Lexicon Announces FDA Approval of INPEFA (Sotagliflozin) For Treatment of Heart Failure

Lexicon Pharmaceuticals, Inc. announced that the FDA has approved INPEFATM (sotagliflozin), a once-daily oral tablet, to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors. The broad label includes heart failure patients with any level of left ventricular ejection fraction (LVEF), including preserved and diminished ejection fraction, as well as patients with or without diabetes.

“The approval of INPEFA, along with the breadth of the label, is a major milestone in Lexicon’s path to fulfilling its mission of pioneering medicines that transform patients’ lives,” stated Lexicon CEO Lonnel Coats. “We anticipate that this significant innovation will be commercially available in the United States by the end of June 2023.”

The approval is based on the results of two randomized, double-blind, placebo-controlled Phase III cardiovascular outcomes studies of INPEFA in patients with or at risk of heart failure. SOLOIST-WHF (Worsening Heart Failure) and SCORED enrolled about 12,000 patients together. In individuals who had previously been hospitalized for worsening heart failure, INPEFA dramatically reduced the risk of the composite of hospitalizations for heart failure, urgent visits for heart failure, and cardiovascular mortality by 33% compared to placebo.

Heart failure affects around 6.7 million Americans, with the prevalence anticipated to climb to 8 million by 2030. Heart failure is the primary cause of hospitalization in people 65 and older, accounting for around 1.3 million hospitalizations each year. Patients with heart failure are most likely to have a heart failure event within 30 days of release, with 7% dying and 25% requiring rehospitalization within one month.

“Based on the outcomes observed in the SOLOIST-WHF study, initiating treatment with INPEFA prior to or upon hospital discharge has the potential to reduce the burden of readmissions on patients, carers, providers, and health systems,” said Craig Granowitz, M.D., Ph.D., Lexicon’s senior vice president and chief medical officer. “With today’s FDA approval, INPEFA is now a valuable option for physicians to consider when treating patients who are transitioning out of the hospital and working to break the cycle of repeated hospitalizations.”

Lexicon anticipates that INPEFA will be accessible by the end of June 2023. The company intends to keep the wholesale acquisition cost of the pharmaceutical comparable to that of existing branded heart failure treatments.

PTC Therapeutics Announces Topline Results from Vatiquinone MOVE-FA Registration-Directed Trial

PTC Therapeutics, Inc. announced topline results from the MOVE-FA study of vatiquinone in Friedreich ataxia patients. The primary goal of statistically significant change in mFARS score at 72 weeks was not met in the primary analysis population. The vatiquinone treatment for Friedreich ataxia, on the other hand, demonstrated a significant benefit on major illness subscales and secondary endpoints. Furthermore, significance was achieved in the mFARS endpoint and numerous secondary endpoints in the population of participants who completed the trial protocol.

“While we are disappointed that the study did not achieve its primary endpoint, we are encouraged by the findings of meaningful impact on several different aspects of FA disease progression and morbidity over 72 weeks,” stated Matthew B. Klein, M.D., CEO of PTC Therapeutics. “Given the signals of clinical benefit, vatiquinone’s well-established safety profile in children, and the unmet medical need for paediatric patients with FA, we look forward to discussing a potential path to registration with regulatory authorities.”

The MOVE-FA trial included 146 pediatric and adult patients, the vast majority of whom were under the age of 18. In the primary analysis population, the mean placebo-corrected change in mFARS score was 1.6 (p=0.14). Notably, there was a substantial improvement in the bulbar and upright stability subscales (nominal p values of 0.044 and 0.021, respectively), which are thought to be representative of major features of disease morbidity and prognostic of time to loss of ambulation. Furthermore, a statistically significant change on the Modified Fatigue Scale, which reflects one of the most important sources of disease morbidity (nominal p-value of 0.025), was seen. The placebo corrected difference was 2.31 in a prespecified sensitivity analysis of participants who completed 72 weeks on assigned medication, representing a 75% slowdown in disease development over 72 weeks. Overall, vatiquinone was well tolerated, contributing to the huge body of safety data gathered in earlier pediatric clinical studies.

EMA Recommends Revoking EU Approval For Novartis’s Sickle Cell Disease Drug

The European Medicines Agency committee has recommended the withdrawal of the marketing authorization for Novartis’ Adakveo, a medication used to prevent vaso-occlusive crises, which are painful episodes experienced by individuals aged 16 years and older with sickle cell disease (SCD).

Adakveo, also known as crizanlizumab, received conditional approval in the European Union in October 2020. The Committee for Medicinal Products for Human Use (CHMP) of the EMA stated that their opinion, announced on Friday, was based on a thorough evaluation conducted by the committee, which determined that the risks of the drug outweighed its benefits.

The evaluation specifically examined the findings of a phase 3 clinical trial called STAND. The trial results demonstrated that Adakveo did not effectively reduce the number of painful crises leading to healthcare visits. Over the course of the first year of therapy, patients treated with Adakveo experienced an average of 2.5 painful crises with subsequent healthcare visits, compared to 2.3 crises in the placebo group, according to the agency’s report.

The Committee for Medicinal Products for Human Use (CHMP) considered additional data from various sources, including other studies, a managed access program, and real-world data. However, these studies had limitations such as the absence of a comparison group, preventing them from demonstrating the effectiveness of Adakveo or counterbalancing the negative outcomes of the STAND study.

Furthermore, the CHMP highlighted that the STAND study did not raise new concerns but did reveal a higher occurrence of severe side effects associated with Adakveo compared to the placebo.

The European Medicines Agency (EMA) had initially required the completion of the STAND study as a condition for granting marketing authorization to Adakveo. This requirement stemmed from the limited data available at the time of conditional approval, which created uncertainty regarding the magnitude of the medication’s effects.

Considering that the data from the STAND study failed to confirm the previously observed benefits of Adakveo, the CHMP concluded that the risks outweigh the benefits and recommended the revocation of the drug’s authorization in the European Union (EU). Subsequently, the European Commission (EC) will issue a legally binding decision based on the CHMP’s recommendation. 

EMA Recommends Approval of Neoadjuvant Nivolumab/Chemotherapy in Resectable NSCLC

Bristol Myers Squibb has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of Opdivo (nivolumab) in combination with platinum-based chemotherapy for the neoadjuvant treatment of resectable non-small cell lung cancer (NSCLC) in adult patients with tumor cell PD-L1 expression of at least 1%, who are at high risk of recurrence. The recommendation will now undergo review by the European Commission, which has the authority to approve medicines for the European Union.

Abderrahim Oukessou, M.D., Vice President and Thoracic Cancers Development Lead at Bristol Myers Squibb, expressed the need for improved treatment options in lung cancer, stating that despite advancements, many patients still face relapse and potential mortality. Oukessou emphasized the significance of the CheckMate -816 trial results, as Opdivo in combination with chemotherapy has shown the ability to reduce the risk of disease recurrence, progression, and death in resectable NSCLC when administered prior to surgery. The CHMP’s recommendation represents a step forward in addressing the urgent need to provide certain patients in the European Union with an effective and well-tolerated pre-surgical option that may lower the risk of relapse.

The positive opinion is based on data from the CheckMate -816 trial, which demonstrated a statistically significant and clinically meaningful improvement in event-free survival (EFS) and pathologic complete response (pCR) when three cycles of Opdivo were administered alongside chemotherapy compared to chemotherapy alone prior to surgery. The safety profile of Opdivo in combination with chemotherapy aligns with previous studies conducted in NSCLC. Key findings on pCR, EFS, and preliminary overall survival (OS) data from CheckMate -816 were previously presented at medical conferences and published in the New England Journal of Medicine. Three-year data highlighting the long-lasting clinical benefits of the combination therapy were recently presented at the European Lung Cancer Congress 2023. CheckMate -816 is an ongoing trial that continues to assess important secondary endpoints and subgroup analyses, including OS, as the data continue to mature.

Opdivo in combination with chemotherapy has received approval for neoadjuvant treatment in patients with resectable non-small cell lung cancer (NSCLC) in 21 countries, including the United States, Japan, and China. The approval is irrespective of PD-L1 expression levels. Regulatory authorities worldwide are currently reviewing additional applications for Opdivo-based treatments. Opdivo has demonstrated improved effectiveness in neoadjuvant or adjuvant therapy for four types of tumors, namely lung cancer, bladder cancer, esophageal/gastroesophageal junction cancer, and melanoma.

FDA Grants Priority Review to Fruquintinib for Previously Treated mCRC

On May 25, 2023, Takeda (TSE:4502/NYSE:TAK) and HUTCHMED (China) Limited (Nasdaq/AIM:HCM, HKEX:13) (HUTCHMED) announced that the US FDA has granted priority review of the New Drug Application (NDA) for fruquintinib, a highly selective and potent inhibitor of vascular endothelial growth factor receptors (VEGFR) -1, -2 and -3 for the treatment of adult patients with previously treated metastatic colorectal cancer (CRC). Fruquintinib was designed to improve kinase selectivity with the intention of minimizing off-target toxicities, improving tolerability, and providing more consistent target coverage. If authorized, fruquintinib will be the first and only highly selective inhibitor of each of the three VEGF receptors authorized in the United States for metastatic CRC that has already received treatment. As per the update from Takeda, the FDA set November 30, 2023, as the Prescription Drug User Fee Act (PDUFA) goal date for this NDA.

“We are confident that fruquintinib has the potential to transform the treatment landscape for those living with previously treated metastatic colorectal cancer, as demonstrated by its strong clinical profile. There are significant needs for patients with this disease in the U.S., and we believe fruquintinib has the potential to address these needs regardless of patients’ biomarker status. We look forward to continuing conversations with the FDA with the goal to make this therapy available to patients as soon as possible.”

Awny Farajallah, M.D., head of Global Medical Affairs Oncology at Takeda

“The clinical benefit of fruquintinib has been confirmed in multiple ways, from global clinical studies to commercialization in China. We are pleased to have Takeda as our partner, furthering development and commercialization of fruquintinib outside of China. Today’s acceptance marks a significant advancement towards the goal of providing patients with previously treated metastatic colorectal cancer a much-needed therapeutic option, given the limited treatment options currently available to patients. This also supports our ongoing vision to design and develop differentiated molecules that help patients with high unmet needs globally.”

Dr. Michael Shi, Head of R&D and Chief Medical Officer, HUTCHMED

The NDA for fruquintinib includes results from the Phase 3 FRESCO-2 trial, along with data from the Phase 3 FRESCO trial conducted in China. FRESCO-2 is a global Phase 3 multi-regional clinical trial (MRCT) conducted in the U.S., Europe, Japan, and Australia investigating fruquintinib plus best supportive care (BSC) vs placebo plus BSC in patients with previously treated metastatic CRC. The FRESCO-2 trial met its primary and key secondary endpoints, showing a significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS). Fruquintinib has been generally well tolerated in patients to date.

In China, frucintinib is currently approved under the brand name ELUNATE®. The therapy is approved in China, based on the FRESCO study, a Phase 3 pivotal registration trial of fruquintinib in 416 patients with metastatic CRC. The study’s findings were published in The Journal of the American Medical Association, JAMA, in June 2018 (NCT02314819). HUTCHMED and Takeda finalized an exclusive licensing deal in March 2023 to further the development, marketing, and production of fruquintinib outside of China.

Vega Therapeutics Receives FDA Orphan Drug Designation for VGA039 for the Treatment of von Willebrand Disease

On May 23, 2023, Vega Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted the company orphan drug designation for VGA039 for the treatment of von Willebrand disease (VWD).

VGA039 is a first-in-class antibody treatment that regulates Protein S, a crucial co-factor involved in thrombin production during both the initiation and propagation phases of coagulation. As a subcutaneously self-administered antibody therapy, VGA039 has the potential to revolutionize the management of VWD by addressing a key mechanism of clot formation in VWD and increasing thrombin production by targeting Protein S.

“Receiving orphan drug designation status is an important step for VGA039. VGA039 has the potential to be a new treatment for VWD with a profile to reduce the treatment burden for people living with this disease.” 

Gary Patou, MD, Chief Medical Officer of Vega Therapeutics.

A phase 1 clinical trial is now being conducted to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic profile of VGA039 across sites in the EU and the US. VGA039 has shown efficacy in preclinical tests for VWD and many other congenital bleeding diseases.

Von Willebrand disease (VWD) is a bleeding ailment that causes the blood to not clot appropriately. Von Willebrand disease is the most common inherited bleeding disorder in the United States, affecting as many as 1 in every 1000 individuals. Von Willebrand disease is often compared to hemophilia, but it is a different condition and has a different pattern of bleeding. It affects both boys and girls equally (while hemophilia mainly affects boys). A parent with VWD has a 50% chance of passing the gene to his or her child. Severe bleeding due to Von Willebrand disease can harm organs and have a big impact on the patient’s daily life. Only a few treatments are available right now, and they all involve repeated intravenous (IV) infusions of factor replacement therapy. Apart from Vega Therapeutics, there are several other major pharma and biotech companies evaluating their drug candidate for the treatment of Von Willebrand disease. The ongoing clinical trials hold immense potential to transform the Von Willebrand disease treatment outlook in the coming years.