Novartis Pharmaceuticals Corp.

iStock, lakshmiprasad S The Big Pharma companies made a last-ditch effort asking a U.S. appeals court to reconsider their lawsuits against the Inflation Reduction Act’s Medicare drug price negotiations, which they contend infringe on their constitutional rights. AstraZeneca , Bristol Myers Squibb and Johnson & Johnson last week appeared before a U.S. Court of Appeals for the Third Circuit panel of judges in a bid to revive their legal challenge to the Inflation Reduction Act’s Drug Price Negotiation Program, according to media reports. Lawyers for the companies took aim at the constitutionality of the Medicare program, insisting that the drug negotiations violate several of the companies’ core constitutional rights. According to the court minutes , each pharma was given 20 minutes to lay out its arguments before the panel, focusing on one constitutional issue. The U.S. government’s lawyers were also allotted 20 minutes to provide the counterpoints to the legal claims. Jones Day lawyer Yaakov Roth in an argument for BMS claimed that the drug price negotiations do not give the pharma companies an opportunity to negotiate. Instead, the program is akin to a “gun to the head” since non-participation is met with either steep fines or losing access to the Medicare market, according to Reuters . Roth argued that the Inflation Reduction Act (IRA) Drug Price Negotiation Program violates the companies’ Fifth Amendment right to due process and against the unlawful seizure of property by the government without proper compensation. Covington & Burling’s Kevin King, representing J&J subsidiary Janssen Pharmaceuticals, focused on the First Amendment and arguing that the term “maximum fair price”—which the negotiation program uses to refer to the final agreed-upon drug prices—is misleading. The label implies that the companies have agreed the new pricing is fair, even if that isn’t the case. Government lawyer Catherine Padhi countered the industry’s arguments, insisting that the negotiations are voluntary and that the government is free to leverage its purchasing power to secure the best deals it can for Medicare beneficiaries. Padhi maintained that “maximum fair price” is a “statutory term of art”—wording that carries specific legal meaning and “does not reflect a subjective value judgment.” Besides, as King conceded after being questioned by Judge Arianna Freeman, companies are not precluded from putting out their own statements to announce that the IRA prices are not fair, according to Endpoints News . It is yet clear where the appeals judges lean and whether the legal complaints will be taken forward. While the panel sometimes pushed back on the government’s line of argument, pointing out that it may be taking advantage of the huge Medicare market to essentially force companies to comply, the judges noted that industry simply wants the unencumbered benefits of the government’s business and free market pricing. Wednesday’s appeals hearing is the latest development in the industry’s unsuccessful attempt to block the IRA. Last month, a New Jersey district court threw out Novartis’ legal challenge, which made similar constitutional arguments as those by BMS, J&J and AstraZeneca. In August 2024, an Ohio judge similarly dismissed the U.S. Chamber of Commerce’s lawsuit, arguing that the association does not have standing to bring the case against the government. However, in September, the Pharmaceutical Research and Manufacturers of America (PhRMA) scored a rare win as the Fifth Circuit Court of Appeals ⁠ruled⁠ in the trade group’s favor, sending its complaint against the IRA back to a lower Texas court.

On September 17, 2024, the Food and Drug Administration approved ribociclib (Kisqali, Novartis Pharmaceuticals Corporation) with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence. Additionally, FDA also approved the ribociclib and letrozole co-pack (Kisqali Femara Co-Pack, Novartis Pharmaceuticals Corporation) for the same indication. Full prescribing information for Kisqali and Kisqali Femara Co-Pack will be posted on Drugs@FDA. Efficacy and Safety Efficacy of ribociclib with a non-steroidal aromatase inhibitor (NSAI) was evaluated in NATALEE (NCT03701334), a randomized, open-label, multicenter trial in 5101 adults with HR-positive, HER2-negative early breast cancer. The trial included patients with any lymph node involvement (excluding microscopic nodal involvement), or if there was no nodal involvement, either tumor size > 5 cm, or tumor size 2 to 5 cm with either Grade 2 (and high genomic risk or Ki67 ≥ 20%) or Grade 3. Participants were randomized (1:1) to receive ribociclib (400 mg) + NSAI or NSAI alone; patients could receive goserelin as indicated. Randomization was stratified by anatomic stage, prior chemotherapy (neoadjuvant versus adjuvant), menopausal status (premenopausal and males versus postmenopausal) and region (North America/Western Europe/Oceania versus rest of the world). The main efficacy outcome measure was invasive disease-free survival (iDFS). iDFS was defined as randomization to the first occurrence of the following: local or regional invasive breast recurrence, distant recurrence, death from any cause, contralateral invasive breast cancer, or secondary primary non-breast invasive cancer (excluding basal and squamous cell carcinomas of the skin). A statistically significant improvement in iDFS was observed in the intent-to-treat patient population at an interim analysis. Efficacy results at the final iDFS analysis showed that iDFS at 36 months was 90.7% (95% CI: 89.3, 91.8) in the ribociclib + NSAI arm and 87.6% (95% CI: 86.1, 88.9) in the NSAI arm, with a hazard ratio of 0.749 (95% CI: 0.628, 0.892). At the time of the iDFS final analysis, OS was immature. The adverse reactions observed on the NATALEE trial were consistent with the current safety profile for ribociclib in combination with an NSAI. The prescribing information provides additional safety information.  In the adjuvant treatment setting, the recommended ribociclib dose is 400 mg (two 200 mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles. Refer to the prescribing information for the recommended dosage of the aromatase inhibitor.  Kisqali has newly updated storage conditions. Kisqali should now be refrigerated until dispensed to patients. After dispensing, healthcare providers should advise patients to store Kisqali at room temperature for up to 2 months. Expedited Programs This review used the Assessment Aid, a voluntary submission from the Applicant to facilitate the FDA’s assessment.  Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. Follow the Oncology Center of Excellence on X: @FDAOncology.

On September 17, 2024, the Food and Drug Administration approved ribociclib (Kisqali, Novartis Pharmaceuticals Corporation) with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence. Additionally, FDA also approved the ribociclib and letrozole co-pack (Kisqali Femara Co-Pack, Novartis Pharmaceuticals Corporation) for the same indication. Full prescribing information for Kisqali and Kisqali Femara Co-Pack will be posted on Drugs@FDA. Efficacy of ribociclib with a non-steroidal aromatase inhibitor (NSAI) was evaluated in NATALEE (NCT03701334), a randomized, open-label, multicenter trial in 5101 adults with HR-positive, HER2-negative early breast cancer. The trial included patients with any lymph node involvement (excluding microscopic nodal involvement), or if there was no nodal involvement, either tumor size > 5 cm, or tumor size 2 to 5 cm with either Grade 2 (and high genomic risk or Ki67 ≥ 20%) or Grade 3. Participants were randomized (1:1) to receive ribociclib (400 mg) + NSAI or NSAI alone; patients could receive goserelin as indicated. Randomization was stratified by anatomic stage, prior chemotherapy (neoadjuvant versus adjuvant), menopausal status (premenopausal and males versus postmenopausal) and region (North America/Western Europe/Oceania versus rest of the world). The main efficacy outcome measure was invasive disease-free survival (iDFS). iDFS was defined as randomization to the first occurrence of the following: local or regional invasive breast recurrence, distant recurrence, death from any cause, contralateral invasive breast cancer, or secondary primary non-breast invasive cancer (excluding basal and squamous cell carcinomas of the skin). A statistically significant improvement in iDFS was observed in the intent-to-treat patient population at an interim analysis. Efficacy results at the final iDFS analysis showed that iDFS at 36 months was 90.7% (95% CI: 89.3, 91.8) in the ribociclib + NSAI arm and 87.6% (95% CI: 86.1, 88.9) in the NSAI arm, with a hazard ratio of 0.749 (95% CI: 0.628, 0.892). At the time of the iDFS final analysis, OS was immature. The adverse reactions observed on the NATALEE trial were consistent with the current safety profile for ribociclib in combination with an NSAI. The prescribing information provides additional safety information. In the adjuvant treatment setting, the recommended ribociclib dose is 400 mg (two 200 mg film-coated tablets) taken orally, once daily for 21 consecutive days followed by 7 days off in 28-day treatment cycles. Refer to the prescribing information for the recommended dosage of the aromatase inhibitor. Kisqali has newly updated storage conditions. Kisqali should now be refrigerated until dispensed to patients. After dispensing, healthcare providers should advise patients to store Kisqali at room temperature for up to 2 months. This review used the Assessment Aid, a voluntary submission from the Applicant to facilitate the FDA’s assessment. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. Follow the Oncology Center of Excellence on X: @FDAOncologyExternal Link Disclaimer. Content current as of: 09/17/2024 Regulated Product(s) Drugs 09/17/2024 Drugs Resources for Information | Approved Drugs Oncology (Cancer)/Hematologic Malignancies Approval Notifications Ongoing | Cancer Accelerated Approvals Verified Clinical Benefit | Cancer Accelerated Approvals Withdrawn | Cancer Accelerated Approvals Other | Cancer Accelerated Approvals Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description Oncology (Cancer)/Hematologic Malignancies Approval Notifications Ongoing | Cancer Accelerated Approvals Verified Clinical Benefit | Cancer Accelerated Approvals Withdrawn | Cancer Accelerated Approvals Other | Cancer Accelerated Approvals Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description