Bluebird bio gene therapy shows sustained benefit in rare metabolic disorder

Bluebird bio (BLUE +2.0%) announces long-term results from a Phase 2/3 clinical trial, STARBEAM, evaluating gene therapy elivaldogene autotemcel (eli-cel, Lenti-D) in patients with cerebral adrenoleukodystrophy (CALD), a rare inherited metabolic disorder in which very long chain fatty acids build up in the brain damaging nerve cells.

Median follow-up was 30.0 months (range: 9.1 – 70.7 months) in 32 patients. 20 of the 32 have enrolled in a long-term follow-up study Nine others will continue to be followed in STARBEAM (not yet reached 24 months post-treatment) and two withdrew.

87% (n=20/23) of treated patients who have or would have reached month 24 of follow-up achieved the primary endpoint of being alive and free of six major functional disabilities (MFDs) at month 24. 14 subjects have at least four years’ follow-up while 10 have reached five years.

97% (n=31/32) experienced stable neurologic function score (NFS) after treatment with eli-cel, including 24 with NFS of 0 (no concerns with neurologic functions).

A 35-subject Phase 3 trial, ALD-104, is underway with an estimated completion date in February 2024.

https://seekingalpha.com/news/3610124-bluebird-bio-gene-therapy-shows-sustained-benefit-in-rare-metabolic-disorder

Provention Bio initiates Phase 2b PROACTIVE study of PRV-015

Provention Bio (PRVB +1.1%) announced the initiation of the Phase 2b PROACTIVE study of PRV-015, an anti-interleukin-15 monoclonal antibody, in adult celiac patients not responding to a gluten-free diet, a condition known as ‘Non-Responsive Celiac Disease‘.

Provention is developing PRV-015 under its 2018 collaboration with Amgen.

“PRV-015 has the potential to be the first-ever approved therapeutic for celiac disease.” stated Francisco Leon, MD, PhD, Chief Scientific Officer and Co-Founder.

https://seekingalpha.com/news/3610125-provention-bio-initiates-phase-2b-proactive-study-of-prvminus-015

FDA OKs Exact Sciences’ COVID-19 sample collection kit

The FDA has approved the emergency use of Exact Sciences’ (EXAS +2.6%) COVID-19 nasal swab home collection kit.

It has been providing testing services for the respiratory infection since April.

https://seekingalpha.com/news/3610132-fda-oks-exact-sciences-covidminus-19-sample-collection-kit

CMS Acts to Spur Innovation for America’s Seniors

Today, under President Trump’s leadership, the Centers for Medicare & Medicaid Services (CMS) issued a proposed rule that unleashes innovative technology so Medicare beneficiaries have access to the latest, most cutting-edge devices. Today’s action represents a step forward that will help demolish the existing bureaucratic barriers that have created a “valley of death” for innovative products, resulting in lag times and lack of access for America’s seniors. This proposed rule delivers on President Trump’s direction to cut government red tape so seniors can access the latest treatments, which he issued in his Executive Order on Protecting and Improving Medicare for Our Nation’s Seniors.

“President Trump is delivering on the promise he made to Americans: a better, stronger Medicare program for today and the years ahead,” said U.S. Department of Health and Human Services (HHS) Secretary Alex Azar. “This new proposal would give Medicare beneficiaries faster access to the latest lifesaving technologies and provide more support for breakthrough innovations by finally delivering Medicare reimbursement at the same time as FDA approval.”

“For new technologies, CMS coverage approval has been a chicken and egg issue. Innovators had to prove their technologies were appropriate for seniors, but that was almost impossible since the technology was not yet covered by Medicare and thus not widely used enough to demonstrate their suitability for Medicare beneficiaries,” said CMS Administrator Seema Verma. “These efforts will ensure seniors get access to the latest technologies while lowering costs for innovators. Arcane bureaucratic requirements have no business preventing seniors’ access to a technology that might save their lives.”

Today’s announcement of the Medicare Coverage of Innovative Technology (MCIT) (CMS-3372-P) proposed rule, would provide Medicare beneficiaries access to the latest medical technology faster than ever. Under current rules, FDA approval of a device is followed by an often lengthy and costly process for Medicare coverage. The lag time between the two has been called the “valley of death” for innovative products, with innovators spending time and resources on FDA approval, only to be forced to spend additional time and money on the Medicare coverage process. This represents not only an unnecessary waste of resources for innovators, but also a significant problem for America’s seniors, who are prevented access to these potentially lifesaving technologies during the existing Medicare coverage determination process.

The MCIT proposal would eliminate this lag time for both seniors and innovators. It would create a new, accelerated Medicare coverage process for innovative products that the FDA deems “breakthrough,” which FDA approves on an expedited basis and could include devices harnessing new technologies like implants or gene-based tests to diagnose or treat life-threatening or irreversibly debilitating diseases or conditions like cancer and heart disease. Under the proposal, Medicare would provide national coverage simultaneously with FDA approval, for a period of four years. After that time, CMS may reevaluate the device based on clinical and real-world evidence of improvement in health outcomes among Medicare beneficiaries. This four-year timeline would incentivize the manufacturers of these breakthrough devices to develop additional evidence regarding the applicability of their products to the Medicare population, so they might continue Medicare coverage beyond the initial four years.

Importantly, because the MCIT rule would provide national Medicare coverage for four years, it would streamline identical local coverage decisions (LCDs), promoting equal access for seniors and helping innovators focus on getting their devices to patients and clinicians.  Currently, under the LCD process, 16 Medicare Administrative Contractors (MACs) make Medicare coverage decisions on the local level – 12 for Medicare Parts A and B, and four for Durable Medical Equipment. Each MAC’s decisions apply only to that MAC’s jurisdiction. In the absence of national Medicare coverage for an innovative product, the product could be covered by a patchwork of LCDs, meaning a senior in one area could have access, while another senior in a different area would not. Additionally, to secure these LCDs, innovators can be forced to seek separate decisions from several MACs. MCIT breaks through this bureaucracy to help innovators and seniors alike. Under MCIT, breakthrough devices are given automatic national coverage for four years, simultaneous with FDA approval, meaning innovators do not need to seek coverage from the MACs.

This proposed rule would also allow Medicare to cover eligible breakthrough devices the FDA has approved for use in 2019 or 2020, giving Medicare beneficiaries immediate access to these innovative and potentially life-saving devices.

Additionally, the MCIT proposed rule would clarify the standard CMS uses to determine whether Medicare should cover a product, like a drug, device, or biologic. Under the Medicare law, the program can only pay for items or services that are “reasonable and necessary” for the Medicare population. If finalized, the MCIT proposal would clarify CMS’ definition of reasonable and necessary in regulation to give innovators a clearer understanding of CMS standards.

Today’s announcement also implements a major CMS effort to provide better customer service for innovators seeking Medicare coverage for their products. This takes the form of a coordinated, one-stop-shop internal structure that harmonizes the coverage, coding, and payment processes. This new internal coordination will help CMS better assist innovators as they seek to secure Medicare coverage and payment for their newly FDA-approved products. This effort includes a new pilot project under which knowledgeable CMS staff will guide innovators through the coverage, coding, and payment processes to cut through confusion and, ultimately, help Medicare deliver critical new technologies to seniors more quickly.

In addition to the proposed rule and the internal changes, CMS is also announcing that, in an effort to ensure certainty and clarity for stakeholders, the agency has significantly reduced a backlog of requests for National Coverage Determinations (NCDs), some of which have been on a list awaiting approval since 2014. In 2019 there were 11 NCD applications waiting for CMS review. By the end of 2020, CMS will have addressed nine of those 11. One of the remaining two is being handled by local Medicare Administrative Contractors (MACs) and the second is undergoing additional clinical trials.

Public comments on the proposed rule will be accepted until November 2, 2020.

For a fact sheet on the proposed rule (CMS-3372-P), please visit: https://www.cms.gov/newsroom/fact-sheets/proposed-medicare-coverage-innovative-technology-cms-3372-p

The proposed rule (CMS-3372-P) can be downloaded from the Federal Register at:

https://www.federalregister.gov/documents/2020/09/01/2020-19289/medicare-program-medicare-coverage-of-innovative-technology-and-definition-of-reasonable-and

https://www.cms.gov/newsroom/press-releases/cms-acts-spur-innovation-americas-seniors

Alexion up on Soliris performance bump from Novartis’ LNP023

Alexion Pharmaceuticals (ALXN +8.4%) is up on more than 50% higher volume in reaction to Novartis’ (NVS -0.1%) announcement of positive results from an open-label, Phase 2 clinical trial evaluating investigational oral treatment LNP023 in patients with paroxysmal nocturnal hemoglobinuria (PNH).

Patients receiving LNP023 as an add-on to Alexion’s Soliris (eculizumab) experienced significant reductions in lactate dehydrogenase levels, a biomarker of intravascular hemolysis, compared to eculizumab alone.

Specifically, LNP023 increased hemoglobin (Hb) by a clinically relevant 2.87 g/dL. 80% (n=8/10) achieved Hb levels greater than 12.00 g/dL (normal range: 13.5 – 17.5 g/dL for men and 12.0 – 15.5 g/dL for women) without blood transfusions. All required transfusions beforehand.

After at least six months of stable LNP023 add-on therapy, at investigators’ discretion, 70% (n=7/10) discontinued eculizumab and continued receiving LNP023 as monotherapy. All maintained Hb levels with no changes in biomarkers of disease activity and no symptoms of breakthrough hemolysis.

LNP023 is a factor B inhibitor of the alternative complement pathway, acting upstream of the C5 terminal pathway where eculizumab works.

PNH is a rare blood disorder characterized by the destruction of red blood cells (hemolytic anemia), blood clots (thrombosis) and impaired bone marrow function.

https://seekingalpha.com/news/3610155-alexion-up-8-on-soliris-performance-bump-from-novartis-lnp023

Downsides to top COVID-19 vaccines from Russia, China?

High-profile COVID-19 vaccines developed in Russia and China share a potential shortcoming: They are based on a common cold virus that many people have been exposed to, potentially limiting their effectiveness, some experts say.

CanSino Biologics’ vaccine, approved for military use in China, is a modified form of adenovirus type 5, or Ad5. The company is in talks to get emergency approval in several countries before completing large-scale trials, the Wall Street Journal reported last week.

A vaccine developed by Moscow’s Gamaleya Institute, approved in Russia earlier this month despite limited testing, is based on Ad5 and a second less common adenovirus.

“The Ad5 concerns me just because a lot of people have immunity,” said Anna Durbin, a vaccine researcher at Johns Hopkins University. “I’m not sure what their strategy is … maybe it won’t have 70% efficacy. It might have 40% efficacy, and that’s better than nothing, until something else comes along.”

Vaccines are seen as essential to ending the pandemic that has claimed over 845,000 lives worldwide. Gamaleya has said its two-virus approach will address Ad5 immunity issues.

Both developers have years of experience and approved Ebola vaccines based on Ad5. Neither CanSino nor Gamaleya responded to requests for comment.

Researchers have experimented with Ad5-based vaccines against a variety of infections for decades, but none are widely used. They employ harmless viruses as “vectors” to ferry genes from the target virus – in this case the novel coronavirus – into human cells, prompting an immune response to fight the actual virus.

But many people already have antibodies against Ad5, which could cause the immune system to attack the vector instead of responding to the coronavirus, making these vaccines less effective.

Several researchers have chosen alternative adenoviruses or delivery mechanisms. Oxford University and AstraZeneca based their COVID-19 vaccine on a chimpanzee adenovirus, avoiding the Ad5 issue. Johnson & Johnson’s candidate uses Ad26, a comparatively rare strain.

Dr. Zhou Xing, from Canada’s McMaster University, worked with CanSino on its first Ad5-based vaccine, for tuberculosis, in 2011. His team is developing an inhaled Ad5 COVID-19 vaccine, theorizing it could circumvent pre-existing immunity issues.

“The Oxford vaccine candidate has quite an advantage” over the injected CanSino vaccine, he said.

Xing also worries that high doses of the Ad5 vector in the CanSino vaccine could induce fever, fueling vaccine skepticism.

“I think they will get good immunity in people that don’t have antibodies to the vaccine, but a lot of people do,” said Dr. Hildegund Ertl, director of the Wistar Institute Vaccine Center in Philadelphia.

In China and the United States, about 40% of people have high levels of antibodies from prior Ad5 exposure. In Africa, it could be has high as 80%, experts said.

HIV RISK

Some scientists also worry an Ad5-based vaccine could increase chances of contracting HIV.

In a 2004 trial of a Merck & Co Ad5-based HIV vaccine, people with pre-existing immunity became more, not less, susceptible to the virus that causes AIDS.

Researchers, including top U.S. infectious diseases expert Dr. Anthony Fauci, in a 2015 paper, said the side effect was likely unique to HIV vaccines. But they cautioned that HIV incidence should be monitored during and after trials of all Ad5-based vaccines in at-risk populations. FILE PHOTO: A scientist works inside a laboratory of the Gamaleya Research Institute of Epidemiology and Microbiology during the production and laboratory testing of a vaccine against the coronavirus disease (COVID-19), in Moscow, Russia August 6, 2020. The Russian Direct Investment Fund (RDIF)/Handout via REUTERS

“I would be worried about the use of those vaccines in any country or any population that was at risk of HIV, and I put our country as one of them,” said Dr. Larry Corey, co-leader of the U.S. Coronavirus Vaccine Prevention Network, who was a lead researcher on the Merck trial.

Gamaleya’s vaccine will be administered in two doses: The first based on Ad26, similar to J&J’s candidate, and the second on Ad5.

Alexander Gintsburg, Gamaleya’s director, has said the two-vector approach addresses the immunity issue. Ertl said it might work well enough in individuals who have been exposed to one of the two adenoviruses.

Many experts expressed skepticism about the Russian vaccine after the government declared its intention to give it to high-risk groups in October without data from large pivotal trials.

“Demonstrating safety and efficacy of a vaccine is very important,” said Dr. Dan Barouch, a Harvard vaccine researcher who helped design J&J’s COVID-19 vaccine. Often, he noted, large-scale trials “do not give the result that is expected or required.”

https://www.reuters.com/article/us-health-coronavirus-vaccines-adenoviru/scientists-see-downsides-to-top-covid-19-vaccines-from-russia-china-idUSKBN25R19H

FSD Pharma files IND for FSD201 to treat COVID-19 patients

FSD Pharma (NASDAQ:HUGE) has submitted to the FDA an Investigational New Drug Application (IND) for the use of FSD201 (ultramicronized palmitoylethanolamide, or ultramicronized PEA) to treat COVID-19 (the “FSD201 COVID-19 Trial”).

The trial will assess the efficacy and safety of FSD201 dosed at 600mg or 1200mg twice-daily together with standard of care (SOC) compared to SOC alone in hospitalized patients with documented COVID-19 disease.

Additionally, the Board of Directors has authorized the issuance of an additional 369,255 class B subordinate voting shares to certain of the company’s directors, officers, employees and consultants.

Dr. Raza Bokhari acquired 805,802 Class B Shares in lieu of compensation for his services as CEO and Executive Co-Chairman. As a result, he now owns ~8.5% of the Class B shares, in addition to 33.3% of the outstanding Class A multiple voting shares. In aggregate, he controls ~23% of the voting rights attached to the issued and outstanding FSD shares.

Previously: FSD Pharma rockets on FDA approval of FSD-201 trial to treat COVID-19 patients (June 3)

https://seekingalpha.com/news/3609970-fsd-pharma-files-ind-for-fsd201-to-treat-covidminus-19-patients