BridgeBio (BBIO+1.4%) launches its rolling NDA filing with the FDA seeking approval to use fosdenopterin (BBP-870/ORGN001) to treat patients with an ultra-rare inherited metabolic disorder called molybdenum cofactor deficiency type A (MoCD Type A), characterized by irreversible brain damage in newborns.
Fosdenopterin is a cyclic pyranopterin monophosphate (cPMP) substrate replacement therapy designed to reduce the buildup of toxic sulfites thereby alleviating central nervous system symptoms in MoCD Type A sufferers. It has Orphan Drug, Rare Pediatric Disease Designation and Breakthrough Therapy status in the U.S. for the indication.
Wait for it. Wait for it. That’s what the world has been doing ever since 1984 with the “it” being an effective and safe HIV vaccine. That year Margaret Heckler, then the U.S. Secretary of Health and Human Services, said in a press conference, “we hope to have a vaccine ready for testing in about two years,” and added, “”yet another terrible disease is about to yield to patience, persistence and outright genius.” Those words offered some encouragement that an HIV vaccine could have been available for use before the end of the 1980’s. Well, that prediction turned out to be off by oh about 30 years and counting. But after years of “wait for it,” there is optimism that the legendary arrival of a real HIV vaccine could happen as soon as 2021.
That’s because there are now, count them, three different late-stage human clinical trials of HIV vaccine candidates underway. That’s three more than in 1984, when scientists had just identified the human immunodeficiency virus (HIV) to be the cause of acquired immunodeficiency syndrome (AIDS). Ah, the 1980’s were a time of naive optimism in more ways than one. Identifying a virus by no means guarantees that an effective and safe vaccine can be developed anytime soon.
But here we are, after decades of disappointments, eyeing three clinical trials named HVTN 702, Imbokodo, and Mosaico. If you are wondering what HVTN is, besides being an unpronounceable string of consonants, it is an acronym for the HIV Vaccine Trials Network. Here’s where each of these three trials currently stands:
Beginning in October 2016, this is a Phase III/IIb clinical trial to study the efficacy, safety, and tolerability of a vaccine candidate called ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59. This may sound like an amazingly effective password to use but actually represents two types of intramuscular injections.
The first type includes a re-engineered canarypox virus combined with pieces of HIV that can’t cause HIV infection on their own. This is the priming part of the vaccine, the portion that primes or alerts your immune to the virus, telling your immune system, “this is your enemy, this is what you should be defending against.” It is, in a way, the canarypox in the coal mine that warns your defense system. The second type of injection consists of pieces of the protein envelope that surround the HIV along with M59, an adjuvant that uses an organic compound called squalene. An adjuvant is a substance that doesn’t on its own generate immune responses but instead can boost your immune system’s responses to parts of the virus. This is the boost part of the so-called “prime-boost” strategy. Once the the immune system is alerted to the virus, this part boosts the troops, which are your immune system’s B cells. Kind of like recruiting Captain Marvel, Ant Man, and others to the cause to fight Thanos.
The setting for the trial is South Africa, which according to UNAIDS has at least 7,700,000 people living with HIV. Already 5,400 HIV-negative adults from 18 years to 35 years old are enrolled. They will be followed for 24 to 36 months to determine if they develop any new HIV infections after enrollment. Participants will receive a series of intramuscular injections of either the vaccine or a placebo that is basically just salt water. Currently, the trial is expected to conclude July 2021. The National Institute of Allergy and Infectious Diseases (NIAID) is sponsoring this trial.
This Phase IIb study began in November 2017 and completed enrollment in May 2019 of 2,600 sexually-active women between the ages of 18 and 35 in five southern African countries: Malawi, Mozambique, South Africa, Zambia, and Zimbabwe. Like the vaccine used in HTVN 702, the vaccine for the Imbokodo Study consists of two different types of injections, albeit with different ingredients, and uses a “prime-boost” approach as well. The prime injection (called Ad26.Mos4.HIV) includes an adenovirus, a virus that typically causes the common cold, that’s been re-engineered and combined with pieces of HIV. The boost injection consists of pieces of the HIV protein envelope along with an aluminum phosphate adjuvant. Like the HVTN 702 trial, this trial will randomly assign participants to receive either the vaccine or a salt water placebo and follow them to see if they get infected with HIV in locations where HIV prevalence is high. The trial is expected to conclude February 2022. Janssen Vaccines & Prevention B.V., a division of Johnson and Johnson, is the sponsor for this trial. If you are wondering what “Imbokodo” means, it is “rock” in Zulu, the largest ethnic group in South Africa.
Unlike the other two trials, this Phase III trial will proceed in multiple sites in North America, South America and Europe rather than in southern Africa. The study just launched in July of this year and will aim to enroll 3,800 HIV-negative men and transgender people who are between 18 and 60 years old and have sex with either men or transgender people. The Mosaico trial will use the same vaccine as the Imbokodo trial. Janssen Vaccines & Prevention B.V. is the sponsor for this trial as well with NIAID providing funding. The Fred Hutchinson Cancer Research Center and the U.S. Army Medical Research and Development Command (USAMRDC) are also involved.
Pictured here are vials of the vaccine used in the HVTN 702 trial. (Photo credit should read MUJAHID … [+]
AFP VIA GETTY IMAGES
Another Reason for Optimism
By late 2020, we should have a much better sense of how at least two of these three trials are going. An additional reason for optimism is that the HVTN 702 trial is using a modified regimen and adjusted version of a vaccine candidate that showed some success in preventing HIV infections in the previous completed RV144 clinical trial. That trial, which had nothing to do with recreational vehicles, included over 16,000 study participants in Thailand and concluded in 2009. Although the findings were encouraging, showing the vaccine to reduce HIV infections by about 30%, scientists didn’t consider such a protection level high enough to merit moving forward with the vaccine as it was. They subsequently made changes bringing us to the vaccine and regimen that’s now part of HVTN 702.
Why Developing an HIV Vaccine Has Been So Challenging
While the world is closer to an HIV vaccine than it’s ever been, don’t forget that HIV is a tough, tough villain. HIV has a number of features that make it difficult to vaccinated against. One is that it doesn’t naturally stimulate enough of an immune response when it infects you. As Seth Berkley, CEO of Gavi, explained in this TED-Ed talk, HIV uses various methods to distract and hide from your immune system:
That has meant that scientists have had to find clever ways to prod your immune system to marshal its troops. Secondly, HIV is a bit like Loki or Mystique, coming in many different forms. An immune response against one form may not be effective against other forms. Third is lack of correlates of protective immunity. These are ways to measure your level of immunity against HIV. For example, if you want to check your immunity against the measles after vaccination, you can measure levels of antibodies in your blood to the measles virus. The equivalent is not there for HIV.
Finally, an HIV vaccine has to offer a high enough level of protectionc. After all, people may become more lax with other HIV prevention measures such as practicing safe sex if they believe the vaccine is supposed to offer a certain level of protection. Offering a vaccine with relatively low protective levels could be like giving you a set of clothes that may or may not dissolve. Thinking that you are fully clothed, you may blithely go to work or on a date, when, oops. A modeling study by Jan Medlock from the Carlson College of Veterinary Medicine at Oregon State University and Abhishek Pandey, Alyssa S. Parpia, Amber Tang, Laura A. Skrip, and Alison P. Galvani from the Yale School of Medicine and Yale School of Public Health and published in PNAS showed how a vaccine with 50% protective efficacy could help quell the HIV epidemic.
All of these challenges means that you should “wait for it” and see what actually happens with these three trials before making bold predictions about 2021. The world has never been closer to a real HIV vaccine. So there is indeed reason for optimism. HIV is a really tough foe, but if a vaccine can emerge that offers at least 50% protection against HIV infection along with being acceptably safe, 2021 could be legendary.
The rapid growth of UnitedHealth Group’s Optum health care services unit will contribute more than 50% of the company’s earnings in 2020, executives disclosed Tuesday.
UnitedHealth chief executive David Wichmann vowed at the start of the company’s annual investor day to continue the momentum and growth of the nation’s largest health insurer at a cumulative annual earnings growth rate of 13% to 16%. This means that the Optum unit will contribute more than 50% of total company earnings.
Optum will generate $112 billion in revenues in 2020, Wichmann said. UnitedHealth Group’s revenues will surpass $260 billion next year, the company has said.
“With more than 50% of our earnings coming from Optum in 2020, it’s a good time to reflect on the accelerating impact diversification has had on the capacities of UnitedHealth Group, now a broad-based, health care company still in its formative stages of development,” Wichmann told the investor day attendees.
While UnitedHealth continues to be the nation’s largest health insurance company, selling commercial, Medicaid and Medicare Advantage plans, its finding growth on the medical care provider side of the healthcare system. Optum owns one of the nation’s largest pharmacy benefit managers in OptumRx as well as an array of medical care provider businesses, including doctor practices, surgery centers and urgent care sites across the country.
“We believe in supporting the whole person throughout their care journey,” Andrew Witty, who is CEO of Optum and was recently promoted to president of UnitedHealth Group, told analysts and investors at the company’s annual investor day in New York.
Witty cited examples in certain markets where Optum is reducing costs, which helps the company’s overall financial growth. In New Jersey, for example, Witty said the company’s OptumCare doctor practices are “seeing 37%” fewer emergency room visits among Medicaid patients.
Meanwhile, UnitedHealth Group and its Optum medical care provider business are rolling out a combined package of medical care and health insurance as insurers meld health benefits with the provision of healthcare services. In southern California, for example, the company has unveiled a new Harmony health plan where UnitedHealth and Optum have created an “accountable care platform” that now serves 1.5 million people through value based arrangements.
Value-based models put doctors and hospitals under an umbrella that is paid based on health outcomes and performance. The goal is to make sure patients are getting the right care at the right time and in the right amount. That is contrary to the fee-for-service approach of insurance payment to doctors that is based on volume of care delivered.
On Tuesday morning, Witty said the company is working to bring Harmony to more markets including Seattle and Texas “initially.”
Medicare for All is struggling to gain traction at the national level. Some progressives are hoping that left-leaning states will instead be able to lead the way.
Last month, California Democrat Rep. Ro Khanna introduced the “State-Based Universal Health Care Act,” a bill that would let states take all the healthcare money they get from the federal government—for Medicare, Medicaid, veterans care, Obamacare, and the like—as a block grant they could use to help pay for a single-payer system.
“This bill allows states with bold leadership to establish their own successful universal health care programs in order to prove how viable our movement is on the national level,” Rep. Khanna said.
The plan comes with a host of problems. For starters, several states have already ventured down the road to single-payer—and failed to get there.
In 2011, Vermont’s then-governor Peter Shumlin signed a state-based single-payer plan into law. The idea was to get waivers to pool federal funding into a government program that would cover everyone in the state.
Three years later, Gov. Shumlin abandoned the idea after concluding it would double Vermont’s budget and require massive new taxes that he said would pose “a risk of economic shock.”
Nearly 80% of Colorado voters voted against a 2016 ballot initiative, Amendment 69, that would’ve put the state on the path to single-payer. Even the Democratic governor at the time, John Hickenlooper, urged people to vote against the initiative. Concerns about cost were a significant factor. The Colorado Health Institute analyzed the plan and found that funding would fall $8 billion short within ten years despite massive tax increases.
Rep. Khanna doesn’t think that these states’ experiences are relevant. Instead, he cites Canadian history to defend his plan. “Our neighbors in Canada established their own successful national health program by allowing the province of Saskatchewan to lead with a universal hospital care program in 1947,” he said.
In other words, ignore single-payer’s recent history in Vermont. And California. And Colorado. And look instead to Saskatchewan 70 years ago.
Canada’s healthcare system is not one the United States should wish to emulate. Consider the waits that Canadians must endure for care. The median wait time to receive treatment from a specialist following referral from a general practitioner is 19.8 weeks.
Getting to a doctor is also a tremendous challenge. More than one-third of Canadians must travel an hour or more to find a medical facility that can perform an angioplasty—a common procedure to restore blood flow through an artery—according to a 2010 study published in the journal Open Medicine. In the United States, fewer than 20% would have to go that far.
Even a trip to the emergency room in Canada doesn’t guarantee prompt care. One study found that 29% of Canadians waited four or more hours in the emergency room. In Quebec, more than half did.
In the United States, only 11% of patients had to deal with those sorts of waits.
These sorts of delays aren’t just dangerous for Canadians’ health—they’re costly. In 2018, waiting for treatment cost Canadians about $2.1 billion. And that’s only considering hours lost during the standard workday. Add on weekends and time typically spent outside the office, and the total economic cost of those waits is $6.3 billion, or more than $5,800 per person.
Canadians who can afford to opt out of those waits often do so by traveling abroad for care. In 2017 alone, patients made as many as 217,500 trips outside the country for health care, according to a report from SecondStreet.org, a Canadian think tank. They spent roughly $690 million out of pocket on care. That’s in addition, of course, to the thousands or even tens of thousands of dollars that the typical Canadian family pays in taxes to fund their country’s public healthcare system.
Rep. Khanna’s bid for state-level single-payer is unlikely to gain traction as long as Republicans control the Senate and White House. But there’s an election in less than a year that could change all that. Let’s hope Americans wake up to the fact that, they’d face long waits, rationed care, higher taxes, and a doctor shortage under single-payer.
Three pharmacy chains, including Walgreens Boots Alliance, have filed a lawsuit against drugmakers Bausch Health Inc, Assertio Therapeutics and Lupin Ltd, seeking damages for overcharging for Bausch’s diabetes drug Glumetza.
The lawsuit, filed on Monday, alleges that Assertio and Lupin struck a deal with units of Bausch to delay the entry of their generic versions of Glumetza and allowed the companies to “maintain a monopoly” in the sale of the branded drug and its generic copies.
Bausch, Assertio and Lupin did not immediately respond to Reuters’ request for comment.
Albertson Companies Inc and Kroger Inc were among the other defendants.
UnitedHealth Group projected it will generate $242 billion in revenue in 2019 and expects to report another 7% to 8% increase in top-line growth in 2020.
The insurance group presented updated figures during its investor conference that kicked off Tuesday with officials saying they expect to increase the company’s 2020 revenue to between $260 billion and $262 billion.
They project between $21 billion and $22 billion in operating earnings in 2020.
In comparison, UnitedHealth Group generated $11.98 billion in profits on $226 billion in revenue in 2018. The company is projecting to report $19 billion in profits in 2019.
The biggest driver of growth this year has been UnitedHealth’s Optum, the company’s pharmacy benefit manager. Optum revenue is projected to have increased by 11% from 2018 to 2019, earning UnitedHealth $112 billion in revenue compared to $101 billion in 2018.Optum is expected to continue to be a major growth driver for the company in its 2020 earnings projection, with UnitedHealth pegging growth to increase again between 13% to 14%.
