This story has been updated to clarify that Alecensa was previously approved as a first- and second-line treatment for ALK-positive NSCLC, and that Roche filed for full approval of inavolisib.
NEW YORK – Roche has filed for approval in the US for its PI3Kα inhibitor inavolisib as a first-line treatment for PIK3CA-mutated hormone receptor (HR)-positive breast cancer, Roche CEO Thomas Schinecker said during a call Wednesday to discuss the company's Q1 2024 financial performance.
Roche is expecting the US Food and Drug Administration to issue a regulatory decision on the drug late in 2024. Roche Pharmaceuticals CEO Teresa Graham estimated that, if approved, inavolisib could be a CHF 2 billion ($2.19 billion) market opportunity over time. Inavolisib would also be another option in the PIK3CA-mutated breast cancer market, where Novartis' PI3Kα inhibitor Piqray (alpelisib) is a player. The use of Piqray has been limited by high rates of hyperglycemia, which often results in dose interruptions or discontinuations.
In results from the Phase III INAVO120 trial, Roche subsidiary Genentech reported that inavolisib combined with Pfizer's CDK4/6 inhibitor Ibrance (palbociclib) and fulvestrant increased median progression-free survival by 57 percent compared to a placebo with Ibrance and fulvestrant in patients with PIK3CA-mutant, HR-positive, HER2-negative locally advanced or metastatic breast cancer. There were also trends favoring the inavolisib arm in terms of overall survival, objective response rate, duration of response, and clinical benefit.
The safety analysis showed that 5.6 percent of patients on the inavolisib combination experienced grade 3 or higher hyperglycemia, compared to none of the patients in the placebo arm. The company has not yet reported rates of lower grade hyperglycemia from INAVO120, but a long-term safety analysis from a Phase I/Ib study of inavolisib plus fulvestrant in the same subset of patients showed that 125 out of 193 patients, or 65 percent, experienced any grade of hyperglycemia, and 42 patients, or 22 percent, had grade 3 or higher hyperglycemia.
Roche and other companies developing next-generation mutant PI3Kα inhibitors are hoping that inavolisib's more favorable safety profile, including lower rates of hyperglycemia, will be an advantage in the market against Piqray. Graham said the clinical trial response rates seen with inavolisib are "incredibly impressive" and underscored its "very good" safety profile. She speculated that inavolisib could attract PI3Kα inhibitor-naïve patients whose PIK3CA mutation status is known early through biomarker testing as well as those unable to tolerate Piqray. "As soon as people are looking for [mutant PIK3CA], they will find more of these patients," Graham said.
Roche executives discussed inavolisib's prospects during a call on the firm's financial performance for the three months ended March 31, during which the firm's overall revenue fell 6 percent to CHF 14.40 billion compared to CHF 15.32 billion in Q1 2023. Roche's revenues increased 2 percent over this period at constant exchange rates (CER). Revenue from the Swiss drugmaker's pharmaceuticals division decreased 6 percent to CHF 10.92 billion from CHF 11.61 billion in the year-ago period. In the diagnostics division, revenue also decreased during this period by 6 percent to CHF 3.48 billion from CHF 3.71 billion. Pharmaceuticals and diagnostics revenue both grew 2 percent at CER.
Roche Group CFO Alan Hippe noted in the call that the Swiss franc has strengthened against "basically all the currencies we are dealing with," but that the company's modeling predicts that the currency impact "might look a little bit better" by the end of the year.
Excluding the impact of declining COVID-19 product sales, Roche would have seen a 7 percent increase in revenues at CER. Schinecker noted the company's revenues are "overcompensating" for the COVID-19 effect and a CHF 385 million negative impact from the loss of exclusivity of six products including the HER2-targeted therapy Herceptin (trastuzumab). Roche expects Q1 2024 to be the last quarter in which there is a material negative impact from decreasing sales of COVID-19 products.
Sales of Alecensa (alectinib), a treatment for ALK-positive non-small cell lung cancer, contributed CHF 355 million in Q1 2024, a 4 percent increase at CER from Q1 2023. The ALK inhibitor was approved last week in the US as an adjuvant treatment for ALK-positive NSCLC, adding a valuable early-line indication to its existing approval as a first- and second-line treatment for those with advanced disease.
In an interview on Tuesday, Josina Reddy, Genentech's VP and global head of development for lung cancer, said the company is advocating expanding biomarker testing for all lung cancer patients with earlier-stage disease.
According to the American Cancer Society, more than 238,000 Americans will be diagnosed with lung cancer in 2024. Between 80 percent and 85 percent of those patients will have NSCLC, among whom about 5 percent will be ALK-positive. The National Comprehensive Cancer Network recommends that all lung cancer patients with stage IB to IIIA NSCLC and some of those with stage IIIB be routinely tested for therapeutically targetable alterations in ALK and EGFR and for PD-L1 expression.
Despite these guidelines, surveys have shown that a proportion of lung cancer patients aren't getting guideline-concordant testing. "It's now really imperative that patients receive the appropriate biomarker testing when they're diagnosed with early-stage lung cancer because that way, they and their physician can have a fully informed discussion about what their potential treatment options might be," Reddy said.
Sales of Roche's PD-L1 inhibitor Tecentriq (atezolizumab) were CHF 865 million in Q1 2024, a 1 percent increase at CER compared to Q1 2023. Tecentriq's growth was driven by increased adoption in the adjuvant NSCLC and first-line hepatocellular carcinoma settings. Graham acknowledged that Tecentriq sales will level off in adjuvant NSCLC due to competition from Merck's PD-L1 inhibitor Keytruda (pembrolizumab), which was approved for the same indication in 2023. "We will continue to see growth in other parts of the world that may offset the competitive impact in the US," Graham said. "Adjuvant lung is clearly one of those places where we are seeing that competitive impact."
In Roche's HER2 franchise, Perjeta (pertuzumab) sales were CHF 936 million in Q1 2024, a 3 percent decrease at CER from Q1 2023. Over the same period, sales of Roche's other HER2-targeted drug Kadcyla (trastuzumab emtansine) grew 3 percent at CER to CHF 483 million. The fixed-dose HER2-targeted combination regimen Phesgo (pertuzumab/trastuzumab/hyaluronidase) recorded CHF 388 million in sales in Q1 2024, up 70 percent at CER from the year-ago period.
In its rare disease segment, Graham said, Roche will seek regulatory approval of the Duchenne muscular dystrophy gene therapy Elevidys (delandistrogene moxeparvovec) this year in Europe. "We're looking forward to bringing this highly impactful therapy to EU patients," Graham said, adding that the first patient outside the US patient has already received Elevidys and additional patients are expected to start treatment in coming weeks. Roche and partner Sarepta Therapeutics launched the gene therapy in the US market in Q1 following its FDA approval in June 2023.
In 2024, Roche is expecting group sales to increase in the mid-single-digit range at CER and core earnings per share to grow in line with sales growth, excluding the impact from resolution of tax disputes in 2023.