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Thursday, September 9, 2021

HHS aims to use value-based care payment models to lower drug prices

 The Department of Health and Human Services wants to test models that would pay drugs based on their clinical value as part of a new plan to tackle high prices.

The plan released Thursday lays out several administrative tools the agency plans to take to address high prices. It also calls on Congress to adopt several reforms such as giving Medicare price negotiation authority and cap Part D catastrophic spending.

“By promoting negotiation, competition, and innovation in the health care industry, we will ensure cost fairness and protect access to care,” HHS Secretary Xavier Becerra said in a statement Thursday.

One of the key tools that HHS aims to use is to employ payment models to curb drug prices. The agency wants to test models that use value-based payments in Medicare Part B.

The Center for Medicare & Medicaid Innovation Center can create small-scale mandatory models that could link payments for drugs and biologics to metrics that include “improved patient outcomes, reductions in healthcare disparities, patient affordability and lower overall costs,” the plan said.

Such models could extend to payers beyond Medicare, including employer-sponsored and Affordable Care Act exchange plans as well as Medicaid.

Other models may boost incentives for greater value therapies that include biosimilars and generics. These incentives could also come with an outcome-based arrangement with drugmakers.

“This approach has the potential to reduce public and private sector costs, expand the utilization of biosimilars and generics and encourage manufacturers to develop innovative new drugs—all without reducing anyone’s access to needed medicines,” the plan said.

HHS also wants to test a voluntary Part D model that gives beneficiaries a choice of Part D plans that offer “more predictable out-of-pocket costs for a broad set of formulary insulins,” according to the plan. “This model could be updated to include additional drug classes that are associated with high out-of-pocket costs for beneficiaries and have high prevalence and/or utilization within the Medicare population.”

CMMI is also considering models that would tie accountability to the total cost of care for a patient. This approach ties payments to results in changes for drug utilization, spending and outcomes.

“Models that test innovative bundled payments for a broad set of services could include incentives for care redesign to support patient engagement, enhanced care coordination and improved quality,” according to the plan.

Such a model could offer incentives for dispensing cheaper biosimilars and generics.

CMMI has approved total cost of care models before for healthcare services and a Trump administration review found that such a model in Maryland saved Medicare money.

This isn’t the first time the federal government has turned to payment models to lower drug prices. The Trump administration finalized a rule late last year that created a most-favored-nation model that tied prices for drugs reimbursed under Medicare Part B to an average paid by countries overseas. But the Biden administration has proposed nixing the model after lawsuits from the pharmaceutical industry.

The plan also renews HHS’ support for extending drug price negotiation authority to Medicare, a key policy demand of the White House. But the negotiated price could also apply to commercial and ACA plans.  

But the plan calls for Congress to adopt several other reforms that could spur greater use of biosimilars and generics. These include creating federal support for “nonprofit generic drug manufacturers that increase the availability of generic drugs,” according to the plan.

Other actions include potentially lowering the exclusivity period for biologics.

Congress can also create a cap on catastrophic coverage for Part D beneficiaries and create a beneficiary out-of-pocket cap.

The plan comes as Congress is drafting a massive $3.5 trillion infrastructure package that would add dental, vision and hearing benefits to Medicare. Democrats are exploring giving Medicare drug price negotiation authority to help pay for the package.

https://www.fiercehealthcare.com/payer/hhs-aims-to-use-value-based-care-payment-models-to-lower-drug-prices

HCA sells off dozens of newly acquired home care sites to focus on core networks

 HCA Healthcare just locked in its $400 million majority stake purchase of Brookdale Senior Living’s home health and hospice business in July, yet the hospital chain is already looking to trim off the fat with some extra dealmaking.

On Wednesday, the hospital chain announced that it has entered into a preliminary agreement with home care provider LHC Group to sell off nearly 50 home health locations, hospices and therapy agencies across 22 states.

The companies are planning to finalize the deal in the fourth quarter of 2021. LHC Group did not share the sale price in its announcement but said it expects to gain roughly $146 million in annualized revenue from the purchased assets.

For HCA, the sell-off falls in line with the chain’s primary strategy of strengthening its existing networks, William Rutherford, executive vice president and chief financial officer of HCA, explained Thursday during a virtual session of the Morgan Stanley Annual Global Healthcare Conference.

He said the initial Brookdale acquisition “was an important strategic acquisition” in that much of its existing locations were already in HCA’s active markets, allowing the chain to add new services that support existing acute, outpatient and ambulatory surgery offerings.

But outside of “a select opportunity here or there” where HCA may see a chance to enter into a new market, Rutherford said that the company has little interest in piecemeal home health offerings that fall outside of its networks.

“We believe the real value is in the network development, so our focus will continue to be in markets where we have that full range of services,” he said during the virtual session.

While the home health and hospice moves are the most recent examples of HCA’s established strategic merger and acquisition strategy, Rutherford noted that the company’s strong balance sheet offers “the capability and willingness” to keep cutting deals across acute care and other network support services.

“We’ll continue to look for acquisitions in all of those domains: our hospital acquisitions, our outpatient and ambulatory, and then to the extent there are new service opportunities we’ll evaluate that so long as they continue to meet our strategic and long-term objectives,” he said.

For now, though, HCA is not looking to spin out or sell off any major pieces of its portfolio such as its revenue cycle management business. The only exceptions, Rutherford said, would be the odd facility or two that is not contributing to the strength of an existing network, as was the case with some of its Georgia-based hospitals earlier this year.

Rutherford also fielded a handful of questions from virtual attendees related to COVID-19 and how his company is handling the disease’s apparent fourth wave.  

He said that the chain has become more seasoned in terms of managing electives, capacity and staff. Many of these disruptions would need to be handled on a facility-by-facility basis, he said, although those experiences and no signs of government-mandated shutdowns are both working in the chain’s favor.

“The experiences we’ve had during the past 18 months have really proven to help us navigate this current surge going forward,” Rutherford said.

However, there is “no question” that the labor market has been and will continue to be strained as a result of the pandemic, he said.

The executive said that the organization has an arsenal of programs and initiatives that it can lean on to weather the storm, such as its temporary staffing agency, shift-bonuses and CHIP coverage. HCA will need to be responsive with these tools in areas that face staffing drop-offs, but so far Rutherford said he has not heard of a need for any large-scale or system-wide sign-on bonuses to attract talent.

Regarding COVID-19 vaccines, the executive said that the organization has had numerous discussions on whether to require the shots as a condition of employment but has not yet taken a solid position either way. Rutherford characterized the decision as an ongoing consideration and stressed that HCA as a whole is encouraging vaccination and vaccine-supportive policies across its workforce.

Rutherford was also questioned on HCA’s view of up-and-coming trends in care delivery such as tech-enabled primary care or value-based care.

He replied that, as of now, neither of those approaches pose a major risk to the organization’s activities. He pointed to major markets in Florida and California where these players have been in play for a handful of years and highlighted HCA’s strong performances in those same regions.

Further, it’s not as if the chain is against dipping its toes into these areas at some point down the line.

“We can be really select in our response and we can partner with these entities as they unfold going forward,” he said. “And, we are developing some of those capabilities on our own, with our own employed physician network.”

https://www.fiercehealthcare.com/hospitals/hca-sells-off-dozens-its-newly-acquired-home-care-locations-to-keep-focus-its-core

Cardiff reveals early data on challenger to Amgen's KRAS crown

 Amgen has already won the KRAS race by getting Lumakras across the finish line, but Cardiff Oncology has just rolled out some early data for a follow-on candidate showing partial responses and extended survival without disease progression compared to standard of care.

Cardiff’s onvansertib is being trialed in a phase 1b/2 study in patients with metastatic colorectal cancer who have a mutation of the KRAS gene, according to a Wednesday release. The therapy is being combined with chemotherapy and Roche's stalwart Avastin. Patients must have failed on chemotherapy and or/Avastin prior to entry in the trial.

The therapy achieved an initial partial response in eight of 19 patients, or 42%, who had received the middle dose and were evaluable as of the cut-off date. The response was confirmed in seven of those patients, or 37%, after further follow-up. This compares to an objective response rate of 5% to 13% seen in historical controls of patients who received standard of care.

For all dose levels, 12 patients out of 32, or 38%, achieved a partial response and 10 out of 32, or 31%, had a confirmed response.

The trial has not yet reached a median progression-free survival, but evaluable patients have reached 9.4 months, compared to a historical length of 4.5 to 5.7 months.

Onvansertib was well tolerated, however 10% of adverse events were reported as a grade 3 or 4, meaning they required medical intervention or hospitalization. Cardiff said the events were manageable and reversible with supportive care.

Cardiff’s shares bounced on the KRAS news, rising around 20% to $8.44.

The California biotech has some stiff competition in the KRAS game. Amgen, of course, is well ahead of the pack after receiving an FDA nod for Lumakras in May for non-small cell lung cancer (NSCLC). The Big Pharma has big plans for the KRAS inhibitor, including in advanced colorectal cancer.

Another company on Amgen’s heels is Mirati, which has had an up-and-down journey getting a KRAS rival towards an FDA submission. But the biotech got a boost in June when the agency handed over a breakthrough therapy tag for adagrasib in patients with NSCLC who have a G12C mutation.

Cardiff is also testing onvansertib combinations in phase 2 studies of patients with second-line metastatic pancreatic ductal adenocarcinoma and metastatic castrate-resistant prostate cancer.

https://www.fiercebiotech.com/biotech/cardiff-reveals-early-data-challenger-to-amgen-s-kras-crown

Sanofi's $3.68B Buy Not Paying Off Yet as Autoimmune Drug Flunks Phase 3

 Paris-based Sanofi announced that its Phase III PEGASUS clinical trial of rilzabrutinib for pemphigus failed to hit the primary or key secondary endpoints. Sanofi picked up the drug when it acquired South San Francisco-based Principia Biopharma in August 2020 for $3.68 billion.

Rilzabrutinib is an oral BTK inhibitor. Pemphigus is a rare, debilitating autoimmune disorder that results in blisters on the skin and mucous membranes. The trial's primary endpoint was complete remission from weeks 29 to 37 with minimal doses of corticosteroids. The data shows that there was no significant difference between rilzabrutinib and placebo.

“While these results are disappointing, we believe the rilzabrutinib clinical program holds great potential to address the unmet treatment needs of people living with immune-mediated diseases,” said Naimish Patel, M.D., head of Global Development, Immunology and Inflammation, for Sanofi. “Our mission is to improve outcomes by exploring new scientific approaches and novel therapies to advance the standard of care. We are committed to investigating rilzabrutinib further and progressing our clinical programs forward to deliver new treatment options for patients.”

Because the BTK enzyme has a significant role in a variety of immune processes, including B cell expansion, the production of immunoglobulins, and activation of cells of the innate immune system, such as mast cells, eosinophils, and basophils, the drug has the potential for a wide range of autoimmune disease, including rheumatoid arthritis and chronic spontaneous urticaria. Sanofi is studying the drug in a Phase III trial for immune thrombocytopenia, a rare blood disease, and a Phase II trial for IgG4-related disease. The company plans for Phase II studies to begin this year in asthma, atopic dermatitis, chronic spontaneous urticaria and warm autoimmune hemolytic anemia.

When Sanofi acquired Principia, in addition to rilzabrutinib, it picked up another BTK inhibitor, ’168, which is being developed for multiple sclerosis, and PRN473 Topical, for immune-mediated diseases that would benefit from localized treatment to the skin.

Yesterday, Sanofi announced it was acquiring New York-based Kadmon Holdings for about $1.9 billion. The deal is intended to grow Sanofi’s general medicines core assets. Kadmon has a recently approved drug, Rezurock (belumosudil), a first-in-class drug for chronic graft-versus-host disease (cGVHD) for adults and pediatric patients 12 years and older who have failed at least two previous lines of systemic therapy.

“We are excited that Sanofi has acknowledged the value of Rezurock and the deep potential of our pipeline,” said Harlan Waksal, M.D., president and chief executive officer of Kadmon. “By leveraging Sanofi’s global resources and long-standing expertise in developing and commercializing innovative medicines, Rezurock is now well-positioned for global accessibility, faster. I want to thank the entire Kadmon team, including management and the Board of Directors, and the Sanofi organization, for their ongoing commitment to patients and their caregivers.”

Kadmon’s pipeline compounds include drugs for immune and fibrotic diseases and immuno-oncology treatments.

In early August, the U.S. Food and Drug Administration (FDA) approved Sanofi’s Nexviazyme (avalglucosidase alfa-ngpt) for late-onset Pompe disease in patients one year and older. Pompe disease is a progressive and debilitating muscle disorder that damages a person’s ability to move and breathe. The drug is an enzyme replacement therapy (ERT) that targets the mannose-6-phosphate (M6P) receptor.

https://www.biospace.com/article/sanofi-s-rare-autoimmune-drug-flunks-phase-iii-study/

Precision BioSciences, iECURE Ink Licensing Pact For Gene Editing Therapies

 

  • Precision BioSciences Inc (NASDAQ: DTIL) and iECURE announced a license and collaboration agreement.

  • Under the agreement iECURE plans to advance Precision's PBGENE-PCSK9 candidate into Phase 1 studies and gain access to Precision's PCSK9-directed ARCUS nuclease to develop additional gene-editing therapies for genetic diseases, initially targeting liver diseases.

  • iECURE plans to file a clinical trial application in 2022 to advance the PBGENE-PCSK9 through Phase 1 studies for familial hypercholesterolemia (FH).

  • Precision will retain rights to PBGENE-PCSK9.

  • In return, Precision has granted iECURE a license to use its PCSK9-directed ARCUS nuclease to insert genes into the well-characterized PCSK9 locus to develop treatments for four other pre-specified rare genetic diseases.

  • Precision will receive an equity stake in iECURE and is eligible to receive milestone and royalty payments.

Moderna’s mRNA Pipeline Shows No Sign of Slowing Down on R&D Day

 With the world’s second most popular COVID-19 vaccine under its belt, Moderna is clearly not content to rest on its laurels. This week, the mRNA leader followed up its announcement of a collaboration with the Institute for Life Changing Medicines (ILCM), with an update on several programs advancing in its pipeline. 

First, let’s take a look at the collaboration, which essentially amounts to a donation on the part of Moderna – because when you make a lot of money and keep it all, you begin to look impolite. On Tuesday, the company announced that it would license an asset, mRNA-3351, to ILCM with no upfront fees and no downstream payments to be developed by the latter for the treatment of Crigler-Najjar Syndrome Type 1 (CN-1). 

CN-1 is an ultra-rare genetically inherited disorder caused by a mutation in the UGT1A1 gene in which bilirubin cannot be broken down. Lacking this critical enzyme, bilirubin builds up in the body, causing damage to the brain, muscles and nerves.

It affects approximately 1 in 750,000-1,000,000 people worldwide, patients who must endure up to 14-16 hours of phototherapy treatment a day for life. The only definitive treatment is a liver transplant, which comes with its own serious risks.

Moderna Chief Executive Officer Stéphane Bancel evoked the obstacles found by extremely rare diseases in the pharmaceutical industry.

“At Moderna, we believe that mRNA therapies have the potential to profoundly impact rare disease patients and their families. Ultra-rare diseases are always a challenge for our industry given the very small number of patients who could benefit from the medicine,” he said. “We decided that rather than charge a high price for the medicine candidate, which is not aligned with our values, we would rather give it away for free.”

Moderna followed this up on Thursday with an update from its fifth annual R&D Day. Piquing possibly the most interest was the announcement of a single dose vaccine that combines a booster against COVID-19 and a booster against the flu – something of particular interest given the approaching Fall season.

“Our number one priority as a company right now is to bring to market a pan-respiratory annual booster vaccine, which we plan to always customize and upgrade," Bancel stated during the R&D focus day. 

Other significant news included positive new interim Phase I data from the company’s respiratory syncytial virus (RSV) vaccine candidate in older adults. Moderna stated that the vaccine elicited neutralizing antibodies in all participants at all dose levels with mRNA-1345 and boosted antibodies by approximately 14-fold against RSV-A and 10-fold against RSV-B. A single vaccination at each dose proved to be well-tolerated at the one-month mark. A phase II/III study is expected to begin by the end of 2021.

The company also revealed a new pediatric combination vaccine candidate (mRNA-1365) merging mRNA-1345 with its investigative hMPV vaccine. There is currently no approved vaccine to prevent RSV, which is the leading cause of severe respiratory illness in young children and older adults 65 and above, and Moderna is in competition with Pfizer, among others, to achieve the first. Pfizer’s RSV vaccine candidate recently entered Phase III.

Moderna also announced the full enrollment of several vaccine trials, highlighting a phase II study of its personalized cancer vaccine, mRNA-4157, which it is testing in combination with Merck’s Keytruda® compared to Keytruda alone, for the adjuvant treatment of high-risk resected melanoma. The primary endpoint for the study is recurrence-free survival at 12 months.

Of course, Moderna also gave updates on its COVID-19 vaccine, including variations in the works to address variants of concern Beta and Delta, and its Phase II/III trial of the vaccine in adolescents 12 to 17. Moderna has filed for emergency use approval in this age group in the U.S.

Moderna’s portfolio is comprehensive and diversified, with 37 programs in development, including 22 currently in clinical trials. 

Last month, the company announced the launch of a Phase I clinical trial for its mRNA-based vaccine against HIV. The study will assess the safety and immunogenicity of the candidate in HIV-negative adult subjects 18 to 50.  Moderna expects the trial to run until the spring of 2023.

On the therapeutic side, mRNA-3351 does not stand alone in Moderna’s rare disease pipeline. On August 23, the company announced that the first patient had been dosed in its phase I/II study of mRNA-3705, an investigational mRNA therapeutic for methylmalonic acidemia (MMA), another inherited disease in which the body cannot break down certain proteins and fats, leading to metabolic crisis.

“This is another step forward in Moderna’s mission to deliver on the promise of mRNA science to create a new generation of transformative medicines for patients,” said Dr. Ruchira Glaser, SVP and Therapeutic Area Head, Rare Disease, Autoimmune & Cardiovascular, who joined the company in January 2021.

This therapy is part of Moderna’s larger portfolio of systemic intracellular therapeutics which also includes a candidate for the treatment of Propionic acidemia, another rare autosomal recessive metabolic disorder, and a therapy for Phenylketonuria (PKU), a rare disorder caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine. 

Now that mRNA has proven its worth in the vaccine setting (by saving the world from COVID-19), hopes are understandably raised for its potential in other areas. These include replacing missing or defective proteins in genetic diseases such as CN-1 and PKU, making antibodies, and potentially even gene editing.

Already established in the areas of infectious disease and oncology vaccines, decisions like bringing on Glaser – who was previously head of clinical sciences for the respiratory and specialty areas, including rare diseases, immunology and anemia at GlaxoSmithKline – point to Moderna’s commitment to remain on the forefront of mRNA innovation. 

https://www.biospace.com/article/moderna-s-mrna-portfolio-shows-no-sign-of-slowing-down-on-r-and-d-day-/

Centessa takes a step towards a new haemophila mechanism

 Haemophilia gene therapy developers look out. New competition could be on the horizon from Centessa Pharmaceuticals’ novel project SerpinPC, which today yielded promising phase 2 results. There are reasons for caution: the dataset was small, comprising just 22 patients, with no placebo control. But an 88% reduction in all bleeds with the highest dose, 1.2mg/kg, at 12 weeks versus baseline got investors’ attention, pushing Centessa shares up 16% this morning. The group hopes that SerpinPC could become a one-size-fits-all therapy, regardless of haemophilia type, severity or inhibitor status. Centessa now needs to prove the once-monthly project’s benefit in larger registrational studies, but did not give many details during a conference call today. Thrombotic events will also be closely watched given SerpinPC’s mechanism. The project is an activated protein C inhibitor designed to restore levels of prothrombinase – this in turn generates thrombin, which is needed for blood clotting. On this point, Centessa execs said they were encouraged by unchanged levels of D-dimer, a marker of excess thrombin. Even if SerpinPC succeeds it will have a hard time catching Roche’s approved haemophilia A therapy Hemlibra, which is forecast to sell around $5bn by 2026, according to Evaluate Pharma sellside consensus.

The top-five haemophilia products in 2026
Product/projectCompanyMechanismDisease subtype2026e sales ($m)
HemlibraRoche/ChugaiAnti-factor IXa & X bispecific MAbHaemophilia A5,590
NovoSevenNovo NordiskRecombinant Factor VIIHaemophilia A & B796
Valoctocogene roxaparvovec (valrox)BiomarinAAV5 factor VIII gene therapyHaemophilia A695
KogenateBayerRecombinant Factor VIIIHaemophilia A663
IdelvionCSLFactor IX-albumin fusion proteinHaemophilia B661
Source: Evaluate Pharma.

https://www.evaluate.com/vantage/articles/news/snippets/centessa-takes-step-towards-new-haemophila-mechanism