based on the updated NCCN recommendations," he said.

In another major change, the guidelines now include pancreatic cancer for the first time. But in contrast to breast and ovarian cancer, the NCCN recommends that all patients with newly diagnosed pancreatic cancer receive genetic testing.

"Approximately 1 in 20 patients with pancreatic cancer will have an inherited susceptibility gene. Most people with pancreatic cancer who carry these mutations do not have a family history of pancreatic cancer, so you can't rely on family history to guide you about who should get genetic testing," Michael Goggins, MD, MBBCH, who was also involved in updating the NCCN guidelines, told Medscape Medical News. Goggins is director of the Pancreatic Cancer Early Detection Laboratory at Johns Hopkins University School of Medicine, Baltimore, Maryland.

Advantages of genetic testing for pancreatic cancer include guidance regarding choice of chemotherapy and the possibility of cascade testing for prevention or earlier detection of pancreatic cancer in family members.

Other additions to the guidelines include new recommendations for genetic testing for individuals with Ashkenazi Jewish ancestry, as well as new or updated recommendations for Li-Fraumeni syndrome and Cowden/PTEN hamartoma tumor syndrome.

The guidelines also offer an expanded section on genetics risk assessment and genetic counseling. Genetic testing has become increasingly complex, and the NCCN emphasizes the importance of genetic counseling throughout the testing process.

It has been 10 years since Anne Weber was diagnosed with ovarian cancer. Because she was diagnosed at a young age (28 years) and her other ovary was unaffected, she opted for surgery to remove only the ovary with the tumor.

After her own Internet research and at her own request, Weber underwent genetic testing. She found out that she is a carrier of the BRCA2 mutation, which carries high risk for breast, ovarian, and pancreatic cancer.

Current recommendations are that people with BRCA2 mutations start breast cancer screening at age 25, so Weber was screened immediately.

Her first breast MRI revealed a mass that was found to be stage I breast cancer. At that point, she chose to have her other ovary removed, as well as both fallopian tubes and both breasts, which significantly reduces her risk for recurrence.

"I'm so incredibly grateful that I found the information. All the guidelines say that I shouldn't even have had my first mammogram at my current age of 39. So there is low likelihood that I would have been diagnosed by now, and it certainly would not have been stage I," she said.

Since her diagnosis, she and her husband have adopted a child.

"Genetic testing isn't right for everyone. People aren't going to make the same decisions I did," she said. "The biggest thing is to understand that being positive doesn't mean that you're going to get cancer. It just allows you to have that circle of care to try to prevent cancer, or at least catch it earlier, when it's more treatable."

NCCN. Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic Version 1.2020. Full text

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Heartbreaking News, Then Tumor Find Leads to Genetic Testing - Medscape

Often, science moves ahead incrementally. Yet sometimes it advances in dramatic leaps and bounds that can stir new hopes for medical benefits while shaking society to its very core. We saw both in 2019, as work using the gene-editing tool CRISPR gained momentum.

The year opened with the scientific community scrambling to respond to the news that Chinese researcher He Jiankui had used CRISPR technology to edit the genomes of human embryos. The experiments resulted in the November 2018 birth of twin girls, the first humans with genetically altered germline cells which means their genetic changes are heritable and can be passed on to future generations.

The National Institutes of Health (NIH), a crucial public supporter of biomedical research, is among the many who consider such experiments both irresponsible and unethical. The NIH has not funded any use of heritable gene-editing technologies in human embryos, and it has no intention of doing so.

But NIHs strong stance against heritable gene editing does not mean that we think CRISPR has no role in the future of clinical medicine. This innovative technology possesses enormous potential for therapeutic good if used for making nonheritable genetic changes. In that approach, genetic material is altered only in relevant somatic (nonreproductive) cells, so there is no chance of passing those changes on to future offspring.

NIHs highest priorities in 2019 included supporting research aimed at using nonheritable gene editing to help people with life-threatening disorders, such as sickle cell disease, HIV infection, cancer and muscular dystrophy. Indeed, such applications may offer the best hope not only for treating, but for curing, many of the nearly 6,000 human genetic diseases that still lack treatments.

Now, scientists and leaders around the globe have an obligation to consider the appropriate use if any of heritable human gene editing. This involves scrutinizing the safety of such experiments, including the risk of unintended mutations, as well as a clear-eyed analysis of actual medical need. In our view, the current arguments that the benefits outweigh the risks are surprisingly uncompelling. But our deliberations should not stop there. We must weigh the profound social, ethical and moral issues associated with modifying the germline in ways that could change the human species forever.

Given the significance of these decisions, in March, leading scientists from seven countries led by Eric Lander and including CRISPR pioneers Feng Zhang and Emmanuelle Charpentier called for a five-year international moratorium on the use of gene editing to modify the human germline for clinical purposes. The NIH supports such a moratorium.

Despite the calls for caution, some researchers are forging ahead. In June, Russian molecular biologist Denis Rebrikov announced plans to implant gene-edited embryos into women. Like his Chinese counterpart, Rebrikov planned to use CRISPR to target the CCR5 gene to protect against HIV; he later changed course to focus on GJB2, a gene linked to heritable hearing loss.

Direct editing of embryos is not the only way to alter the human germline in heritable ways: In August, New York-based reproductive biologist Gianpiero Palermo went public with his plans to use CRISPR technology to target a gene that increases cancer risk in human sperm.

But such moves continued to meet vigorous opposition. In August, a number of research groups working on gene-editing therapeutics issued a statement asserting heritable gene editing is currently inappropriate for use in human clinical studies. That same month, a group of international research societies convened to discuss recommendations for appropriate research, which are slated for completion in spring of 2020.

Meanwhile, the World Health Organizations new expert advisory committee, convened in the wake of Hes experiments, sidestepped the issue of a moratorium at its August meeting. It did, however, establish a global registry to track all kinds of human gene-editing research and to offer consultation on governance of such technologies.

A moratorium of at least five years on heritable human gene editing would provide us time to engage in proactive, rather than reactive, discussions about the future of such technology. That discussion has to be inclusive of many societal perspectives. We must never allow our technology to eclipse our humanity. As an interconnected global society, we have a responsibility to ask ourselves some very hard questions about heritable gene editing and the dangers of human hubris. While difficult, this is a debate that we simply cannot afford to postpone.

Francis S. Collins is the director of the National Institutes of Health.

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NIH Director on Human Gene Editing: 'We Must Never Allow our Technology to Eclipse our Humanity' - Discover Magazine

Media Advisory

Friday, December 27, 2019

Findings from NIH-funded study could inform treatment strategies.

Identical twins with autism spectrum disorder (ASD) often experience large differences in symptom severity even though they share the same DNA, according to an analysis funded by the National Institutes of Health. The findings suggest that identifying the causes of this variability may inform the treatment of ASD-related symptoms. The study was conducted by John Constantino, M.D., of Washington University School of Medicine in St. Louis, and colleagues. Funding was provided by NIHs Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study appears in Behavior Genetics.

ASD is a developmental disorder that affects how a person behaves, interacts with others and learns. Previous studies have found that when one identical twin has ASD, chances are extremely likely that the other twin has it, too.

The authors analyzed data from three previous studies comprising a total of 366 identical twin pairs with and without ASD. The severity of autism traits and symptoms in the twins was measured by a clinicians assessment or by parents ratings on a standardized questionnaire. Some cases were diagnosed by both methods. The researchers determined a 96% chance that if one twin has ASD, the other has it, too. However, symptom scores varied greatly between twins diagnosed with ASD. The researchers estimated that genetic factors contributed to only 9% of the cause of trait variation among these twins. In contrast, among pairs of identical twins without ASD, the scores for traits were very similar.

The study authors do not know the reasons for differences in symptom severity, but they rule out genetic and most environmental causes because the twins share the same DNA and were raised in the same environment. Additional studies are needed to determine the cause.

Alice Kau, Ph.D., NICHD Intellectual and Developmental Disabilities Branch, is available for comment.

Castelbaum, L. On the nature of monozygotic twin concordance for autistic trait severity: A quantitative analysis. Behavior Genetics.2019.

About theEunice Kennedy ShriverNational Institute of Child Health and Human Development (NICHD): NICHD conducts and supports research in the United States andthroughout the world on fetal, infant and child development; maternal, child and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visitNICHDs website.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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Severity of autism symptoms varies greatly among identical twins - National Institutes of Health

Filmmaker and actor Xavier Dolan and the co-founders of the Montreal International Jazz Festival, Andr Mnard and Alain Simard, were among those who were inducted into the Order of Canada on Friday. Legendary Quebec actor Marcel Sabourin, 84, was named an Officer of the Order.

Artists, former politicians, scientists and community leaders were recognized for their extraordinary contributions. A total of 120 people were either appointed to the Order or received promotions.

Former prime minister Stephen Harper and former ambassador Raymond Chrtien received the highest rank of Companion to the Order.

Mnard and Simard were appointed Officers Mnard for his contribution to the Montreal cultural scene, notably as artistic director of the (jazz festival), Simard for his key role in positioning Montreal as a city of festivals and for his leadership as the head of quipe Spectra.

Among the other new Officers of the Order are four-time Olympic womens hockey gold medallist Caroline Ouellette and former Quebec cabinet minister Raymond Bachand.

Denyse McCann, a co-founder of quipe Spectra, was selected as a Member of the Order. Dolan received the same honour for his talent, which has earned him international recognition as an actor, screenwriter and director. Gilles Ste-Croix was also appointed as a Member for his creativity and imagination as co-founder and director of the Cirque du Soleil.

In the university and scientific sector, UQAM professor Alain-G. Gagnon (Officer) was recognized for his contribution to the social sciences, notably for his research into federalism, francophone-anglophone relations, and national identities.

McGill University Professor Daniel Jutras (Officer), was honoured for his contributions to the development of pluralist law internationally and for his contributions as a lawyer, professor and university administrator.

CHUM researcher Pavel Hamet (Member), was recognized for his contributions to genetic medicine and to the development of new clinical treatments for hypertension and diabetes.

Jean-Charles Coutu, the former mayor of Rouyn-Noranda (Officer), was praised for his contributions to the legal profession in the area of Indigenous justice and for his community involvement.

Elsewhere in Canada, biologist Anne Dagg, known as the queen of giraffes, became a Member of the Order for her contributions to the modern scientific understanding of the giraffe.

Dagg was one of several women honoured by the Order for their scientific work, including 2018 Nobel Prize winner Donna Strickland (Companion) and Noni MacDonald of Halifax (Officer), a pediatrician who has served on behalf of the World Health Organization.

Other Montrealers named to the Order:

Officers

Annette av Paul, for her contributions to ballet and for her mentorship as a dancer, teacher and director.

Karen Messing, for her pioneering research into ergonomic work conditions, particularly as they affect womens health.

Members

Maurice Brisson, for his expertise in designing electrification plans and for his philanthropic contributions to electrical engineering education.

Marie Gigure, for her leadership in commercial and corporate law, for her commitment to increasing the role of women in business, and for her dedication to the community.

Arshavir Gundjian, for his contributions to recognizing and promoting Armenian culture in Canada and abroad.

Alcides Lanza, for his decades-long contributions to the contemporary music scene and for championing Canadian music here and abroad.

Isabelle Marcoux, for promoting diversity within Quebecs economic community and for her involvement in numerous fundraising campaigns.

Robert Dick Richmond, for his innovative designs as an aeronautical engineer and for his contributions to the aviation industry.

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Xavier Dolan, Andr Mnard and Alain Simard appointed to the Order of Canada - Montreal Gazette

Scientists adding human brain genes to monkeys its the kind of thing youd see in a movie like Rise of the Planet of the Apes. But Chinese researchers have done just that, improving the short-term memories of the monkeys in a study published in March in the Chinese journal National Science Review. While some experts downplayed the effects as minor, concerns linger over where the research may lead.

The goal of the work, led by geneticist Bing Su of Kunming Institute of Zoology, was to investigate how a gene linked to brain size, MCPH1, might contribute to the evolution of the organ in humans. All primates have some variation of this gene. However, compared with other primates, our brains are larger, more advanced and slower to develop; the researchers wondered whether differences that evolved in the human version of MCPH1 might explain our more complex brains.

Su and his team injected 11 rhesus macaque embryos with a virus carrying the human version of MCPH1. The brains of the transgenic monkeys those with the human gene developed at a slower pace, akin to that of a human, than those in transgene-free monkeys. And by the time they were 2 to 3 years old, the transgenic monkeys performed better and answered faster on short-term memory tests involving matching colors and shapes. However, there werent any differences in brain size or any other behaviors.

But the results arent what has the scientific community buzzing. Some individuals question the ethics of inserting a human brain gene into a monkey an action Rebecca Walker, a bioethicist at the University of North Carolina, argues could be the start of a slippery slope toward imbuing animals with humanlike intelligence. In a 2010 paper, James Sikela, a geneticist at the University of Colorado School of Medicine, and coauthors asked whether a humanized monkey would fit into its society, or would live in inhumane conditions due to its altered genes.

To justify the work, Su and his co- authors suggested that it could provide insights into neurodegenerative and social disorders but they dont describe what those applications might be. I dont really see anything in the paper that would make me think that [the experiment] was necessarily a good idea, says Walker.

Su declined Discovers request for comment, but said in an article for China Daily, Scientists agree that monkey models are at times irreplaceable for basic research, especially in studying human physiology, cognition and disease. And in the research paper, the authors contend that the relatively large phylogenetic distance (about 25 million years of divergence from humans) alleviates ethical concerns. (Rhesus macaques are less like humans in terms of social and cognitive capacities than primates such as chimpanzees, which are more closely related to us.) This greater evolutionary distance suggests it would be harder to wind up with a macaque that acts like a human.

But that reasoning falls flat for Walker. It doesnt really matter when they became differentiated from humans on the phylogenetic tree, she says. Theyre talking about improved short-term memory, which would be putting them sort of closer to us in terms of those cognitive abilities. She thinks manipulating these skills makes the work ethically dubious and requires stronger justification.

While monkeys and humans have similar genomes, Su said in the China Daily article, there are still tens of millions of genetic differences. Changing one gene carefully designed for research will not result in drastic change.

Sikela agrees that such a change may be minor. Still, he wonders about the possibility of finding a gene with a large effect on cognition.

Theres some risky elements to going down this road, Sikela says. One needs to think about the consequences of where this is leading and whats the best way to study these kinds of questions.

Walker also worries about where this work leads. Could we enhance human brains through these methods? she asks. While she thinks were nowhere close to that yet, she notes that science can advance surprisingly quickly. For instance, CRISPR the gene-editing technique that once seemed far removed from human research was used in China to edit the genomes of twins in 2018. (See our No. 11 story of the year, page 32.)

It does feel worrisome to be doing this research in primates, Walker says. And then potentially thinking about how that could be used in humans.

[This story originally appeared in print as "Researchers React to Human Genes in Monkeys."]

Read more here:
Scientists Put a Human Intelligence Gene Into a Monkey. Other Scientists are Concerned. - Discover Magazine

Image Credit: AFP

For all the flak the pharmaceutical industry has taken for its exorbitant pricing practices, theres no getting around the fact that its been a pretty stunning decade for medical progress.

Multiple new categories of medicines have moved from dreams and lab benches into the market and peoples lives, and investors who came along for the ride often reaped extraordinary profits. The Nasdaq Biotech Index is up 360 per cent over the last 10 years to the S&P 500s 190 per cent. And thats without mentioning the hundreds of billions of dollars in takeovers that rewarded shareholders with windfalls.

As 2020 approaches, its worth highlighting how far weve come in the past 10 years in developing new therapies and approaches to treating disease, even as politicians grapple with how to rein in health-care costs without breaking an ecosystem that incentivises the search for new discoveries.

Here are some of the decades biggest medical breakthroughs:

Cell therapies

First approved in the US two years ago, these treatments still sound like science fiction. Drugmakers harvest immune cells from patients, engineer them to hunt tumours, grow them by the millions into a living drug, and reinfuse them. Yescarta from Gilead Siences Inc. and Novartis AGs Kymriah the two treatments approved so far can put patients with deadly blood cancers into remission in some cases. At the beginning of the decade, academics were just beginning early patient tests.

Its still early days for the technology, and some issues are holding these drugs back. There are significant side effects, and the bespoke manufacturing process is expensive and time-consuming. That has contributed to a bruising price tag: Both of the approved medicines cost over $350,000 (Dh1.28 million) for a single treatment. And for now, cell therapy is mostly limited to very sick patients who have exhausted all other alternatives.

Luckily, more options are on their way. Some drugmakers are focused on different types of blood cancers. Others hope to mitigate side effects or create treatments that can be grown from donor cells to reduce expenses and speed up treatment. In the longer run, companies are targeting trickier solid tumours. Scientists wouldnt be looking so far into the future without this decades extraordinary progress.

Gene therapies

Researchers have spent years trying to figure out how to replace faulty DNA to cure genetic diseases, potentially with as little as one treatment. Scientific slip-ups and safety issues derailed a wave of initial excitement about these therapies starting in the 1990s; the first two such treatments to be approved in Europe turned out to be commercial flops.

This decade, the technology has come of age. Luxturna, a treatment developed by Spark Therapeutics Inc. for a rare eye disease, became the first gene therapy to get US approval in late 2017. Then in May came the approval of Novartis AGs Zolgensma for a deadly muscle-wasting disease. The drugs have the potential to stave off blindness and death or significant disability with a single dose, and, unsurprisingly, Big Pharma has given them a substantial financial endorsement. Roche Holding AG paid $4.7 billion to acquire Spark this year, while Novartis spent $8.7 billion in 2018 to buy Zolgensma developer Avexis Inc.

Dozens of additional therapies are in development for a variety of other conditions and should hit the market in the next few years. They offer the tantalising potential not just to cure diseases, but to replace years of wildly expensive alternative treatment. If drugmakers can resist the temptation to squeeze out every ounce of value by doing things like charging $2.1 million for Zolgensma, theres potential for these treatments to save both lives and money.

RNA revolution

The above treatments modify DNA; this group uses the bodys messaging system to turn a patients cells into a drug factory or interrupt a harmful process. Two scientists won a Nobel Prize in 2006 for discoveries related to RNA interference (RNAi), one approach to making this type of drug, showing its potential to treat difficult diseases. That prompted an enormous amount of hype and investment, but a series of clinical failures and safety issues led large drugmakers to give up on the approach. Sticking with it into this decade paid off.

Alnylam Inc. has been working since 2002 to figure out the thorny problems plaguing this class of treatments. It brought two RNAi drugs for rare diseases to the market in the past two years and has more on the way. The technology is also moving from small markets to larger ones: Novartis just paid $9.7 billion to acquire Medicines Co. for its Alnylam-developed drug that can substantially lower cholesterol with two annual treatments.

Ionis Pharmaceuticals Inc. and Biogen Inc. collaborated on Spinraza, a so-called antisense drug that became the first effective treatment for a deadly rare disease. It was approved in late 2016 and had one of the most impressive drug launches of the decade. And Moderna Therapeutics rode a wave of promising messenger RNA-based medicines to the most lucrative biotechnology IPO of all time in 2018. From pharma abandonment to multiple approvals and blockbuster sales potential in under 10 years. Not bad!

Cancer immunotherapy

Scientists had been working on ways to unleash the human immune system on cancers well before the 2010s without much luck. Checkpoint inhibitors drugs that release the brakes on the bodys defence mechanisms have since produced outstanding results in a variety of cancers and are the decades most lucrative turnaround story.

Merck got a hold of Keytruda via its 2009 acquisition of Schering-Plough, but it was far from the focus of that deal. Once Bristol-Myers Squibb & Co. produced promising results for its similar drug, Opdivo, Merck started a smart development plan that has turned Keytruda into the worlds most valuable cancer medicine. Its now available to treat more than 10 types of the disease, and has five direct competitors in the US alone. Analysts expect the category to exceed $25 billion in sales next year.

If anything, the drugs may have been too successful. Copycat efforts are pulling money that could fund more innovative research. There are thousands of trials underway attempting to extend the reach of these medicines by combining them with other drugs. Some are based more on wishful thinking than firm scientific footing. Still, the ability to shrink some previously intractable tumours is a considerable advance. If drugmakers finally figure out the right combinations and competition creates pricing pressure that boosts access, these medicines will do even more in the years to come.

Conquering hepatitis C

From a combined economic and public-health standpoint, a new group of highly effective hepatitis C medicines may outstrip just about anything else on this list so far. Cure rates for earlier treatments werent especially high; they took some time to work and had nasty side effects. The approval of Gileads Sovaldi in 2013, followed in time by successor drugs such as AbbVie Inc.s Mavyret, have made hepatitis C pretty easily curable in a matter of weeks. For Gilead, getting to market rapidly with its drug proved enormously profitable; it raked in over $40 billion in revenue in just three years.

Hepatitis C causes liver damage over time that can lead to transplants or cancer. The existence of a rapid cure is a significant long-term boon even if the initial pricing on the drugs made them, in some cases, prohibitively expensive. Sovaldi notoriously cost $1,000 per pill at launch and over $80,000 for a course of treatment. The good new is, treatments have become a lot more affordable, which should allow this class of drugs to have a broad and lasting positive health impact.

Hepatitis C is one of the relatively few markets where the drug-pricing system has worked well. As competing medicines hit the market, the effective cost of these treatments plummeted. That, in turn, made the drugs more accessible to state Medicaid programmes and prison systems, which operate on tight budgets and care for populations with higher rates of hepatitis C infection. Louisiana has pioneered the use of a Netflix model, under which the state paid an upfront fee for unlimited access to the drug. Its an arrangement that will help cure thousands of patients, and other states are likely to follow its lead.

Many of the medicines highlighted in this column have list prices in the six figures, a trend thats helped drive up Americas drug spending by more than $100 billion since 2009. Building on this decades medical advances is going to lead to even more effective medicines that will likely come with steeper prices. Id like to hope that policymakers will come up with a solution that better balances the need to reward innovation with the need to keep medicines accessible. That would really be a breakthrough.

Max Nisen is a Bloomberg Opinion columnist covering biotech, pharma and health care.

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The medical breakthroughs of the past decade | Op-eds - Gulf News