THE KENDALL SQUARE biotech boom started nearly a half century ago, with a small number of scientists who had big ideas. In the decades since, the sector has grown dramatically, now employing more than 106,000 people across the state. These range from startups — think a couple of postdocs at an incubator such as Cambridge’s LabCentral — to multibillion-dollar giants such as Moderna and Vertex Pharmaceuticals. Meanwhile, the vibrant sector here — perhaps rivaled globally only by San Francisco’s — has attracted branches of giants from overseas, such as Takeda Pharmaceutical and Eisai of Japan and Novartis of Switzerland.
Whatever the company, whatever the approach, the goals are largely the same: to make life better and healthier through science. Here, we examine 12 diseases and conditions — ranging from cancer to chronic pain, Alzheimer’s to postpartum depression — and the innovative companies working on solutions. Some of those treatments may be years away, or never end up making it over the hurdles of testing and approval at all. Some could be available in a matter of months.
Vertex Pharmaceuticals is Massachusetts’ most valuable biotech company, with a market capitalization of $75 billion. It achieved that success largely by selling four lifesaving (and expensive) drugs for cystic fibrosis, a rare genetic disease that causes problems with breathing and digestion.
Now Vertex is running multiple late-stage trials on a drug to tame an all-too-common malady: pain.
There’s an enormous demand for new pain relievers. Over-the-counter drugs such as aspirin, acetaminophen, ibuprofen, and naproxen were invented generations ago. They are only moderately effective at treating severe pain and can cause stomach or liver problems. Opioids, meanwhile, date back thousands of years. While often highly effective, they have fueled an epidemic of addiction.
Vertex is testing a potent experimental painkiller that doesn’t rely on opioids and is nonaddictive. In a mid-stage study, the pill, dubbed VX-548, significantly reduced acute pain in people recovering from recent surgeries (such as bunion removals and tummy tucks). It’s now being tested in three late-stage trials on acute pain.
Opioids operate in the brain and spinal cord to block pain but pose a high risk for drug abuse, a phenomenon of the central nervous system. In contrast, Vertex’s drug inhibits pain signals in peripheral sensory nerves outside the brain and spinal cord, without the potential for abuse, according to the company.
Vertex aims to have the results of the studies by early 2024. Dr. Brian Abrahams, a physician and biotech analyst with RBC Capital Markets, told investors in a recent note that the drug “could represent a major breakthrough.” – J.S.
The same genetic technology behind the most widely used COVID-19 vaccines may one day help your own body fight cancer with a personalized vaccine.
Americans have now collectively rolled up their sleeves more than 650 million times for a shot of the Moderna or Pfizer COVID vaccine. Both jabs are made with messenger RNA technology that uses synthetic strings of genetic code to coax our bodies into making fragments of the coronavirus, giving our immune systems target practice so they’re prepared to fight back when the real baddie shows up.
Moderna and its competitors have long dreamed of using mRNA vaccines to turn our immune systems inward to fight cancer. Just a couple of months ago, the Cambridge company and its pharma partner Merck provided the first glimmer of evidence that the idea might actually work.
The vaccines are custom-made for each patient to match tidbits of genetic code found in that person’s particular cancer. Moderna’s initial focus was on people whose skin cancer had spread or metastasized. In a medium-size clinical trial, melanoma patients who got the bespoke vaccine, combined with Merck’s cancer immunotherapy drug Keytruda, saw their relative risk of cancer recurrence or death drop by 44 percent over an average of two years. Last year, about 100,000 cases of melanoma were diagnosed in the United States, and about 8,000 people died from it.
Moderna still needs to conduct a larger study to confirm the vaccine’s benefits before asking regulators for approval. But the preliminary trial has already galvanized the company’s plans to make mRNA vaccines for other kinds of cancer.
“It’s a very promising technology for vaccines,” says Dr. Patrick Ott, clinical director of the Melanoma Disease Center at Dana-Farber Cancer Institute, who was involved in the trial. “There’s no reason to think that this may not work in other cancers as well.” – R.C.
3. POSTPARTUM DEPRESSION
Antidepressants such as Prozac and Zoloft are among the most widely prescribed medicines, and many people with depression consider them a godsend. But the drugs come with a big catch: They can take four to six weeks to work.
“If you’re struggling with bad depression, to tell someone it’s going to take a month before you feel better, that seems like a lifetime,” says Dr. Greg Mattingly, a psychiatrist and associate clinical professor at Washington University in St. Louis.
Two Cambridge companies, Sage Therapeutics and Biogen, want to change that with their fast-acting antidepressant, zuranolone. In several clinical trials that Mattingly participated in as a researcher, patients took one pill a day for only 14 days. Some patients reported feeling better in as little as three days.
Not all industry analysts are convinced, however, that zuranolone is a significant improvement over other antidepressants.
Sage sold half the commercial rights for zuranolone, which uses a new scientific approach to treat depression, to Biogen in 2020 as part of a $1.5 billion deal. The partners have asked US drug regulators to approve it as the first antidepressant specifically for postpartum depression and as a new treatment for major depressive order. The FDA is scheduled to make a decision by early August. – J.S.
4. GUT INFECTIONS
Two Cambridge companies are proving that medical marvels can come from the most unlikely of sources. Seres Therapeutics and Vedanta Biosciences are harnessing the healing power of poop to create therapies that use good bacteria found in our feces to fight bad bugs that can cause recurrent infections in the gut.
As bizarre as that idea sounds, it’s based on a surprisingly effective medical procedure where a healthy person’s stool is transferred to a sick person’s digestive tract via enema or processed into a pill and swallowed.
The approach, known as a fecal microbiota transplant, helps people shake a dangerous gut bug — called C. diff — that can cause diarrhea, stomach pain, and colitis, a severe inflammation of the colon, in as many as 500,000 Americans each year. Both local companies are attempting to lower the ick factor.
Seres has developed pills made from bacterial spores purified from feces. About 88 percent of patients with C. diff who got the pills in a clinical study were free of the bug eight weeks after treatment, compared with 60 percent who got a placebo. The pill could get approval from the FDA by the end of April.
Vedanta wants to take poop out of the equation altogether by growing in its labs specific strains of bacteria that it believes are most important for combatting C. diff. The company is planning to start an advanced clinical study this year.
The approaches are the front-runners of an exploding field of research on the microbiome, the assemblage of microscopic denizens that live in and on our bodies.
“Microbial therapeutics have tremendous untapped potential and I’m very excited for the approval of these products,” says Dr. Stacy Kahn, a gastroenterologist at Boston Children’s Hospital. – R.C.
5. HEART DISEASE
In the future, a one-time infusion of a gene-altering medicine could permanently lower cholesterol and dramatically reduce the risk of having a heart attack or stroke.
That may sound like something straight out of science fiction, but it’s actually the goal of Dr. Sekar Kathiresan, an esteemed former cardiologist from Massachusetts General Hospital who launched the Boston biotech firm Verve Therapeutics in 2019 to make his vision a reality.
Verve is developing a therapy that uses a form of CRISPR gene editing to inactivate a gene called PCSK9 in the liver. In studies with monkeys, the genetic tweak significantly reduced levels of LDL cholesterol, sometimes called “bad” cholesterol.
Although there are already approved drugs that target PCSK9 to lower cholesterol, they are not as widely used as some doctors would like. A one-and-done approach might change that.
“Gene editing could be a definitive approach that would really make a difference,” says Dr. Jorge Plutzky, director of preventive cardiology at Brigham and Women’s Hospital. “There’s a lot of basis for thinking that it should work.”
The company will first test the therapy in people with familial hypercholesterolemia, an inherited condition that affects about 1.3 million Americans and increases the risk of early-onset heart disease. If the treatment proves safe and effective, Verve may expand to broader groups of people at risk of heart disease.
Verve began the first tests of its therapy in humans in New Zealand last summer. That study is focused on gauging the safety of the therapy and finding the right dose to use. Verve is still waiting for permission from the FDA to start a similar trial in the United States. – R.C.
6. MENOPAUSE AND INFERTILITY
After puberty, women and some trans people lose about 1,000 eggs each month. As the reserve is depleted, menopause begins, making it impossible to have children without special IVF treatment, and often introducing an array of health issues affecting the bones, brain, heart, immune system, sleep, and more.
That women will experience menopause and its concomitant health risks beginning in their 40s or 50s is unavoidable, most doctors say. But if Massachusetts General Hospital researchers Dr. Patricia K. Donahoe and David Pépin and biotech entrepreneur Daisy Robinton are successful, it might not have to be that way.
The trio founded a small New York startup called Oviva Therapeutics to develop drugs based on a natural hormone called anti-müllerian hormone, or AMH, that could potentially be used as a novel contraceptive that stalls the monthly loss of eggs and maybe even delays menopause.
Robinton, the CEO of Oviva, said her company is raising money to first test the drug in women who are having trouble conceiving with in vitro fertilization. A carefully-timed use of the drug may help increase the number of eggs that IVF doctors can harvest. Studies in animals suggest that AMH might also help protect eggs that are normally lost in women who are undergoing chemotherapy.
Ultimately, Robinton hopes Oviva will make a drug that staves off menopause altogether. She has a long way to go before reaching that lofty goal, or even proving that any applications of AMH will work safely in people. But if the drug lives up to her aspirations, its impact could be enormous.
“I want to give women agency over their bodies and lives,” Robinton says. “All women get menopause, so regardless of whether you want children, this could impact your life.” – R.C.
7. SICKLE CELL DISEASE
Sixty-six years after scientists first pinpointed the genetic cause of sickle cell disease, three Massachusetts biotech companies are poised to carry the baton over the finish line of a long race to develop potentially permanent treatments.
Sickle cell is named for the crescent shape of the red blood cells in people born with the condition, which affects about 100,000 Americans and disproportionately afflicts Black people. These sickle-shaped cells are liable to form clots in tiny vessels that are so painful they can send patients to the emergency room.
The source of those woes is a single error — think of it as a typo — among the 3 billion letters that comprise the human genome. It’s buried in the gene for hemoglobin, the crucial blood protein that shuttles oxygen throughout the body. Although directly fixing the typo remains difficult, scientists have devised some clever workarounds.
One solution, a gene therapy advanced by Somerville-based Bluebird Bio, is to simply give patients a brand-new copy of the hemoglobin gene. To do that, the company harvests a person’s blood stem cells from their bone marrow, deploys an engineered virus to sneak the new gene into those cells, and then returns the altered cells to the person’s body.
In a different approach, two Boston companies, CRISPR Therapeutics and Vertex Pharmaceuticals, are using CRISPR gene editing to tweak the DNA in a patient’s blood stem cells. The therapy turns on production of the fetal form of hemoglobin, a backup of sorts that appears to compensate for the sickle form.
In clinical trials, both therapies have dramatically reduced the number of pain crises — some lasting for days — that people with sickle cell normally experience. The FDA could begin reviewing both therapies this spring, and if all goes well, an approval decision could come by the end of this year or in early 2024. – R.C.
8. ALZHEIMER’S DISEASE
No prescription drug rollout will be watched more closely in 2023 than Leqembi, a new treatment for Alzheimer’s disease from the Japanese pharmaceutical company Eisai and Cambridge-based Biogen.
The medicine moderately slowed cognitive decline by 27 percent during an 18-month trial involving nearly 1,800 people in the early stages of Alzheimer’s. It also significantly lowered levels of a protein called amyloid that forms plaque in the brains of some people with the disease, although some scientists dispute how beneficial that is. Leqembi will cost $26,500 a year for the average patient and will be administered intravenously for an hour every two weeks.
For the estimated 6 million Americans living with Alzheimer’s and their families, the Food and Drug Administration’s January 6 approval of Leqembi was a breakthrough. Two of the most widely prescribed drugs for the disease, Aricept and Namenda, are decades old and not very effective.
For Biogen, one of the first global biotechnology companies and one of the biggest employers among Massachusetts drug makers, with almost 2,300 workers, Leqembi also offers a shot at redemption. In 2021, Biogen and Eisai won approval of another Alzheimer’s drug, Aduhelm, over the objections of a panel of scientific advisers to the FDA who questioned its safety and effectiveness. Three members of the panel resigned in protest, including a Harvard professor of medicine.
The controversial approval of Aduhelm, originally priced at $56,000 a year, and its rollout proved a debacle. Medicare and private insurers refused to pay for it except in clinical trials. A recent report by two congressional committees skewered the FDA for “inappropriate” coordination with Biogen and faulted the company for its “aggressive” plans to maximize profits.
Leqembi has the potential to be a blockbuster, but only if Medicare will pay for it. A decision is expected later this year. – J.S.
9. LYME DISEASE
Twenty-one years after the only human vaccine for Lyme disease in the United States was pulled from the market, scientists are getting closer to offering a new vaccine and another preventative to keep the tick-borne illness at bay.
The effort furthest along is a partnership by the pharmaceutical giant Pfizer and a French biotech, Valneva. They have developed a vaccine that stimulates antibodies in people to fight off the disease-causing bacteria carried by ticks.
A clinical trial for the vaccine is now in the final phase and has included sites in New England. The study suffered a setback when the partners announced on February 17 that they had to drop half of the participants because of violations of the trial guidelines by a company hired to test the vaccine in the United States, not because of safety concerns with the vaccine. Pfizer, which has one of the largest workforces of drug companies operating in Massachusetts, with about 2,800 employees, nonetheless said the partners still aim to seek FDA approval in 2025.
Meanwhile, scientists from the nonprofit biotech MassBiologics — which is affiliated with the University of Massachusetts Chan Medical School — have tested a vaccine alternative on 42 volunteers. The injection contains a laboratory-made Lyme monoclonal antibody that researchers hope will provide immediate, if temporary, immunity to the disease. An early-stage trial found that Lyme PrEP was safe and protected recipients for at least seven months, longer than the typical tick season.
Although the protection fades, it comes from a single, fast-acting shot, a distinct advantage over vaccines that typically require a series of injections over several months. “We think we’re on to something important,” says Dr. Mark Klempner, a professor of medicine at the school. MassBiologics researchers plan to test Lyme PrEP in a later-stage trial within the next year but first want to license the technology to a drug company.
In 1998, the FDA approved the first Lyme vaccine, LYMErix, developed by what is now GlaxoSmithKline. It was nearly 80 percent effective, and there appeared to be relatively few side effects. But it was a commercial bust, partly because Lyme disease wasn’t regarded as a serious problem at the time. – J.S.
Untreated mental illness takes a staggering toll. Yet, the pharmaceutical industry has largely withdrawn from psychiatric drug discovery in recent decades because it’s expensive and often ends in failure.
Karuna Therapeutics, a Boston-based biotech, hopes its efforts to zig where Big Pharma has mostly zagged pay off this year. It plans to ask the FDA to approve a schizophrenia drug called KarXT that has shown encouraging results in clinical trials.
Like many other experimental drugs, KarXT is a story of promise, disappointment, and resurrection.
In the 1990s, Eli Lilly tested a compound called xanomeline on patients with Alzheimer’s disease to see if it would improve memory, according to Dr. Steve Paul, Karuna’s chief scientific officer and a former Lilly executive. It appeared to provide some benefit, but Lilly researchers noticed it dramatically reduced symptoms of psychosis, a not uncommon feature of Alzheimer’s. Unfortunately, its side effects included serious gastrointestinal problems, and Lilly shelved it.
Fast-forward to 2009, when Karuna was founded. Karuna combined xanomeline with an old compound to tame the side effects. In August, Karuna said that the combination pill, which uses a new scientific approach, reduced psychosis and related symptoms in patients with schizophrenia in a late-stage trial — and without the side effects of weight gain, drowsiness, and tremors caused by current antipsychotic drugs.
Paul says the company expects the results of another late-stage trial by March 31 but already plans to seek FDA approval based on current data. – J.S.
11. AUTOIMMUNE DISEASES
Can a single pill help clear psoriasis, extinguish inflammatory bowel disease, ease pain in psoriatic arthritis, and quell haywire immune reactions in lupus?
Takeda Pharmaceutical, the largest biopharma employer in Massachusetts, is betting $4 billion upfront that it can. That eye-popping wager, made official in February, is the price Takeda paid for a still-experimental medicine developed by the private biotech Nimbus Therapeutics, based in Boston.
The drug blocks an important cog in the immune system, an enzyme called TYK2. Some people are born with defective versions of the enzyme that actually make them far less likely to develop inflammatory or autoimmune diseases. “It’s a little bit of luck to have that,” says Nimbus CEO Jeb Keiper. His company’s drug is intended to give people with normal copies of TYK2 that same benefit.
Another pharma company, Bristol Myers Squibb, won approval for the first commercial TYK2 inhibitor last summer. That pill, Sotyktu, was approved for treating moderate-to-severe plaque psoriasis (a condition that causes patches of dry and scaly skin), but was found to have side effects, including increased risk of infections.
Takeda hopes the pill it bought from Nimbus will have fewer side effects. The drug significantly reduced skin lesions in a medium-size study of patients with moderate-to-severe plaque psoriasis, which afflicts nearly 2 million people in the United States, although its safety and effectiveness remain to be proven in a larger study slated to begin this year.
Bristol Myers Squibb and Takeda alike hope their drugs can reduce swelling and tenderness in psoriatic arthritis, and tamp down inflammation in other autoimmune conditions including Crohn’s disease, ulcerative colitis, and systemic lupus erythematosus. – R.C.
12. AMYOTROPHIC LATERAL SCLEROSIS (ALS)
In September, less than a decade after two undergraduates at Brown University came up with the idea for a drug for ALS and founded Amylyx Pharmaceuticals, the Cambridge startup got it approved and began rolling it out, although there have been lingering questions about its effectiveness.
The approval of the medication, called Relyvrio, buoyed patients with ALS, also known as Lou Gehrig’s disease, a rare and devastating neurological disorder that causes progressive paralysis and death. Since 1995, the FDA has approved only two other drugs for the disease. Neither works very well.
A small, intermediate-stage study of 137 patients showed that over 24 weeks, recipients of Relyvrio experienced a 25 percent slower decline than participants receiving a placebo — declining 2.32 points fewer on a 48-point scale that rates physical abilities, including walking, speaking, swallowing, and breathing. About 90 patients who got the drug in the trial and stayed on it for seven more months lived a median 4.8 months longer than those who got the placebo.
A panel of scientific advisers to the FDA initially recommended regulators reject the drug, citing weak evidence of its benefits. But the panel reversed itself after considering emotional pleas from patients and an analysis of additional data from Amylyx. The FDA greenlighted Relyvrio, saying patients desperately needed a new drug.
Amylyx began delivering Relyvrio in the United States in October, say cofounders Joshua Cohen and Justin Klee, but they declined to say how many patients have received it. The drug has a list price of about $158,000 per year, more than five times the highest cost recommended by the Institute for Clinical and Economic Review, a nonprofit Boston drug-pricing watchdog.
Given the dire need for an effective ALS drug — patients live only two to five years after diagnosis, on average — Amylyx is running another trial to confirm the encouraging findings of the earlier one, with results expected next year. If the outcome is negative, the company promises to pull the drug from the market.
“We’re going to do what’s right for patients,” Klee says. – J.S.
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