GSK’s RSV Vaccine Clears Phase III Test in Adults; Roche’s Tecentriq for Adjuvant NSCLC; Owkin Bags $ 180 million from BMS; EU Approves Roche’s Mosunetuzumab; Dostarlimab Elicits Clinical Complete Response in dMMR Rectal Cancer; FDA Backs Bluebird’s CALD Gene Therapy; Takeda’s Dengue Fever Vaccine TAK-003; FDA Approves Dupilumab

GSK Starts Preparations for Regulatory Filings as RSV Vaccine Clears Phase III Test in Adults

GSK plans to initiate preparation for regulatory submissions for its respiratory syncytial virus (RSV) vaccine after the vaccine performed well in the much-anticipated AReSVi 006 trial in individuals aged 60 and above. 

 According to the company, the RSVPreF3 OA vaccine demonstrated “statistically substantial and clinically important” efficacy in this scenario, with consistent action across RSV A and B strains and in older age groups, including those aged >70. The findings are comparable with in-house findings from a parallel Phase III trial (AReSVi 004), which discovered that RSV-directed antibodies persist for at least 6 months after immunization. GSK now hopes to begin regulatory filings for the vaccine in the second half of 2022, intending to bring it to market ahead of rival jabs from Pfizer, Johnson & Johnson, Bavarian Nordic, and Moderna. 

The pharma group also claims that there were no safety concerns with RSVPreF3 OA in the trial, which is significant given that the company was forced to pause injection trials in pregnant moms earlier this year while it evaluated a possible safety risk. However, the adult population represents a significantly larger market for a prospective RSV vaccine, accounting for the majority of GSK’s predicted USD 4 billion in peak sales for its jab. GSK must move swiftly to stay on top of its competitors, particularly Pfizer, which will release the results of its vaccine’s Phase III RENOIR study very shortly.

Meanwhile, J&J began its Phase III EVERGREEN study in September, with results expected in 2023, while Bavarian Nordic and Moderna candidates have also entered the last stage of clinical testing. Furthermore, Moderna has stated that it expects to proceed with a proposal to combine flu, COVID-19, and RSV into a single shot, potentially disrupting the first generation of RVS-only vaccines market.

Roche’s Tecentriq Extends Lead Over Keytruda in Adjuvant NSCLC Domain

While Merck & Co’s Keytruda is the clear leader in the non-small cell lung cancer (NSCLC) category, there is one category where it falls short of Roche’s Tecentriq – treatment of early-stage cases curable with surgery. Roche gained FDA clearance for Tecentriq (atezolizumab) as an adjuvant for certain NSCLC patients last year and has now received European Commission approval for this indication, solidifying its position. Tecentriq has been approved for use after surgery and platinum-based chemotherapy for NSCLC – in patients with tumors expressing 1% or more of the PD-L1 biomarker – to try to prevent the disease from reoccurring.

The EU approval is based on the findings of the IMpower010 study, which showed that Tecentriq improved disease-free survival by 34% overall when used after initial surgery and chemo for PD-L1-positive NSCLC patients compared to supportive care, and by 57% in patients with high (50% or higher) levels of the biomarker. Roche has a window of opportunity to grow Tecentriq in adjuvant NSCLC unopposed. However, the opening may be short-lived since Merck now has results from the KEYNOTE-091 trial for Keytruda in these patients, which included an all-comer NSCLC population regardless of PD-L1 expression levels. It also included a slightly broader spectrum of NSCLC patients in stages Ib–IIIa versus stage II–IIIa in IMpower010.

Other cancer immunotherapy developers are also doing adjuvant NSCLC studies, and while the results are still months away, they may help oncologists better to grasp the function of immunotherapy in adjuvant NSCLC.

Takeda Reports New Positive Data for Dengue Fever Vaccine TAK-003

Takeda declared that its dengue vaccine candidate, TAK-003, prevented 84% of hospitalized dengue cases and 61% of symptomatic dengue cases, with no vital safety risks identified, in the overall population, including both seropositive and seronegative individuals through 4½ years after vaccination in the pivotal Phase III Tetravalent Immunization against Dengue Efficacy Study trial.

Through 4½ years, TAK-003 showed 84.1% vaccine efficacy against hospitalized dengue, with 85.9% vaccine efficacy in seropositive individuals and 79.3% vaccine efficacy in seronegative individuals. TAK-003 also demonstrated overall vaccine efficacy of 61.2% against virologically-confirmed dengue (VCD), with 64.2% vaccine efficacy in seropositive individuals and 53.5% vaccine efficacy in seronegative individuals. Observations of vaccine efficacy varied by serotype and remained consistent with previously reported results. TAK-003 was generally well-tolerated, and no critical safety risks were recognized. No indication of disease enhancement was detected throughout the 54-month follow-up exploratory analysis.

These new long-term results supplement previously published TIDES trial data that showed the candidate vaccine met its primary endpoint of overall vaccine efficacy against virologically-confirmed dengue, with 80.2% efficacy at 12-months follow-up, as well as all secondary endpoints for which there were a sufficient number of dengue fever cases at 18-months follow-up, including 90.4% vaccine efficacy against hospitalized dengue. While the long-term follow-up for the primary two-dose series has been completed, the TIDES trial remains ongoing to evaluate the safety and effectiveness of a booster dose. The TIDES trial is Takeda’s largest interventional clinical trial, enrolling more than 20,000 healthy children and adolescents (4–16 years of age), across eight dengue-endemic countries, over the past 4½ years.

TAK-003 is undergoing regulatory trials to prevent dengue disease in children and adults in the European Union and select dengue-endemic countries.

FDA Approves Dupilumab for Children 6 Months to 5 Years of Age With Atopic Dermatitis

The US Food and Drug Administration approved Dupixent for children (aged 6 months to 5 years) suffering from moderate-to-severe atopic dermatitis whose disease is not sufficiently controlled with topical prescription therapies. A regulatory filing for the mentioned age group is under inspection by the European Medicines Agency, and submissions to regulatory authorities in additional countries are in process.

Atopic dermatitis is a chronic type II inflammatory skin disease. Eighty-five to ninety percent of patients develop symptoms before age 5, which can continue through adulthood. Symptoms include intense, persistent itch and skin lesions covering much of the body, resulting in skin dryness, cracking, pain, redness or darkening, crusting and oozing, and an increased risk of skin infections. In the United States, more than 75,000 children aged 5 and younger have uncontrolled moderate-to-severe atopic dermatitis and are most in need of new treatment options.

The FDA accessed Dupixent under Priority Review, which is reserved for drugs that significantly improve efficacy or safety in treating severe conditions. The approval is established on data that include a Phase III trial evaluating Dupixent every 4 weeks plus low-potency topical corticosteroids or topical corticosteroids alone. The trial met the primary and secondary endpoints. At 4 months, patients who received Dupixent with topical corticosteroids experienced the following, compared to TCS alone:

• Twenty-eight percent of patients achieved clear or almost clear skin compared to 4% with placebo, the primary endpoint.
• Fifty-three percent achieved 75% or more significant improvement in disease severity from baseline compared to 11% with placebo topical corticosteroids alone, the co-primary endpoint outside the US.
• Forty-eight percent achieved a clinically meaningful reduction in itch compared to 9% with placebo.

The safety profile of Dupixent observed through 4 months in children aged 6 months to 5 years was similar to the safety profile in patients aged ≥6. The long-term safety profile of Dupixent in children aged 6 months to 5 years through 52 weeks was also similar to the safety profile observed in the pivotal trial and consistent with that observed in older patients with atopic dermatitis. Hand-foot-and-mouth disease and skin papilloma were reported in 5% and 2% of Dupixent patients aged 6 months to 5 years, and none of these cases were directed to discontinuation of treatment.

Owkin Bags USD 180 million Alliance from BMS for Cardiovascular Clinical Trials

In one of the latest commercial updates in the pharmaceutical domain, the Bristol Myers Squibb has signed a deal with Owkin to utilize Owkin’s artificial intelligence capabilities to carry out more targeted and efficient clinical trials. The artificial intelligence-powered clinical development platform is intended to cover a wide range of therapeutic candidates for hard-to-treat diseases.

As per the deal, Bristol-Myers Squibb will pay USD 80 million upfront to tap into its expertise. The Owkin will also receive a  BMS’ Series B-1 equity investment and will further receive USD 100 million or more depending on landmarks gained in the current agreement. As per the deal, the companies will focus on improving clinical trial outcomes and identifying biomarkers that can be used to target specific patient subgroups and define the endpoint measures. Both companies intend to find therapies for cardiovascular diseases but utilize AI in other therapeutic areas later. The companies are also expected to disclose further information in the coming months.

A few months back, Owkin agreed to a USD 270 million cancer-focused alliance with Sanofi that has assisted the company’s valuation to touch the USD 1 billion threshold and landed it into the unicorn category.

Roche Secures First EU Approval for Mosunetuzumab for Follicular Lymphoma Treatment

Roche has received conditional marketing authorization from the European Commission (EC) for its relapsed or refractory (R/R) follicular lymphoma (FL) therapy, Lunsumio (mosunetuzumab). Mosunetuzumab is a first-in-class CD20xCD3 T-cell engaging bispecific antibody for adult patients.

The European Commission has approved mosunetuzumab under the Lunsumio trade name for R/R FL. The results of Phase I/II study of mosunetuzumab have formed the basis for the EU to give the regulatory nod. In Phase I/II study, mosunetuzumab demonstrated a complete response rate of 60% and a median progression-free survival of around 18 months when used as a third-line or later therapy. Additionally, the therapy had favorable tolerability in people with heavily pre-treated FL.

Follicular Lymphoma (FL) is one of the most common slow-growing forms of non-Hodgkin’s lymphoma. In Europe, nearly 28,000 people are diagnosed with FL each year. The launch of the mosunetuzumab is expected to improve the overall treatment scenario of FL in the coming years.

100% Clinical Response Rate in all dMMR Rectal Cancer Patients With Neoadjuvant PD-1 Inhibition

A single-agent dostarlimab-gxly (Jemperli) executed a clinical response rate (cCR) of 100% in a small group of patients, i.e., 14 people, suffering from stage II/III locally advanced mismatch repair-deficient (dMMR) rectal cancer, allowing them to avoid chemotherapy, radiation therapy, and surgery at least for the time being.

All 14 patients followed for almost 6 months had complete clinical responses with no evidence of tumor on follow-up MRI. Follow-ups in the cohort ranged from 6 to 25 months, and no patient was reported to have received additional therapy. Four other patients with limited follow-up have preliminary evidence of response, including one clinical complete response. This 6-month course of the PD-1 inhibitor was observed to be well-tolerated, as presented by Andrea Cercek, MD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York City at the American Society of Clinical Oncology (ASCO) annual meeting. The study was presented in the New England Journal of Medicine.

“We observed 100% complete response in the first 14 consecutive patients,” said Cercek. “We noted no grade 3 or 4 adverse events. No patients have required chemotherapy, radiation, or surgery. There has been no disease recurrence during the follow-up period. Longer follow-up is certainly required to establish the durability of this treatment.”

It is noted that almost 5–10% of every rectal cancer is reported to be dMMR, which results in resistance to chemotherapy. Investigators hypothesized that PD-1 blockade might replace chemotherapy, chemotherapy plus radiation, or replace the trimodality approach of chemotherapy, radiation, and surgery. These 14 patients received PD-1 monoclonal antibody dostarlimab at a dosage of 500 mg intravenously every 3 weeks for 6 months, equaling nine total cycles. At baseline and through treatment, patients were closely monitored and assessed for response at 6 weeks, 3 months, and 6 months. At the end of 6 months, a cCR was defined as no evidence of residual tumor on both the digital and endoscopic rectal exams and on the rectal MRI results. 

With high hopes of being a beneficial treatment in rectal cancer, dostarlimab was approved by the FDA in August 2021 for the treatment of patients with dMMR recurrent or advanced solid tumors who have progressed on or following prior therapy and who have no satisfactory treatment options.

FDA Backs Bluebird’s CALD Gene Therapy, Despite Safety Worries

The US FDA seems to have safety concerns about Bluebird Bio’s gene therapy for the rare, fatal cerebral adrenoleukodystrophy (CALD). However, the FDA’s advisors and panel members believe its benefits can outnumber the risks. Agency’s Cellular, Tissue, and Gene Therapies advisory committee members voted a 15 to 0 in favor of the approval of elivaldogene autotemcel – aka eli-cel and Lenti-D – before the FDA’s scheduled decision on the drug this September.

The FDA reviewers mentioned in the briefing documents that several cases of myelodysplastic syndrome (MDS) were found in 4% of children treated with eli-cel, leading to speculation that the panel may have taken a more guarded stance on the therapy. A vote was also formed for the safety data of the therapy, where panelists asked to consider whether data on another of bluebird’s gene therapies called lovo-cel had a bearing on the eli-cel deliberations. Thirteen of them said no, with one abstention and one vote to the contrary.

The main factor that most advisors considered is an overwhelming need for a new treatment option for CALD, a devastating disease caused by mutations in the ABCD1 gene, which allows very-long-chain fatty acids (VLCFAs) to accumulate in the central nervous system, causing severe nerve damage. Eli-cel is designed to upregulate a gene that is very similar to ABCD1 – called ABCD2 – and can compensate for the enzyme deficiency caused by the mutation. The drug has been previously approved in Europe with the name Skysona.