NEW YORK – On the second day of the 39th annual JP Morgan Healthcare Conference, Eli Lilly and Pfizer discussed the potential of their competing CDK4/6 inhibitors; GSK highlighted a trial comparing bintrafusp alfa against pembrolizumab (Merck’s Keytruda) in PD-L1-high, advanced non-small cell lung cancer; and Clovis Oncology detailed plans to expand its PARP inhibitor rucaparib (Rubraca) into new biomarker-guided indications. Below are brief reports on the presentations covered by our team.
Coverage of the first day of the conference can be found here.
Eli Lilly Chairman and CEO David Ricks said that he hopes that the company's CDK4/6 inhibitor abemaciclib (Verzenio) will soon garner the US Food and Drug Administration's approval in the adjuvant setting for high-risk, early-stage, hormone receptor (HR)-positive, HER2-negative breast cancer patients. The drug, which is already approved for advanced or metastatic breast cancer, demonstrated an invasive disease-free survival benefit in the adjuvant setting in combination with endocrine therapy in the MonarchE trial compared to just endocrine therapy, though some argued that the two-year follow-up period was not long enough to confirm the agent's benefit.
Ricks is of the view that the MonarchE data, as they stand, are "more than sufficient" to warrant abemaciclib's approval in the adjuvant setting, and wagered, "I'm sure some experts are even using the drug [in this setting] now off-label."
He reminded investors that by the time abemaciclib garners approval, should that occur, there will be data from longer follow-up, further supporting the drug's adoption. "Once approved, we expect a very strong uptake in that setting," he said, adding that it would likely be a long time before the data could be replicated by a competing drug, positioning adjuvant abemaciclib as a "great opportunity" for Eli Lilly.
Like Eli Lilly, Pfizer also was hoping to advance its CDK 4/6 inhibitor palbociclib (Ibrance) into the adjuvant, hormone receptor (HR)-positive, HER2-negative breast cancer setting. However, longer follow-up in the PENELOPE-B study showed that one year of palbociclib added to at least five years of endocrine therapy did not improve invasive disease-free survival compared to five years of just endocrine therapy.
Palbociclib is currently approved for HR-positive, HER2-negative advanced or metastatic breast cancer patients in combination with an aromatase inhibitor or with fulvestrant in progressing patients. In the third quarter, palbociclib's worldwide sales were $1.4 billion, up 6 percent compared to $1.3 billion from Q3 2019. In comparison, Lilly's abemaciclib (Verzenio) had worldwide sales of $234.4 million in Q3 2020, a 49 percent increase from $157.2 million in Q3 2019.
At the conference, Pfizer CEO Albert Bourla said palbociclib still holds the dominant position within the CDK inhibitor class, accounting for 86 percent of the total scripts. "In terms of maintaining our [position] within the CDK [inhibitor] class, I feel quite comfortable," he said, noting that there is much room for driving palbociclib's adoption among metastatic breast cancer patients who are getting chemotherapy or single-agent targeted treatments.
Despite the potential threat of Lilly's abemaciclib likely moving into the adjuvant setting, Bourla maintained that Pfizer will be able to hold on to the top position in the class. "I feel very comfortable now, not only because we keep doing market research and we're examining what the preference of physicians would be now that they have data from the competition in the adjuvant [setting], but also I see how scripts are moving," he said. "In metastatic breast cancer, we will remain stable for our market share and collectively we will grow the CDK [inhibitor] market."
Pfizer previously projected at least a 6 percent five-year compound annual growth rate on an adjusted basis, not including COVID-19 vaccine sales. Bourla also said he is "very confident" Pfizer will be able to deliver on that.
GlaxoSmithKline's Chief Scientific Officer Hal Barron discussed the potential of bintrafusp alfa, a bifunctional fusion protein immunotherapy that it is co-developing with Merck KGaA. "This asset could have very large implications for patients, and commercially, if it was to work," he said.
The drug is being explored in a number of trials involving patients with lung, triple-negative breast, and biliary cancers, where researchers are exploring bintrafusp's activity in various biomarker-defined settings. For example, in non-small cell lung cancer, a Phase III study is comparing bintrafusp against pembrolizumab (Merck's Keytruda) in patients with advanced tumors characterized by high PD-L1 expression. Barron said that if this trial shows bintrafusp is better than pembrolizumab in this highly competitive setting, then it would be a "game changer."
In a separate presentation at the conference, Merck KGaA CEO Stefan Oschmann also highlighted bintrafusp's potential and noted that a study in second-line advanced or metastatic biliary cancer is slated to read out this year. In that study researchers also are looking at objective response rates and durable responses based on patients' PD-L1 expression and microsatellite instability (MSI) status.
GSK, however, appears interested in advancing its PD-1 inhibitor dostarlimab in combination with carboplatin-paclitaxel in an all-comer advanced or recurrent endometrial cancer population in the Phase III RUBY trial, though patients must have sufficient tissue at screening for MSI testing. GSK considered the impact of MSI status on dostarlimab response in the earlier multi-cohort, Phase I/II GARNET trial, in which dostarlimab monotherapy resulted in durable responses in recurrent or advanced endometrial cancer patients after a platinum-based regimen, regardless of their MSI status. The company presented updated results from GARNET on the mismatch repair-deficient population last year, where dostarlimab also showed activity. The company is expecting the PD-1 inhibitor to be approved in second-line endometrial cancer this year, Barron said.
The firm also has a strong focus on advancing drugs that interrogate synthetic lethality and inked a deal with Ideaya last year toward that end. GSK is particularly interested in seeing if combining its PARP inhibitor niraparib (Zejula) with dostarlimab can fire up the immune system against "cold tumors," such as ovarian cancer, that usually don't respond well to immunotherapy. In the Phase II MOONSTONE trial, for example, researchers are investigating niraparib-dostarlimab in advanced or relapsed ovarian cancer patients who don't have a BRCA1/2 mutation. Barron suggested that the populations most-likely to benefit from such combinations need to be identified, and as such the development programs may be more complicated.
Clovis Oncology CEO Patrick Mahaffy said that to date his company has been largely perceived as a specialty pharma with "modest sales growth," an image the company is working to shed. Over this and next year, he expects Clovis will show itself as a biotech with growing revenues due to its expanding pipeline of precision oncology products and the increasing adoption of the PARP inhibitor rucaparib (Rubraca).
Rucaparib is already approved in the US and in Europe as a second-line maintenance treatment for platinum-responsive ovarian cancer patients and for those with a BRCA1/2 mutation after receiving at least two chemotherapies. Last year, the US Food and Drug Administration also approved rucaparib for BRCA1/2-mutated, metastatic castration-resistant prostate cancer patients previously treated with an androgen receptor-directed treatment or taxane-based chemo.
Earlier this week, Clovis estimated global sales for rucaparib of between $43.0 million and $43.5 million in the fourth quarter in 2020 compared to $39.3 million in Q4 in 2019. The drug’s sales for the full year are expected to be between $164.2 million and $164.7 million in 2020 compared to $143.0 million in 2019. Mahaffy noted that revenues were particularly encouraging in European markets, despite the COVID-19 pandemic. Clovis expects to end the year with $240 million in cash and cash equivalents as of Dec. 31, which will fund the company's operating plans into 2023.
Although PARP inhibitors are a mainstay of treatment for ovarian, prostate, and other cancers, the main question is whether they will have broad activity or be restricted to molecularly defined subpopulations, Mahaffy noted. Toward that end, Clovis is working to gain market share in the second-line ovarian cancer maintenance therapy setting, where rucaparib is available to patients regardless of their BRCA1/2 mutation status.
While the growth in revenues for rucaparib based on currently approved indications is encouraging, "the bigger driver of growth is going to be new indications," said Mahaffy.
In the potentially registration-enabling LODESTAR trial, Clovis is eyeing a tumor-agnostic indication for rucaparib in patients with solid tumors characterized by homologous recombination repair (HRR) gene mutations. The company may make a regulatory submission based on data from this trial in the second half of this year or first half of 2022. The TRITON3 trial, looking at rucaparib against physicians' choice of therapy (abiraterone acetate, enzalutamide, or docetaxel) in metastatic castration-resistant prostate cancer with HRR deficiency, is currently enrolling patients.
Mahaffy also highlighted the anticipated readout from the Phase III ATHENA trial, investigating rucaparib alone and in combination with nivolumab (Bristol Myers Squibb's Opdivo) in ovarian cancer patients after front-line maintenance platinum chemotherapy. In this 1,000-patient trial, treatment response also will be evaluated based on HRR status. The rucaparib monotherapy arm may read out later this year, leading to a potential label expansion in this setting in 2022, while the rucaparib-nivolumab combination is slated to read out next year.
Invitae CEO Sean George said that although the last month and a half has been one of the strongest for the molecular diagnostics company, more recently, counties the firm operates in have instituted restrictive measures due to the growing number of COVID-19 infections. "We have a production facility in Southern California, and frankly, the last couple of weeks were a bit of a mess down there," George said.
Ahead of its presentation at the conference, Invitae said that it expects its 2020 revenues to increase by 28 percent from the prior year to $278 million, but the company's $450 million revenue projection for 2021 fell well below the consensus Wall Street expectation of $513.7 million.
Despite the promising momentum, "we're acutely aware there is a fair amount of uncertainty left," George said, adding that it is "hard to say how that's going to play out this year." Despite the conservative short-term outlook, over the next two to three years, Invitae will be able to achieve 50 percent to 60 percent revenue growth, he predicted.
Jason Myers, Invitae's president of oncology, said that following completion of the ArcherDX acquisition, Invitae reached one of its milestones in November by submitting a premarket approval application for the Stratafide next-generation sequencing test for personalizing cancer treatments. The company is seeking the US Food and Drug Administration's approval for the tissue- and blood-based test kit as a class II device with de novo claims and as a class III device with companion diagnostic claims. The FDA will likely take between 90 and 180 days to review the test as a class II device, though it may take longer, between 180 and 270 days, to review the higher-risk CDx claims, some of which are linked to drugs with breakthrough therapy status.
Invitae has discussed the proposed indications for Stratafide with the Centers for Medicare & Medicaid Services, and Myers said that if the FDA approves the test's CDx claims, it will be eligible for national Medicare coverage. He noted that the specific price point at which the test will be reimbursed still needs to be ironed out with payors.
Meanwhile, the company's Personalized Cancer Monitoring test for measuring minimal residual disease (MRD) will be integrated within Invitae's "core production engine," making it a resource not just for pharmaceutical companies developing immunotherapies but "customers of all sorts," Myers said. Although the MRD space is becoming highly competitive, with Guardant Health and Grail both announcing plans to advance tests this week, George isn't bothered about Invitae's ability to compete.
"We've been in a pretty rough and tumble environment" in the hereditary cancer genetic testing space, where there are numerous competitors, he reflected. "We've been competing in a sharp-elbowed space for a while." With 44 million new cancer diagnoses annually, George expects competition to increase in the near term. However, the competitors will fall away over the longer term, he said, as customers look for a one-stop solution that can serve cancer patients' testing needs throughout their disease trajectory, which he added is what Invitae is trying to build.
On Wednesday, a day after its JPM presentation, Invitae said that it is collaborating with Pacific Biosciences to develop a production-scale, high-throughput, whole-genome sequencing platform for clinical use.
Sema4 CEO Eric Schadt revealed in his conference presentation on Tuesday that the firm generated revenue of approximately $190 million in 2020. He said the firm expects revenues to grow at a compound annual growth rate of 38 percent through 2023, when it projects revenues of $504 million.
The Stamford, Connecticut-based company projects its oncology solutions business to grow 240 percent year over year, Schadt said, but did not disclose revenues or test volumes.
"Today a lot of revenues are generated around genomic testing," Schadt said, "but increasingly they'll be generated through secondary insights," including novel disease models that can inform clinical care, reduce cost, and improve outcomes, as well as tools and technologies that improve clinical trial efficiency and accelerate drug discovery.
Revenue from partnerships accounted for 4 percent of total revenues in 2020, but Sema4 projects that to grow to 30 percent by 2023.
Schadt also noted that Sema4, a Mount Sinai Medical System spinout combining genomic testing with other clinical data analysis, has partnered with GlaxoSmithKline to generate predictive analytical insights into the diagnosis and progression of cancer patients. Under that alliance, Sema4 is performing whole-exome and whole-transcriptome profiling of hundreds of breast and ovarian cancer samples provided by GSK and generating "molecular-level data that can be combined with existing real-world data and imaging data to provide a comprehensive view of data associated with certain cancer types," according to Schadt.
In its oncology business, CEO Steve Chapman said the company is mostly focusing on minimal residual disease testing, a $15 billion market opportunity. It has published results for its Signatera test in colorectal, breast, lung, bladder, and other cancer types and has "seen consistently very high levels of performance" of 88 to 100 percent sensitivity in detecting relapse ahead of imaging, and greater than 98 percent positive predictive value, he said.
Natera's pharmaceutical business for Signatera also grew significantly last year, he said. The company signed contracts valued at more than $65 million in 2020, he noted, including for multiple Phase III clinical trials, and the average deal size is getting larger.
Chapman pointed specifically to a bladder cancer study sponsored by Genentech that showed that using MRD testing as a selection criterion for treatment had a significant survival benefit. "We think this is now a must for all pharma companies, to include MRD assessment in every adjuvant trial," he said.
In clinical testing, Natera is going after colorectal cancer as the first indication for Signatera, an opportunity of about 1 million tests annually for stage II and III CRC alone. In that setting, the test can be used for adjuvant decision-making as well as for surveillance, he said. Its second indication, to be launched later this quarter, is for monitoring response to immuno-oncology therapies, where the test is "outperforming the tissue-naïve products that are on the market," he said. Natera hopes to get Medicare reimbursement in this setting this summer, when a local coverage decision is finalized.
Looking to other cancer types, Natera has published clinical studies in lung, bladder, breast, and esophageal cancer already, he said, and more than 50 additional studies are ongoing. "This is going to allow us to unlock many other different cancer types under the umbrella LCD coverage," he said.
Regarding its 2019 deal with Foundation Medicine to develop personalized cancer monitoring assays, Chapman said that the partners have made "a lot of progress" and expect to launch assays for biopharmaceutical customers this year, followed by a clinical launch.
The company also has completed work with BGI to get its Signatera test up and running in China, he said, and has signed a handful of agreements with pharmaceutical studies that have an arm in China. Following these pharma studies, Natera will "focus on the clinical opportunity where we're working hand in hand with BGI to work out the launch strategy," he said.
In the near term, the firm sees a market opportunity of 1 million Signatera tests per year for colorectal cancer, 800,000 tests for cancer immunotherapy response monitoring, and 600,000 tests for new cancer indications. "Ultimately, we think this will be a pan-cancer assay," he said, adding that more updates will come during Natera's next earnings call.