Humacyte, Inc. (Nasdaq: HUMA), a clinical-stage biotechnology platform company developing universally implantable, bioengineered human tissues at commercial scale, has been granted the U.S. Food and Drug Administration’s (FDA’s) Regenerative Medicine Advanced Therapy (RMAT) designation for patients with advanced peripheral artery disease (PAD). This RMAT designation is granted at the same time as FDA cleared a new Investigational New Drug (IND) application for the PAD indication for Humacyte’s investigational Acellular Tissue Engineered Vessel (ATEV), formerly referred to as the “HAV”. The RMAT designation is designed to provide pathways for expedited development and review of regenerative medicine therapies for serious or life-threatening diseases or conditions. The designation allows for close interactions with the FDA and potentially an expedited/priority review of a Biologics License Application (BLA). This is the third RMAT designation granted by the FDA for Humacyte’s ATEV, in addition to previous RMAT designations for vascular trauma repair and arteriovenous (AV) access in hemodialysis.
Monday, July 1, 2024
Eisai Assumes Sole Responsibility for ADC After Collaboration With Bristol Ends
Eisai announced on Monday that Bristol Myers Squibb has ended their global strategic agreement and the Japanese pharma will now exclusively own and be responsible for the investigational antibody-drug conjugate farletuzumab ecteribulin.
With the termination of the collaboration, Eisai will “solely conduct the global development and commercialization” of farletuzumab ecteribulin, which is currently being assessed in a Phase I/II study in solid tumors. The antibody-drug conjugate (ADC) is also in a Phase II trial for ovarian, peritoneal and fallopian tube cancers, as well as a mid-stage study for non-small cell lung cancer.
Eisai will “accelerate” the development of farletuzumab ecteribulin and treat it as a high priority to “deliver it to patients as early as possible,” according to the pharma.
As part of the termination, Eisai will also refund BMS $200 million, which represents the unused portion of the initial R&D funds it received under the original agreement. The Japanese multinational will “record the remaining as other income.”
Eisai and BMS first announced their global collaboration in June 2021, which saw the New Jersey pharma pay $650 million upfront plus the $200 million sum meant to shoulder Eisai’s R&D expenses. Under the deal, Eisai was also eligible for up to $2.45 billion in development, regulatory and commercial milestones.
In return, BMS received the right to jointly develop and commercialize farletuzumab ecteribulin—which at the time was still called MORAb-202—in selected territories including the U.S., Canada, Europe, Japan and China.
The decision to assume sole responsibility for farletuzumab ecteribulin is due to BMS’ “ongoing portfolio prioritization efforts,” according to Eisai’s announcement. In its first quarter 2024 business report, BMS announced that it was launching a sweeping “strategic productivity initiative” aimed at cost savings of $1.5 billion by the end of 2025.
The strategic realignment includes around 2,200 layoffs, optimizing operations and pipeline cuts, though at the time farletuzumab ecteribulin wasn’t among the candidates that the pharma decided to drop.
Farletuzumab ecteribulin is an investigational ADC that uses a humanized IgG1 monoclonal antibody targeting the FRα protein, which is highly expressed in several types of cancers. The ADC’s toxic payload is eribulin, an inhibitor of microtubule dynamics. When released inside cancer cells, eribulin prevents cell division and can trigger cell death.
Eisai’s ADC also exerts a bystander effect on nearby cancer cells, providing an anti-tumor effect on neighboring malignant cells that might not express FRα.
Supreme Court’s Chevron Doctrine Ruling Could Limit FDA’s Regulatory Authority
The U.S. Supreme Court on Friday in a 6-3 vote overturned the decades-old Chevron deference doctrine, which could have far-reaching implications for the FDA and its regulatory functions.
The Chevron deference, dating back to 1984, requires courts to defer to federal agencies and their interpretation of statutes as long as the court agrees that the said statutes were ambiguous. The doctrine gave federal agencies strong protection from legal challenges to its actions and discouraged companies from filing complaints.
In the opinion for the majority, Chief Justice John Roberts argued that the Chevron doctrine goes directly against the text of the Administrative Procedure Act, which holds that courts should be the arbiters of all relevant questions of law—not federal agencies.
Chevron “demands that courts mechanically afford binding deference to agency interpretations, including those that have been inconsistent over time,” Roberts wrote, adding that ambiguities in the law does not signal the Congress’ intent “that an agency, as opposed to a court, resolve the resulting interpretive question.”
In overruling Chevron on Friday, the Supreme Court ushered in a new framework, dubbed Loper Bright. Courts are now required to “exercise their independent judgement in deciding whether an agency has acted within its statutory authority” and “may not defer to an agency interpretation of the law simply because a statute is ambiguous.”
This new framework could have significant consequences for the FDA and its regulatory authority, according to an analysis by global law firm Sidley.
The firm contends that Loper Bright could potentially open the regulator’s drug approvals to legal challenges. Companies need to provide “substantial evidence” that their drug candidates are safe and effective before securing approval, but courts in the past have found this ambiguous and have allowed the FDA to ask for additional requirements, such as data showing that the candidate’s effects are clinically meaningful, according to Sidley.
Under Loper Bright, more companies could try and challenge this approach, Sidley warned.
The overturning of Chevron could also pose some jurisdictional questions for the FDA, which is typically given the leeway to decide what constitutes a dietary supplement or a device product. These kinds of determinations affect how products are regulated, produced, or imported—and companies can now mount stronger challenges to this function by the FDA.
In her dissent opinion, Justice Elena Kagan noted that courts do not have the technical expertise to settle certain ambiguities.
“Some interpretive issues arising in the regulatory context involve scientific or technical subject matter. Agencies have expertise in those areas; courts do not,” she wrote. “Some demand a detailed understanding of complex and interdependent regulatory programs. Agencies know those programs inside-out; again, courts do not.”
Lpngboard Breakthrough Therapy Designation for Seizure Med
-Longboard Pharmaceuticals, Inc. (Nasdaq: LBPH), a clinical-stage biopharmaceutical company focused on developing novel, transformative medicines for neurological diseases, today announced that the FDA has granted Breakthrough Therapy designation for its investigational drug bexicaserin for the treatment of seizures associated with Developmental and Epileptic Encephalopathies (DEEs) for patients two years of age or older.
Senti Bio Awarded California Institute for Regenerative Medicines (CIRM) Grant for CAR-NK Cell Therapy
Senti Biosciences Inc
The company says SENTI-202 is an investigational cell therapy for treating relapsed/refractory hematologic malignancies, including acute myeloid leukemia (AML). The ongoing Phase 1 trial aims to provide initial efficacy data by the end of 2024 and durability data in 2025.
The trial, enrolling adult patients with specific hematologic malignancies in the US and Australia, evaluates two dose levels of SENTI-202 cells administered in cycles after disease-specific conditioning.
SNTI has a 52-week high of $1.09 and a 52-week low of $0.21.
AstraZeneca files rival to Pemgarda for COVID PrEP
AstraZeneca may have exited the COVID-19 vaccine market, but it is still hoping to protect vulnerable patients with its antibody sipavibart for pre-exposure prophylaxis (PrEP).
The drugmaker said this morning that an application for sipavibart (AZD3152) has been accepted for review by the EMA as PrEP for immunocompromised patients who often do not respond adequately to vaccination alone and remain at high risk of serious outcomes from COVID-19.
There is currently one antibody available for PrEP in COVID-19 – Invivyd’s Pemgarda (pemivibart) – which was granted emergency use authorisation (EUA) in the US in March for adults and adolescents who are moderately-to-severely immunocompromises.
So far, Pemgarda is not available outside the US, and immunocompromised patients currently have no options for COVID-19 protection in Europe beyond vaccination.
AZ said the EMA’s human medicines committee, the CHMP, has granted sipavibart accelerated assessment “as it was deemed of major interest for public health and therapeutic innovation.” The company is also discussing marketing applications with other regulatory authorities.
The filing comes as there are discussions about a possible ‘summer wave’ of COVID-19 in Europe and the US, with a slight increase in the number of people being hospitalised with the disease that seems to be driven by people aged 85 and over. The uptick has coincided with the emergence of a new group of variants of COVID-19, collectively known as FLiRT, that includes strains like JN1, KP2, and KP3.
According to AZ’s INFORM real-world evidence study, immunocompromised people accounted for about 25% of COVID-19 hospitalisations, intensive care admissions and deaths, but only made up around 4% of the overall study population.
“The disease burden of COVID-19 remains high for immunocompromised patients who are disproportionately impacted compared to the general population, despite vaccination,” said Prof Paul Loubet, an infectious diseases specialist at the University of Montpellier in France.
“With cases expected to rise in the winter months, adding more pressure to stretched healthcare systems, sipavibart has the potential to be an important option for immunocompromised patients who remain at risk.”
Prof Loubet was an investigator in AZ’s SUPERNOVA trial of sipavibart, which demonstrated protection from symptomatic COVID-19 with the antibody in a mixed variant environment compared to control.
According to AZ, SUPERNOVA is the only phase 3 trial with efficacy data for COVID-19 PrEP carried out exclusively in immunocompromised patients.
Invivyd said earlier this year it expects Pemgarda to make sales of between $150 million and $200 million in 2024.
https://pharmaphorum.com/news/astrazeneca-files-rival-pemgarda-covid-prep
AstraZeneca's COVID prevention drug application gets EU fast-track assessment
AstraZeneca said on Monday the EU drug regulator has accepted a market authorisation application for its investigational COVID-19 prevention drug, Sipavibart, under an accelerated assessment.
The submission was based on positive data from a late-stage trial that showed the drug helped reduce the incidence of COVID-19 in immunocompromised patients.