Search This Blog

Thursday, December 20, 2018

Texas ACA ruling complicates politics of Medicaid expansion


A Texas federal judge’s ruling Friday invalidating the Affordable Care Act could create political headaches for Medicaid expansion supporters in states that are moving to implement or maintain expansion.
If it’s upheld on appeal, which is highly uncertain, U.S. District Judge Reed O’Connor’s decision declaring the entire ACA unconstitutional would eliminate federal authorization and funding for the expansion of Medicaid to low-income adults. That would force states to shoulder the full price of covering people who would not qualify for coverage under pre-ACA criteria, rather than having the federal government pick up 90% of the cost.
Lawmakers and hospital association leaders in states moving toward expansion, including Idaho, Kansas, Nebraska, and Utah, worry that opponents will cite the ruling as a reason not to push forward. Expansion advocates have similar anxieties in Alaska and Montana, where Republican elected officials hostile to expansion are considering whether to continue their states’ expansion program.
The ruling strengthens the hand of Republicans pushing to add work requirements to any expansion program. It could even prompt officials in some of the 30 other states that have expanded Medicaid to reconsider their programs. Many states have statutory provisions automatically ending their expansion program if the federal government reduces its contribution.
“We could see red flags re-ignite for state and local governments because the funding rules for traditional Medicaid could once again be put into play,” said Eric Kim, a director at Fitch Ratings.
In Nebraska, where voters approved a binding ballot initiative in November to expand Medicaid, Republican state Sen. John McCollister, who supports expansion, predicted that many of his GOP colleagues, along with Republican Gov. Pete Ricketts, will point to the court ruling to try to delay or halt implementation.
“Most Republicans will use it as an excuse not to implement it until the legal situation is more firmly established,” he said. “This could be a serious setback for expansion.”
On the other hand, Nebraska state Sen. Adam Morfeld, a Democratic expansion supporter, said the ruling makes no difference because the ballot initiative enshrined expansion as a statute.
“To stop this from happening, they’d have to repeal it,” he said. “And they’re not going to repeal it because they don’t have the votes. If they don’t fund it, I’ll file a lawsuit and force them to. One way or another we’ll get this implemented.”
Ricketts’ office did not return a call for comment.
In Kansas, where former Republican Gov. Sam Brownback vetoed the GOP-controlled Legislature’s bill last year to expand Medicaid, expansion has a fighting chance in 2019 with the election of pro-expansion Democrat Laura Kelly as the new governor. But advocates there also predict opponents will seize on the Texas ruling to argue against expansion.
“They will reach for anything to use as an excuse, and this will definitely be part of their toolkit,” said state Sen. Barbara Bollier, an expansion supporter and retired physician who recently switched from the Republican to the Democratic Party.
Tom Bell, CEO of the Kansas Hospital Association, lamented the fresh uncertaintythe ruling creates, and expects opponents to cite it as a reason not to move ahead. But he sees it as a weak excuse because he believes Congress will preserve Medicaid expansion in the unlikely event the ruling stands.
“We’ve had six years of people giving us excuses about why we shouldn’t move ahead, and this will probably be the latest,” Bell said. “People said every year the ACA will be repealed. It’s never happened, and I don’t think it’s going to happen this time, either.”
Idaho state Sen. Fred Martin, a Republican who backs expansion, said O’Connor’s ruling “absolutely will be a potent argument for Republicans to stop expansion,” even though 61% of Idaho voters approved the ballot initiative. “This gives them more ammunition because it raises doubts about the future,” he said.
But he’s less worried than expansion advocates in other states because expansion has already been signed into law in Idaho, to take effect Jan. 1, 2020. That gives the Legislature and the governor more time to watch how the legal process plays out.
“Because of the time we have, for me it’s not a major factor at this time,” Martin said. That could change, however, if the 5th U.S. Circuit Court of Appeals upholds O’Connor’s decision and the Supreme Court takes the case, he added.
A spokesman for Republican Gov. Gary Herbert in Utah, where voters also approved a binding Medicaid expansion ballot initiative, said the administration is moving forward with expansion regardless of the Texas ruling. O’Connor’s decision has no immediate effect while the appeal is pending, he noted.
In Alaska, newly elected Republican Gov. Mike Dunleavy, an opponent of the state’s expansion pushed through by Independent Gov. Bill Walker, has said he will conduct an impartial review of the program with an eye to reducing its costs. His office did not return a call about the Texas ruling.
Becky Hultberg, CEO of the Alaska State Hospital and Nursing Home Association, said it’s possible that GOP lawmakers will use the court decision to discourage the governor from doing that review and urge him instead to simply roll back the expansion. “But we trust he will follow through on his promise,” she said. “We believe that’s the responsible course of action.”
In Montana, the Republican-controlled Legislature has to decide whether to renew that state’s expansion, which was spearheaded by Democratic Gov. Steve Bullock and which expires in June. A hospital association-backed ballot initiative to extend the expansion and fund it with a tobacco tax lost in November.
Now, legislative Republican leaders are discussing renewing it with the addition of a work requirement and other personal-responsibility features, but the outcome is uncertain. State Senate President Scott Sales said the Texas ruling “gives more ammunition to those of us who don’t think expansion is fiscally responsible or sustainable.”
Still, he predicted a bill renewing expansion will pass. By strengthening the position of expansion foes, the court ruling will provide greater political leverage to moderate Republicans trying to convince Democrats that adding a work requirement is necessary to save the expansion.
“It will make the debate that much more robust,” Sales said.

Down but Not Out: 10 Biggest Drug Trials That Saw Challenges in 2018


The most commonly stated statistic about clinical trials is that for every one drug on the market, there are nine that failed. A look back through 2018 indicates there were a great many successes, but plenty of challenges as well. Here’s a look at 10 notable drug challenges of the year.
#1. Takeda and Zinfandel and Alzheimer’s. On January 25, 2018, Takeda Pharmaceutical and its development partner Zinfandel Pharmaceuticals gave up on their five-year Phase III TOMORROW trial after an interim analysis. They were evaluating pioglitazone in mild cognitive impairment due to Alzheimer’s disease. The TOMMORROW trial was evaluating the genetic-based biomarker risk assignment algorithm (BRAA) in addition to the safety and efficacy of the drug. The safety was generally considered fine, but there was inadequate treatment effect.
#2. Boehringer Ingelheim and Alzheimer’s. Unfortunately, Alzheimer’s failures are the norm, rather than the exception. On February 9, 2018, Boehringer Ingelheim indicated it was abandoning its Phase II compound BI 409306 after it failed to meet its endpoints. The drug, a PDE9 inhibitor, being used to treat patients with cognitive impairment and memory dysfunction in schizophrenia and Alzheimer’s, failed to show superiority over placebo in cognition in two separate clinical trials.
#3. Merck & Co. and Alzheimer’s. Yes, well, it does seem like a theme. On February 14, Merck & Co. said it was halting protocol 019, its APECS Phase III clinical trial of verubecestat (MK-8931) in Alzheimer’s. An external Data Monitoring Committee (eDMC) had recommended ending it after an interim safety analysis, saying the likelihood of benefits didn’t outweigh the risks. Verubecestat is a BACE inhibitor, a precursor to amyloid-beta.
#4. Celgene and Multiple Sclerosis (MS). This particular failure was a bit of a surprise. On February 28, the U.S. Food and Drug Administration (FDA) hit Celgene with a Refusal to File letter over its New Drug Application (NDA) for multiple sclerosis treatment ozanimod. What was surprising was the Refusal to File was over the “nonclinical and clinical pharmacology sections” in the NDA, claiming they were insufficient for the agency to go ahead with the approval process. This was more than a bit unexpected for a company with the reputation and size of Celgene, suggesting that the application wasn’t really ready to go to the agency.
Several months later, in June, the company sort of admitted it was their fault, although at the same time, the company’s president of hematology and oncology, Nadim Ahmed, seemed to throw their Receptos unit under the bus, blaming them for the failure. Celgene acquired Receptos in 2015. The NDA for ozanimod was submitted toward the end of 2017, after it reported positive data from the second pivotal Phase III trial, RADIANCE, which was announced in May 2017.
On October 10, Celgene reported positive data from two post hoc analysis from the Phase III SUNBEAM and RADIANCE Part B trials, evaluating ozanimod in MS. The company indicates it plans to file again in 2019.
#5. Incyte and Melanoma. On April 6, Incyte Corporation revealed that its IDO1 drug in combination with Merck’s Keytruda did not meet its endpoints in a Phase III melanoma trial. The drug, epacadostat, did not improve rates of progression-free survival in the patient population compared to Keytruda alone.
#6. vTV Therapeutics and Alzheimer’s. On April 10, vTv Therapeutics announced its azeliragon failed to meet either co-primary efficacy endpoint in its Phase III STEADFAST clinical trial in patients with mild Alzheimer’s disease. It was made up of two independent, but identical double-blind, placebo-controlled trials, Part A and B. The group in Part A that received the drug showed a 4.4-point decline from baseline in the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and a 1.6-point decline from baseline in the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) compared to declines in the placebo groups of 3.3 and 1.6, respectively. They were not clinically significant changes. Azeliragon is an orally active small-molecule antagonist of advanced glycation endproducts (RAGE).
#7. Roche and Exelixis and Colorectal Cancer. On April 11, Roche temporarily halted recruiting patients to its Phase II MODUL clinical trial for metastatic colorectal cancer after four patient deaths. The patients were receiving Tecentriq (atezolizumab) in combination with Exelixis’ MEK inhibitor Cotellic (cobimetinib). Then, in mid-May, the two companies’ IMblaze370 Phase III clinical trial of Tecentriq and Cotellic failed in a comparison to Bayer’s Stivarga (regorafenib) in colorectal cancer patients who had failed at least two rounds of chemotherapy.
#8. Johnson & Johnson and Alzheimer’s. On May 18, Johnson & Johnson’s Janssen division halted its clinical trials of atabacestat, a BACE inhibitor, for Alzheimer’s disease. It was ending the program over safety issues, rather than efficacy. Patients in the EARLY Phase IIb/III clinical trial with preclinical Alzheimer’s disease, as well as a Phase II long-term safety trial, had elevated liver enzymes. EARLY launched in 2015 and was scheduled to wrap in 2024.
#9. Sarepta Therapeutics and Duchenne Muscular Dystrophy (DMD). On September 21, the European Medicines Agency (EMA) rejected Sarepta’s application for Exondys 51 for DMD. What is most notable about this was that in September 2016, the FDA approved the drug after a contentious and dramatic battle that involved internal conflict at the agency, media coverage and members of Congress and panels of DMD experts sending public letters urging approval. The application to the EMA was based on two clinical trials in 12 boys with DMD between the ages of 7 and 13.
The European agency, in its negative opinion by the Committee for Medicinal Products for Human Use (CHMP), expressed doubts about the evidence, especially related to the studies’ small size, use of historical data, and lack of comparison data beyond 24 weeks. These were essentially the same controversies within the FDA.
Meanwhile, Exondys, approved in the U.S., has a yearly price tag, based on the patient’s body weight, of approximately $300,000.
#10. Alkermes and Depression—Stay Tuned! On November 2, two FDA advisory committees voted down the company’s NDA for ALKS-5461 for depression. In total, the committees voted 21 to 2 against recommending the drug. They also voted 20 to 3 that the company had not provided substantial evidence that supports the efficacy of ALKS-5461.
One of the committee members, Martin Kulldorff, a professor of population medicine and a biostatistician at Harvard Medical School, said, “I don’t think there’s evidence that this drug works.”
The drug has had a tumultuous history. The FDA accepted the NDA in April only a few weeks after initially rejecting it due to “insufficient evidence of overall effectiveness for the proposed indication.” In its Refusal to File letter, the FDA said the company would likely have to launch additional clinical trials in order to support a resubmission. But then the FDA changed its mind and Alkermes said it did not submit any additional data to the agency as was originally suggested.
The FDA is not required to follow the recommendations of its advisory committees, although with such a strong rejection by two Adcoms, it would be surprising if it did approve the drug. The agency has a target action date of January 31, 2019 for approval.

Celgene In-licenses First Two Dragonfly TriNKET™ Immunotherapy Candidates


Dragonfly Therapeutics, Inc. (“Dragonfly” or the “Company”), announced it has licensed two TriNKET™ immunotherapy drug candidates to Celgene Corporation and its affiliates (“Celgene”) for $12m each plus prospective milestones and royalties. The licenses represent the first two of four hematological cancer targets from the companies’ June 2017 collaboration. The announcement follows recent news of an expansion of the June 2017 collaboration providing Celgene with the option to license products for an additional four-targets, increasing the total number of collaboration targets between the companies to eight (see also Dragonfly Therapeutics Inc.).
“These licenses provide Celgene exclusive worldwide intellectual property rights to the first two products developed for Celgene using Dragonfly’s TriNKET technology” said Rupert Vessey, FRCP DPhil, President of Research and Early Development for Celgene Corporation. “Based on the evidence we’ve seen, we believe these TriNKET drug candidates offer an exciting opportunity to help cancer patients by offering a novel mechanism of action in immune oncology.”

Sanofi: Philippines may decide on sale of Dengvaxia today


Whether the controversial anti-dengue vaccine Dengvaxia will be made available in the local market again is likely to be known today. Health Undersecretary Eric Domingo said the Food and Drug Administration (FDA) is set to meet today and may decide on whether to grant a certificate of product registration (CPR) for Dengvaxia.
“I was informed by FDA that they will meet Dec. 21 and may probably decide then,” Domingo said.
If the French drug manufacturer Sanofi Pasteur is able to secure a CPR, Domingo said, Dengvaxia would be available again in drugstores and pharmacies in the country. Sanofireported that last October, the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) had approved the use of the dengue vaccine in European endemic areas.
However, Domingo said, the Department of Health (DOH) is no longer resuming the dengue immunization campaign even if the FDA grants CPR for Dengvaxia. “Dengvaxia is no longer included in the DOH’s immunization program,” Domingo said.
The FDA suspended the CPR of Dengvaxia shortly after Sanofi officials admitted that the vaccine posed serious health risk to those who were not previously infected with dengue. The FDA also noted that the Dengvaxia manufacturer failed to comply with post marketing authorization requirements after securing the CPR.
Health Secretary Francisco Duque III also suspended the Dengvaxia immunization program after a number of deaths were linked to the anti-dengue vaccine. About 800,000 school children have been vaccinated during the immunization campaign.
Sanofi agreed to refund P1.16 billion for the unused doses of Dengvaxia.

Bristol Myers, Vedanta Clinical Collaboration on Cancer Combo


Bristol-Myers Squibb Company (NYSE: BMY) and Vedanta Biosciences announced a clinical trial collaboration to evaluate Bristol-Myers Squibb’s programmed death-1 (PD-1) immune checkpoint inhibitor Opdivo (nivolumab) in combination with Vedanta Biosciences’ VE800, a rationally-defined human bacterial consortium, in patients with advanced or metastatic cancers (see also Vedanta Biosciences).
In a range of preclinical models of cancer, including those sensitive and resistant to checkpoint inhibition, VE800 was shown to induce CD8+ T cells, potentiate the immune system’s attack of tumor cells, and significantly amplify the effects of anti-PD-1 therapy. These models support clinical research to explore whether modulating the microbiome with VE800 has the potential to broaden the efficacy of checkpoint inhibitors.
“Our lead, microbiome-based immuno-oncology candidate, VE800, is based on work conducted in collaboration with our co-founder, Dr. Kenya Honda, showing in preclinical models that certain gut-dwelling bacterial strains potentiate cytotoxic CD8+ T cells and enhance infiltration into tumors,” said Bernat Olle, Ph.D., Co-founder and Chief Executive Officer of Vedanta Biosciences. “Through this collaboration our goal is to determine whether VE800 in combination with Opdivo can improve outcomes for patients with advanced or metastatic cancers.”
“We are continuing to explore the novel mechanisms of new assets in combination with our oncology portfolio,” said Fouad Namouni, M.D., head of development, oncology, Bristol-Myers Squibb. “Vedanta Biosciences is a leading company focused on the characterization of immunomodulatory human gut commensals and the development of live bacterial products for the potential treatment of human diseases. Our collaboration with Vedanta Biosciences will allow us to gain a deeper understanding about the emerging microbiome landscape, its role in oncology, and the potential to improve outcomes for patients with advanced or metastatic cancer.”
“Checkpoint inhibitors, particularly PD-1 antibodies, have been a major advance in cancer therapy; however, a large proportion of patients either do not respond or have response of brief duration to those new therapies,” said Jeffrey Weber, M.D., Ph.D., Deputy Director, Laura and Isaac Perlmutter Cancer Center and Professor of Medicine, NYU Langone Health. “Alteration of the gut microbiome could play a significant role in enhancing the effectiveness of checkpoint inhibitors, and with increased understanding may also be used to select for patients who would benefit most from these immunotherapies.”
In conjunction with this collaboration, and subject to the completion of due diligence, the negotiation by the parties of definitive transaction agreements and the receipt by Bristol-Myers Squibb of all requisite approvals, Bristol-Myers Squibb currently intends to make an equity investment in Vedanta Biosciences. Vedanta Biosciences will maintain control of its VE800 program, including global R&D and commercial rights. About OpdivoOpdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers. Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

Analysts get more constructive on health insurers Cigna, Humana


In a research note to investors, Citi analyst Ralph Giacobbe added Cigna (CI) to his firm’s Focus List and made the stock a Top Pick as he sees 50% return potential in two years. Meanwhile, his peer at JPMorgan also called Cigna a top idea to own into the 2019 JPMorgan Healthcare conference and upgraded Humana (HUM) to Overweight after the recent pullback in the shares, and given Humana’s accelerating market share gains, its Medicare Advantage exposure and balance sheet.
CITI ADDS CIGNA TO FOCUS LIST: Citi’s Giacobbe added Cigna to his firm’s Focus List and made the stock a Top Pick. The analyst believes Cigna offers “compelling” value at current levels as it trades at a 27% discount to peers and a 20% discount to the market. Further, Giacobbe argued that the Express Scripts (ESRX) transaction, coupled with Cigna’s administrative services concentration and its “funding agnostic, transparent, aligned model,” should allow incremental opportunities for growth, particularly within the national account book. Overall, the analyst sees Cigna shares offering potential for 50%-plus return in the next two years. Citi has a Buy rating on Cigna’s stock. Meanwhile, JPMorgan analyst Gary Taylor told investors in a research note of his own that Cigna is his top short-term idea to own into the 2019 JPMorgan Healthcare Conference. The analyst anticipates Cigna at the conference will be prepared to provide “at least high-level combined-company proforma 2019 guidance.” Further, Taylor noted that he sees a “valuation catalyst” in the closing of the Express Scripts deal. The analyst reiterated an Overweight rating and $250 price target on Cigna’s shares.
JPMORGAN SAYS BUY HUMANA: In a research note to investors this morning, JPMorgan’s Taylor upgraded Humana to Overweight from Neutral and named the stock one of his best ideas for 2019. The analyst cited the “significant” recent stock pullback, accelerating market share gains, attractive Medicare Advantage exposure and a conservative balance sheet. Medicare Advantage demonstrated the most stable MLR during the Financial Crisis and should post strong relative earnings performance in a future recession, he added. The analyst also lowered his price target on the shares to $333 from $354.

Analysts bullish on Immunomedics after short report on manufacturing issues


Commenting on today’s weakness in Immunomedics (IMMU) shares, Wells Fargo analyst Jim Birchenough told investors that he believes the stock came under “significant” pressure on apparent concerns regarding potential observations at the company’s manufacturing facility and implications for approval of its antibody drug conjugate therapeutic sacituzumab govitecan. However, the analyst argued that the observations appear to be “old news” and that Immunomedics remains confident in sacituzumab approval odds. Voicing a similar opinion, his peer at Guggenheim added that the weakness on FDA Form-438 worries has been “overdone.”
WEAKNESS IN SHARES ‘OVERDONE’: In a research note to investors, Wells Fargo’s Birchenough attributed Thursday’s pressure on Immunomedics shares to concerns regarding potential observations at the company’s manufacturing facility and implications for approval of sacituzumab govitecan for triple negative breast cancer by its PDUFA date of January 18. However, after speaking to management, the analyst said they indicated that the Food and Drug Administration’s observations occurred as part of a pre-approval inspection in early August, are “old news” and that a remediation has long been put in place. He added that the company “appears confident” in the prospects for approval of sacituzumab govitecan and reiterated an Outperform rating on the shares. Voicing a similar opinion, Guggenheim analyst Michael Schmidt told investors in a research note of his own that he views Thursday’s weakness in Immunomedics’ stock following a short report that highlighted the company’s receipt of an FDA Form-483 on manufacturing issues regarding sacituzumab as “overdone.” The analyst also reiterated a Buy rating on the shares. Also commenting on the short report, Morgan Stanley analyst Matthew Harrison said he appreciates the concern in the market, given that investors have been worried about manufacturing issues potentially impacting the approval of IMMU-132. However, Harrison noted that he still believes there is a higher probability of approval than not on the PDUFA. The analyst reiterated an Overweight rating and $38 price target on Immunomedics’ shares.