FDA Approves LUMAKRAS with VECTIBIX for KRAS G12C-Mutated Colorectal Cancer; PYC Receives FDA Rare Pediatric Disease Designation for VP-001; Novo Nordisk Links High-Dose WEGOVY to Increased Weight Loss; FDA Rejects Atara’s EBVALLO Due to Manufacturing Issues; Boehringer Faces Phase III Schizophrenia Fail and Legal Challenges

FDA Approves LUMAKRAS and VECTIBIX for KRAS G12C-Mutated Colorectal Cancer

Amgen has secured FDA approval for LUMAKRAS (sotorasib) in combination with VECTIBIX (panitumumab) as a treatment for adults with KRAS G12C-mutated metastatic colorectal cancer (mCRC) who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. This approval is underpinned by the Phase III CodeBreaK 300 study, which showcased the combination’s ability to significantly enhance progression-free survival (PFS) compared to existing standards of care. The approval marks a significant step forward in providing targeted therapy for this specific patient population.

The CodeBreaK 300 trial revealed that LUMAKRAS (960 mg daily) plus Vectibix delivered a median PFS of 5.6 months versus 2 months for standard care. Additionally, the combination achieved an overall response rate (ORR) of 26%, while the standard care yielded 0%. Safety profiles were consistent with historical data for both therapies, with common adverse effects including rash, diarrhea, and musculoskeletal pain. This innovative dual-targeted approach addresses a significant unmet need in the treatment of KRAS G12C-mutated mCRC.

“KRAS mutations are historically associated with worse outcomes, and standard treatment options have shown minimal benefit,” said Dr. Marwan G. Fakih, co-director of the Gastrointestinal Cancer Program at City of Hope. “This combination of sotorasib and panitumumab represents a much-needed treatment option, demonstrating superior progression-free survival in clinical trials.” Michael Sapienza, CEO of the Colorectal Cancer Alliance, added, “This breakthrough offers new hope to patients living with metastatic colorectal cancer and emphasizes the importance of innovation in precision medicine.”

FDA Grants PYC Rare Pediatric Disease Designation for VP-001 Drug Program

PYC Therapeutics is making significant strides in precision therapies for genetic diseases with limited or no treatment options. Among its promising assets is VP-001, an investigational drug candidate targeting Retinitis Pigmentosa type 11 (RP11), a rare childhood blinding eye disease caused by PRPF31 mutations. Currently in Phase I/II studies, VP-001 is on track for a potentially registrational trial in 2025, underscoring the company’s commitment to addressing unmet needs in rare genetic disorders.

In a major milestone, VP-001 has been granted Rare Pediatric Disease (RPD) designation by the U.S. Food and Drug Administration (FDA) for PRPF31-associated vision loss. The RPD program is designed to encourage the development of therapies for severe and rare conditions impacting children by offering potential benefits such as priority review vouchers. This designation validates PYC’s innovative approach to tackling diseases like RP11 and paves the way for advancing VP-001 through clinical development.

By focusing on precision therapies, PYC Therapeutics is creating hope for patients with rare genetic diseases, such as RP11, that currently lack effective treatments. With VP-001 advancing steadily, the company is poised to transform the therapeutic landscape for inherited retinal diseases.

Novo Nordisk Links High-Dose WEGOVY to Greater Weight Loss in Phase III Trial

Novo Nordisk has announced positive headline results from STEP UP, a Phase 3b trial within its global STEP program. The 72-week study assessed the efficacy and safety of subcutaneous semaglutide 7.2 mg compared to semaglutide 2.4 mg and placebo, administered weekly alongside lifestyle interventions. The trial involved 1,407 adults with obesity and achieved its primary endpoint, demonstrating statistically significant and superior weight loss with semaglutide 7.2 mg.

Participants receiving semaglutide 7.2 mg achieved an average weight loss of 20.7% from a baseline of 113 kg, compared to 17.5% with semaglutide 2.4 mg and 2.4% with placebo when adherence to treatment was assumed. Additionally, 33.2% of those treated with semaglutide 7.2 mg achieved a weight loss of 25% or more, surpassing the 16.7% seen with semaglutide 2.4 mg and 0% with placebo. The treatment policy estimand analysis showed weight reductions of 18.7%, 15.6%, and 3.9% for semaglutide 7.2 mg, 2.4 mg, and placebo, respectively.

Semaglutide 7.2 mg demonstrated a safe and well-tolerated profile, with gastrointestinal side effects being the most common, primarily mild to moderate and diminishing over time.

“We are very pleased to demonstrate 20.7% weight loss and to see that 33% of patients achieved more than 25% weight loss with semaglutide 7.2 mg, with a safety and tolerability profile comparable to semaglutide 2.4 mg,” said Martin Holst Lange, executive vice president for Development at Novo Nordisk. He highlighted that these results further reinforce semaglutide’s clinical potential, building on the benefits established with Wegovy®, including cardiovascular risk reduction demonstrated in the SELECT trial.

FDA Rejects Atara’s Cell Therapy EBVALLO Due to Manufacturing Issues

Atara Biotherapeutics, Inc. has received a Complete Response Letter (CRL) from the FDA for its Biologics License Application (BLA) for EBVALLO™ (tabelecleucel). This investigational therapy is intended for adult and pediatric patients aged two years and older with Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD) who have undergone at least one prior treatment, including an anti-CD20 therapy.

The CRL pertains to observations made during a routine pre-license inspection of a third-party manufacturing facility. Importantly, no deficiencies were identified in EBVALLO’s manufacturing process, clinical efficacy, or safety data, and the FDA has not requested additional clinical trials. Atara has committed to addressing these observations with its partner, Pierre Fabre Laboratories, and the third-party manufacturer, aiming for a resubmission that could potentially secure approval within six months.

“We are working closely with all stakeholders to address the FDA’s feedback and remain confident in the potential of EBVALLO to meet the significant unmet need for patients with EBV+ PTLD,” said Cokey Nguyen, Ph.D., President and CEO of Atara. The company plans to leverage the recent EMA approval of the FUJIFILM Diosynth Biotechnologies facility in Thousand Oaks, CA, as part of its global manufacturing strategy. 

Approved by the European Commission in December 2022, EBVALLO is an innovative, allogeneic Epstein-Barr virus-specific T-cell immunotherapy designed to eliminate EBV-infected cells. The U.S. BLA submission is based on the pivotal ALLELE study, which demonstrated a 50% Objective Response Rate (ORR) and a favorable safety profile, reinforcing its potential as a first-in-class treatment for patients with this rare and life-threatening condition.

Boehringer Faces Phase III Schizophrenia Fail and Legal Challenges from HHS

Boehringer Ingelheim has announced the discontinuation of its late-stage schizophrenia program following disappointing results from the Phase III CONNEX trials for its investigational drug iclepertin. The trials, designed to evaluate the drug’s ability to improve cognitive and functional outcomes in schizophrenia patients, failed to meet their primary and secondary endpoints. At six months, iclepertin showed no significant improvements compared to placebo in any of the three studies.

As a result, the company has decided to halt the planned long-term extension trial for iclepertin. While this marks a setback for Boehringer’s efforts in schizophrenia, the company remains committed to advancing treatments for mood disorders. Boehringer highlighted its pipeline of over 20 investigational therapies in various stages of development, spanning schizophrenia, major depressive disorder, and other therapeutic areas.

In a separate development, Boehringer continues to face challenges related to its legal dispute over the Inflation Reduction Act (IRA) and its drug price negotiation provisions. The company, alongside other pharmaceutical giants, has argued that the IRA’s provisions amount to unconstitutional property seizure under the Fifth Amendment.

However, a Connecticut court ruled in July 2024 that participation in the IRA’s price negotiations is voluntary, with companies free to opt out if they deem it unprofitable. This week, the Department of Health and Human Services (HHS) reaffirmed this position in a legal filing, emphasizing that the program does not mandate property transfer and allows companies to withdraw from Medicare if they choose.

While Boehringer has faced significant challenges on both clinical and legal fronts, the company continues to focus on its broader research initiatives and its innovative pipeline, aiming to deliver transformative treatments across therapeutic areas.